DESC:FIELD OF THE INVENTION-
The present invention relates to a novel botanical composition for diabetes and a method of treatment for diabetes and glucose homeostasis using the tablet. In particular, the present disclosure relates to novel herbal synergy blend of phytoconstituents for diabetes management and glucose homeostasis with improvement in lipid profile, kidney profile. The present disclosure further relates to the fast dissolving tablet with active causality target design statistically with 3 blends of phytoconstituent comprising Mesua ferrea extract, Mimosa Pudika extract, Plumbago indica extract, Boswelia serrata extract, Terminalia Arjuna extract, Saraca asoca extract, Terminalia bellirica extract, Azadirachta Indica extract, Operculina turpethum extract, Senna alexandrina extract and its synergy form as per their own mechanism convert into precise tablet dosage forms for the treatment of diabetes mellitus. Another invention says clinically evaluates for its chronic toxicity study in animal and human clinical trial for the evaluation of diabetes parameters for 60 days.
BACKGROUND OF THE INVENTION
Diabetes is a metabolic disorder, type-2 diabetes may be reversal but in type-1 diabetes, insulin is must require as per medical guidelines. Patients with diabetes deal with either Insulin or OHA. Such a treatment of diabetes is a life-long course of treatment and it’s very expensive. For many patients, insulin injection is an unpleasant process, continue administration of insulin dose degenerate beta cell and can’t produce or secret insulin naturally after taking dose of insulin. Also, the need for daily injections of insulin is hard on the patient's veins. Insulin treatment is costly and it is only a temporary reliever of diabetic symptoms. Continued treatment is necessary in order to control the disease. The antidiabetic drug also resist after some time hence excess or combination dose require for further management of diabetes and its symptoms. Therefore, there is a need for a prime solution as a treatment for diabetes that is permanent, not temporary, safe, and compatible with other dosages and is easily administered to or by the patient. Type II diabetes is the predominant form of diabetes accounting for 90% of cases globally. In type II diabetes, two impairments are found to increase blood glucose levels; impaired insulin action and impaired pancreatic insulin secretion. In addition, the liver also plays a key role in adjusting blood glucose levels via gluconeogenesis in fasting and glucogenolysis in postprandial conditions. In type II diabetes glucogenolysis increases disproportionally which further contribute to elevated blood glucose level. Brain and liver improve glucose homeostasis and gut microbiota plays an important role in glucose utilization and the reabsorption process.
The fact of the survey is about 55% of patients with type-II diabetes mellitus are obese, with the result obesity leads to increased insulin resistance that can develop into diabetes. Further, type-II diabetes mellitus is often associated with obesity, hypertension and dyslipidemia. Additional factors found to be associated with type-II diabetes include Constipation, Ageing, high-fat diets and less active lifestyle and stress is a common factor.
Diabetes is associated with factors which directly contribute to cardiovascular disorders including insulin resistance, dyslipidaemia, atherosclerosis, hypertension, excessive oxidations, endothelial dysfunction, vascular inflammation and growth factors may affect platelet aggregation. Obesity is another risk factor in the development of diabetes. Uncontrolled diabetes causes liver and kidney damage. Glucose is the fuel of our body hence a proper solution for glucose utilization for energy and cell regeneration is a prime need instead glucose inhibition. To keep in mind, with proper management of brain, liver, pancreas, intestine and kidney function, we developed active causality blend accordingly for target action for glucose homeostasis. It is evaluated for chronic toxicity, histopathology and clinical study with human diabetes parameters like Homa-B, Homa-IR, HBa1C, C-Peptide, FBS, PPBS, Lipid profile, kidney profile as per 60 days study.

JP5269894B2, discloses Method for producing fast-dissolving preparation for oral administration, its production, and packaging device.

JP6014044B2, Rapidly dispersible granules, orally disintegrating tablets, and methods discloses Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets.

ES2906115T3, Pharmaceutical composition, treatment methods and uses thereof discloses Empagliflozin for use in a method of protection against the incidence, or delay of the incidence, of doubling of the serum creatinine level accompanied by an eGFR (based on the modification of the diet formula in renal disease (MDRD, <=45 ml/min/1.73 m2 in a patient, wherein said method comprises administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient.

Journal of drug research in ayurvedic sciences, Formulation and evaluation of new herbal nutraceutical tablet for the treatment of diabetes mellitus (Debnath, Bikash, et al.) discloses an herbal nutraceutical tablet was prepared by the wet granulation method. Proximate composition was determined by the Association of Official Analytical Chemists methods. The high-performance liquid chromatography method was used for the estimation of water-soluble vitamins and fat-soluble vitamins. An atomic absorption spectrophotometer was used for analyzing trace elements. Oral glucose tolerance tests and biochemicals were analyzed to assess antihyperglycemic and antihyperlipidemia effects in ob/ob mice.

Journal of Pharmacognosy and Phytochemistry (Vol. 4, Issue 2 (2015) Formulation and phytochemicals characterization of polyherbal (Tinospora cordifolia, Gymnema sylvestre, Pterocarpus marsupium and Acacia arabica) antidiabetic compressed tablet lozenges (Yadav, S., Nand, P., & Gupta, R. K. (2015) The goal of the study was to supply slow release medicament for the treatment of diabetes by formulating polyherbal antidiabetic compressed tablet lozenges. There is still a demand for new dosage forms that act effectively despite various other forms of dosages such as powder, tablets and injectable being available in the market. So the lozenges are the new and innovative way for drug delivery to provide a synergistic effect. Increased retention time of dosage form in the oral cavity is the major advantage of the medicated lozenges. This leads to an increased bioavailability and reduction in gastric irritation and bypass metabolism.

Journal of Pharmaceutical Sciences (Volume 113, Issue 4, April 2024, Pages 1068-1087) Sublingual Administration of Teucrium Polium-Loaded Nanofibers with Ultra-Fast Release in the Treatment of Diabetes Mellitus: In Vitro and In Vivo Evaluation (Polat, Elif Beyzanur, et al.) discloses Teucrium polium (TP) methanolic extract, which has antidiabetic activity and protects the ß-cells of the pancreas, was loaded in polyethylene oxide/sodium alginate nanofibers by electrospinning and administered sublingually to evaluate their effectiveness in type-2 diabetes mellitus (T2DM) by cell culture and in vivo studies.

OBJECTIVE OF INVENTION
The main object of the present invention is to formulate a novel herbal synergy blend for diabetes management and glucose homeostasis with improvement in lipid profile, kidney profile, and liver profile without fluctuation in other hematological parameters. Multiple blends as per their own mechanism convert into precise tablet dosage forms for the treatment of diabetes mellitus. This invention clinically evaluates for its chronic toxicity study in animal and human clinical trial for the evaluation of diabetes parameters for 60 days.
The present invention relates to an herbal composition for the treatment of diabetes, particularly, said composition comprising herbal extract-based composition with a unique combination that is found to provide previously unknown therapeutic or health-promoting benefits in improving the symptoms and complications of diabetes with reduction of OHA and insulin. The compositions of the invention are particularly useful for the treatment of complications associated with type II diabetes and for improving the immune functions in type II diabetes patients and as per clinical evidence 50% reduction in fasting, PPBS and 3.1 HBA1C dropping point found after 60 days of adjuvant therapy.

SUMMARY OF THE INVENTION
The present invention relates to a novel botanical composition for diabetes and a method of treatment for diabetes and glucose homeostasis using the tablet. In particular, the present disclosure relates to novel herbal synergy blend of phytoconstituents for diabetes management and glucose homeostasis with improvement in lipid profile, kidney profile. The present disclosure further relates to the fast dissolving tablet with active causality target design statistically with 3 blends of phytoconstituent comprising Mesua ferrea extract, Mimosa Pudika extract, Plumbago indica extract, Boswelia serrata extract, Terminalia Arjuna extract, Saraca asoca extract, Terminalia bellirica extract, Azadirachta Indica extract, Operculina turpethum extract, Senna alexandrina extract and its synergy form as per their own mechanism convert into precise tablet dosage forms for the treatment of diabetes mellitus. Another invention says clinically evaluates for its chronic toxicity study in animal and human clinical trial for the evaluation of diabetes parameters for 60 days.
DETAILED DESCRIPTION OF THE INVENTION:
Detailed Description of the Invention While this specification concludes with claims particularly pointing out and distinctly claiming that, which is regarded as the invention, it is anticipated that the invention can be more readily understood through reading the following detailed description of the invention and study of the included examples.
The following is a detailed description of embodiments of the present disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.

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

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

The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.
Various terms are used herein. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of.
Among many diseases or disorders of carbohydrate, fat and protein metabolism, diabetes is a serious disorder affecting a large population of the world. It is associated with decreased insulin production or resistance towards its action. Plants have been traditionally used to treat diabetes patients, both insulin-dependent & non-insulin-dependent diabetes. If we convert active constituents with diabetes causality then it will be helpful to increase insulin secretion, enhancing glucose uptake by adipose and muscle tissues, inhibiting glucose absorption from intestine and inhibiting glucose production from hepatocytes. Hence Fast dissolving tablet with active causality target design statistically with 3 blends of Phytochemical/Phytoconstituent and its synergy form and evaluated for its toxicity, histopathology and clinical study. Phytochemicals or Phytoconstituents with high active concentration has a poor characteristic like poor aqueous solubility, compromised permeation, and a low degree of bioavailability. So, the emergence of novel technology and target causality dosage form developed with antidiabetic activity with glucose homeostasis. Tablet compatibility is found good adjuvant with OHA and Insulin. Patient compliance is also good and no side effects are found during the clinical study.
Diabetes mellitus is a syndrome that is characterized by hyperglycemia, change in the metabolism of lipids, carbohydrates, and proteins, and in the long term, with eye, kidney, cardiovascular, and neurological complications. Herbal medicine, phytomedicine or botanical medicine are dealing with causality to reverse chronic disease and its symptomatic relief. Herbal Medicinal is globally accepted in the treatment and prevention mode of diseases including diabetes has a long history compared to conventional medicine. Diabetes is one of the major public health concerns over the world. Diabetes or hyperglycemia is considered to be one of the common public health hazards; optimal control of which is still not possible. Persistent hyperglycemia or uncontrolled diabetes has the potential to cause serious complications such as kidney disease, vision loss, cardiovascular disease, and lower-limb amputations which contributed to morbidity and mortality in diabetes. Active causality target-based herbal (Phytoconstituent’s blend) tablet is designed for glucose homeostasis in Diabetic patients. The ideal characteristic of blend and formulation technology is designed without the chemicals/additives/excipients to minimize side effects. Optimized Evaluation parameters are as under.
• Taste evaluation of the tablet is performed in different volunteers, and the found threshold bitterness concentration is 10 sec. confirmed taste masking.
• Micromeritics properties of each blend include Flow property, Density, Porosity, Carr’s Index improved in Synergy complex than pure form of phytoconstituents.
• Physical characterization by FTIR, DSC and XRPD found that without interaction, key group remain same.
• As per ICH Stability outcome, there are no significant changes found in dosage release, Dissolution, Disintegration, Friability, Hardiness, Weight variation and appearance.
• It will be good option as an anti-diabetic formulation as per Animal toxicity, Histopathology study and Human clinical trial reports, results are attached in tables and figure. As per clinical evidence, even in Type-1 diabetes, it shows reducing dosage of insulin with improvement in HBA1C, C-Peptide and average blood glucose.

In particular, the present disclosure relates to the polyherbal composition comprising of;
a. Mesua ferrea extract, Mimosa Pudika extract, Plumbago indica extract, Boswelia serrata extract, Terminalia Arjuna extract, having 75-85% concentration combined to form blend 1.
b. Saraca asoca extract, Terminalia bellirica extract, Azadirachta Indica extract, having 12-18% concentration combined to form blend 2.
c. Operculina turpethum extract, Senna alexandrina extract, having 5-9% concentration combined to form blend 3.

Tbale 1. Mean values of FPG (fasting plasma glucose) and HbA1C
Duration Mean FPG (mg/dl)
(54.80%) In 60 days Mean % HbA1C
(30%) in 60 days
Baseline 344.70 ± 80.12 10.35 ± 1.95***
Day 30 199.51 ± 30.89 *** NA
Day 60 155.80 ± 31.44*** 7.34 ± 0.97***

Table 2. Fasting and Post Meal Serum Insulin
Parameter Baseline Day 60
Fasting Insulin (µU/ml) 7.88 ± 6.05 13.29 ± 4.53***
Post Meal Insulin (µU/ml) 32.64 ± 14.42 63.10 ± 15.36***

Table 3. Clinical symptoms related diabetes
Clinical symptoms Score Baseline Day 30 Day 60
Polyuria 0 0 0 8 (26.67 %)
1 0 12 (40%) 18 (60)
2 23 (76.67 %) 15 (50%) 4 (13.33)
3 7 (23.33 %) 3 (10%) 0
Polydipsia 0 0 0 9 (30 %)
1 0 12 (40.00 %) 19 (63.33 %)
2 19 (63.33 %) 10 (33.33 %) 2 (6.66)
3 11 (36.66 %) 8 (26.66) 0
Polyphagia 0 0 0 6 (20 %)
1 0 0 22 (73.33 %)
2 9 (30 %) 21 (70 %) 2 (6.66 %)
3 21 (70 %) 9 (30 %) 0

It reduces HBA1C score by 3.0 and 50% Reduction in Fasting and PPBS in 60 days as an adjuvant with glucose homeostasis. C-Peptide and Homa-B Score also improve in 60 days of human clinical trial. As per Chronic toxicity study and histopathology study, without any mortality, there is no abnormalities found in any organ and in hematological parameters. As per 90 Days of Histopathology study as per OECD, CPCSEA Guideline, it has proven safe with mentioned dosage.
Table 4. Total CBC with LIPID, Kidney and Liver function test
Laboratory Investigation Baseline Day 60
Total Leukocyte Count 06.39 ± 02.03 06.55 ± 01.52
Hemoglobin 14.02 ± 02.53 14.59 ± 01.57
Platelets 226.57 ± 75.63 254.62 ± 52.08
Total Cholesterol 180.88 ± 36.25 155.26 ± 28.74
Cholesterol HDL Direct 43.98 ± 10.08 47.92 ± 08.75
Triglycerides 127.66 ± 61.65 123.0 ± 47.56
LDL Cholesterol 115.21 ± 29.09 105.08 ± 23.89
VLDL Cholesterol 26.67 ± 12.09 25.99 ± 07.57
TC/HDL Ratio 04.38 ± 01.90 03.94 ± 00.84
LDL/HDL Ratio 02.95 ± 01.15 02.74 ± 00.61
Serum Calcium 09.12 ± 00.94 09.08 ± 00.55
Serum Uric Acid 05.16 ± 01.14 05.21 ± 01.34
Serum Creatinine 00.86 ± 00.21 00.81 ± 00.11
Bilirubin Total 0.64 ± 0.28 0.68 ± 0.28
Bilirubin Direct 0.24 ± 0.19 0.19 ± 0.08
Bilirubin Indirect 1.23 ± 4.30 0.50 ± 0.23
SGOT 28.44 ± 8.03 26.75 ± 8.11
SGPT 30.14 ± 22.09 23.18 ± 11.01
GGTP 26.53 ± 17.90 21.81 ± 11.85
Total Proteins 7.38 ± 0.45 7.56 ± 0.42
Serum Albumin 4.23 ± 0.31 4.39 ± 0.54

? After treatment there is an increase in the HOMA-B score (0.0121±0.01 to 0.05±0.024) = 75.8 %, baseline to day 60 and there is a reduction in the HOMA-IR score (6.71±6.01 to 5.46±2.45) =1.25 (18%), baseline to day 60 in DM patients.
? As per Physician, In Test Group, physician reported excellent Tolerability of study drugs for 25 (83.33%) and the physician reported Tolerability of study drugs for 5 (16.66%) at the end of the study as per physician assessment.

Histopathology study
Table 5. Force degradation of finished product
Condition Before Average After Average % Degradation
Acid 1N HCl 4 hrs. 455.836667 432.666667 5.08
Base 1 N NAOH 4 hrs 451.553333 437.083333 3.2
Oxidation 30% H2O2 5HRS 816.336667 789.586667 3.27
Thermal (Solid) 800 C 8 HRS 803.583333 731.873333 8.92
Humidity 300 C , 75 + RH, 7 days 862.856667 729.403333 15.46

Table 6. Photo stability of finished blend
Condition Before Average After Average % Degradation
Photo stability (Solid) 24 hrs 471.93 427.537 2.258
Photo stability (Liquid) 24 hrs 471.93 57.11 87.89

Table 7. Physical evaluation parameters
Sr No Parameters Inference
1 Composition of FDT Anti-Diabetic tablet Blend-1 (5 Ingredients) + Blend-2 (3 Ingredients) + Blend-3 (2 Ingredients)


2 Bulk Density (mg/ml) 0.59±0.012
3 Tapped Density (mg/ml) 0.68±0.03
4 Carr’s Index (%) 14.80±2.76
5 Hausner’s ratio 1.14±0.03
6 Angle of Repose (?) 24.91±1.250
7 Zeta Potential (mv) -22.5
8 Particle Size (nm) 98.24
9 Friability 0.912
10 Disintegration Time (Sec) 120±3.60
11 Assay (%) 99.15±0.15
12 In vitro drug release (%) Synergy complex 99.28±0.013
Plain Phytoconstituent 37.88±0.025
Similar marketed formulation 58.31±0.015

,CLAIMS:1. A novel herbal blend of fast dissolving tablet composition for diabetes and glucose homeostasis.
2. The novel herbal blend of fast dissolving tablet composition as claimed in claim 1, wherein herbal synergy blend of phytoconstituents for diabetes management and glucose homeostasis with improvement in lipid profile, kidney profile.
3. The novel herbal blend of fast dissolving tablet composition as claimed in claim 1, wherein fast dissolving tablet with active causality target design statistically with 3 blends of phytoconstituent and its synergy form as per their own mechanism convert into precise tablet dosage forms for the treatment of diabetes mellitus.
4. The novel herbal blend of fast dissolving tablet composition as claimed in claim 1, wherein fast dissolving tablet composition is developed by using 10 phytoconstituents combined in 3 blends comprising of;
a. Mesua ferrea extract, Mimosa Pudika extract, Plumbago indica extract, Boswelia serrata extract, Terminalia Arjuna extract, having 75-85% concentration combined to form blend 1.
b. Saraca asoca extract, Terminalia bellirica extract, Azadirachta Indica extract, having 12-18% concentration combined to form blend 2.
c. Operculina turpethum extract, Senna alexandrina extract, having 5-9% concentration combined to form blend 3.
5. The novel herbal blend of fast dissolving tablet composition as claimed in claim 1, wherein tablet formulation clinically evaluates for its chronic toxicity study in animal and human clinical trial for the evaluation of diabetes parameters for 60 days.
6. The novel herbal blend of fast dissolving tablet composition as claimed in claim 1, wherein micromeritics properties of each blend include Flow property, Density, Porosity, Carr’s Index improved in Synergy complex than pure form of phytoconstituents.