The present invention relates to the field of pharmaceutical sciences. Accordingly, the present invention relates to a process for preparing a pharmaceutical preparation which is to be used for diabetes and diabetic complications treatment. The present invention also provides a method of treating diabetes and diabetic complications using Semolina, triticum and chickpea or the pharmaceutical preparation comprising them and the mixtures thereof. The present process is simple, economical, bio-friendly, and industrially applicable.
Diabetes mellitus is a chronic metabolic disorder of multiple aetiology, characterized by chronic hyperglycemia with disturbance of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. The effect of diabetes mellitus includes long-term damage, dysfunction, and failure of various organs. Diabetes mellitus is usually divided into two major categories:
A chronic condition that affects the way the body processes blood sugar (glucose). With type 2 diabetes, the body either does not produce enough insulin, or it resists insulin. Type 2 diabetes is a lifelong disease that keeps your body from using insulin the way it should. People with type 2 diabetes are said to have insulin resistance.
People who are middle-aged or older are most likely to get this kind of diabetes. It used to be called adult-onset diabetes. But type 2 diabetes also affects kids and teens, mainly because of childhood obesity. Type 2 is the most common type of diabetes. There are about 29 million people in the U.S. with type 2. Another 84 million have prediabetes, meaning their blood sugar (or blood glucose) is high but not high enough to be diabetes yet.
The possible diabetes complications include Cardiovascular disease, Nerve damage, Kidney damage, Eye damage, Foot damage, Skin conditions, Hearing impairment, Alzheimer's disease, depression, and other related disorders.
It is a brainchild of the inventor whose interest is in studying and converting edible material into active targeted therapies and taking care of critical and chronic diseases. That is how the inventor came across Chickpea, Triticum and Semolina and started studying for its Anti Arthritic properties. After performing further research and pre-clinical studies, the inventor observed its anti-arthritis activities that are too significant. Further, it was tested into humans which gives encouraging results in areas where present day therapies are not working. It is unique because it is derived from mixture of Semolina, Triticum and Chickpea and then the biotech process is involved bringing efficacy to the final product.
Chickpea, Semolina and Triticum are very commonly cultivated in various parts of the world. It can be grown in summer as well winter seasons. The fields they are grown in are close to the inventor's premises. The grains were first grinded and pulvaried to powder form and then biotechnologically processed. First use of this mixture was done in March 2000 to study its anti-arthritis properties. Raw material was tested for pesticides content and no contents of the pesticides were found.
The inventor in the present invention have developed a process for preparing the pharmaceutical preparation. The said preparation has shown results in the diabetes and diabetic complications treatment. Accordingly, the present invention provides a method of preparing the pharmaceutical preparation that can be utilized in the treatment of diabetes and diabetic complications. Also provided is the method of treating diabetes and diabetic complications using Semolina, Triticum and Chickpea or the pharmaceutical preparation comprising them and the mixtures thereof.
The main object of the present invention is to provide a process of preparing a pharmaceutical preparation comprising Semolina, triticum and chickpea and the combinations thereof. Another object of the present invention is to provide a process of preparing a pharmaceutical preparation which have applications in the treatment of diabetes and related complications of diabetes.
Another object of the present invention is to provide a method of treating diabetes and related complications of diabetes using Semolina, triticum and chickpea or the pharmaceutical preparation comprising them.
Another object of the present invention is to provide a process which is simple, economical, bio-friendly, and industrially applicable.
The present invention relates to a process for preparing a pharmaceutical preparation which is to be used for diabetes and diabetic complications treatment. The present invention also provides a method of treating diabetes and diabetic complications using Semolina, Triticum and Chickpea or the pharmaceutical preparation. comprising them and the mixtures thereof. The present process is simple, economical, bio-friendly, and industrially applicable.
It is the novel idea by the inventor and used for said diseases. Accordingly, the present invention relates to a process for preparing a pharmaceutical preparation which is to be used in the treatment of Diabetes and diabetic complications. The process comprises of the steps of mixing Triticum, Chickpea and Semolina (obtained by grinding grains) with water and vigorously stirred. The solution is then kept at a temperature 27 ±3° C. and is kept at the temperature for 16 hours, then subjected to further stirring and put into dryers at the temperature 80° C. for 48 hours. The material so obtained is further grinded to obtain very fine powder.
Furthermore, the solution was dried slowly at less than 60 degrees for 48 hours. It demonstrated very good Anti diabetic activity in studies.
According to a preferred embodiment of the present invention, the flours are mixed with distilled water, more preferably double distilled water.
According to another preferred embodiment of the invention, the solution flour is being kept at 27±3° C. for 16±2 hours, subjected to drying at the temperature of 80° C. for 48 hours.
According to another embodiment of the present invention, the solution was dried slowly at less than 60 degrees for 48 hours.
According to another preferred embodiment of the present invention, Triticum, Semolina and chickpea flour and water are mixed in 1:2 ratio respectively. Various means were tried to obtain solids after 2nd step with drying by known methods.
Another embodiment of the present invention provides a method of treating diabetes and diabetic complications using Semolina, Triticum and Chickpea or the pharmaceutical preparation comprising them and the mixtures thereof.
Another embodiment of the present invention provides a use of Semolina, Triticum and Chickpea or the pharmaceutical preparation comprising them and the mixtures thereof in the treatment of diabetes and diabetic complications.
Another embodiment of the present invention provides a method of treating diabetes and diabetic complications using the pharmaceutical preparation which comprises Semolina, Triticum and Chickpea or the mixtures thereof.
Another embodiment of the present invention provides a process of preparing the pharmaceutical preparation wherein the process is simple, economical, bio-friendly, and industrially applicable.
A preferred embodiment of the present invention provides a pharmaceutical preparation of Semolina, Triticum and Chickpea or the mixtures thereof which is be used in the treatment of diabetes and diabetic complications.
The terms “treatment,” “treat,” “treating,” and the like, are meant to include slowing or reversing the progression of a disease or disorder. These terms also include alleviating, ameliorating, attenuating, eliminating, or reducing one or more symptoms of a disease or disorder or condition, even if the disease or disorder or condition is not actually eliminated and even if progression of the disease or disorder or condition is not itself slowed or reversed.
As explained above, the pharmaceutical preparation of the invention is useful in treating or preventing diabetes and related complications of diabetes. The present invention therefore provides pharmaceutical preparation for use in treatment of diabetes and related complications of diabetes. Also provided is a method for treating a patient suffering from diabetes or related complications, which method comprises administering to said patient an effective amount of a pharmaceutical preparation. Further provided is the use of a pharmaceutical preparation, in the manufacture of a medicament for use in treatment of diabetes and related complications of diabetes.
The main embodiment of the present invention is to provide a process of preparing a pharmaceutical preparation, wherein the process comprising the steps of:
In another embodiment of the present invention, flours of Triticum, Chickpea and Semolina are obtained by grinding the grains.
In another embodiment of the present invention, the water is distilled water.
In another embodiment of the present invention, the distilled water is more preferably double distilled water.
In another embodiment of the present invention, Triticum, Semolina and chickpea flour and water are mixed in a ratio of 1:1 to 1:4, preferably, 1:2.
In another embodiment of the present invention, the appropriate temperature of step (b) is in the range of 26 to 32° C.
In another embodiment of the present invention, the appropriate temperature of step (b) is preferably 27±3° C.
In another embodiment of the present invention, the adequate time of step (b) ranges from 15 to 18 hours.
In another embodiment of the present invention, the adequate time of step (b) is 16 hours.
In another embodiment of the present invention, the drying of step (c) is carried out at temperature range of 75 to 85° C., preferably 78 to 80° C.
In another embodiment of the present invention, the temperature of step (c) is 80° C.
In another embodiment of the present invention, the time range of step (c) is 45 to 55 hours, more preferably, 48 hours.
In another embodiment of the present invention, the temperature of step (e) is less than 62° C., more preferably less than 60° C.
In another embodiment of the present invention, the time range of step (e) is 46 to 52 hours, more preferably, 48 hours.
In another embodiment of the present invention, the pharmaceutical preparation has application in the treatment of diabetes and diabetic complications.
Another embodiment of the present invention provides a method of treating diabetes and diabetic complications using Semolina, triticum and chickpea or the pharmaceutical preparation comprising same.
Another embodiment of the present invention provides use of the pharmaceutical preparation as prepared in the process for the treatment of diabetes and diabetic complications.
Yet another embodiment of the present invention provides a process of preparing a pharmaceutical preparation, wherein the process comprising the steps of:
In another embodiment of the present invention, the pharmaceutical preparation has application in the treatment of diabetes and diabetic complications.
Another embodiment of the present invention provides a method of treating diabetes and diabetic complications using Semolina, triticum and chickpea or the pharmaceutical. preparation comprising the same.
Another embodiment of the present invention provides the use of the pharmaceutical preparation as prepared in process for the treatment of diabetes and diabetic complications.
Yet another embodiment of the present invention provides a process of preparing a pharmaceutical preparation, wherein the process comprising the steps of:
The process further comprises the step of mixing Lanolin and Vaseline in the ratio of 1:1 to the pharmaceutical preparation of step (e) in the concentration of 5% to form an ointment.
Another embodiment of the present invention provides an ointment prepared by mixing Lanolin and Vaseline in the ratio of 1:1 to the pharmaceutical preparation in the concentration of 5%.
In another embodiment of the present invention, the pharmaceutical preparation or ointment have application in the treatment of diabetes and diabetic complications.
Another embodiment of the present invention provides a method of treating diabetes and diabetic complications using Semolina, triticum and chickpea or the pharmaceutical preparation or ointment comprising the same.
Another embodiment of the present invention provides use of the pharmaceutical preparation or ointment as prepared for the treatment of diabetes and diabetic complications.
Yet another embodiment of the present invention provides a process of preparing an ointment from the pharmaceutical preparation as claimed in claim 1, wherein the process comprising the steps of:
In another embodiment of the present invention, the ointment is prepared by mixing Lanolin and Vaseline in the ratio of 1:1 to the pharmaceutical preparation in the concentration of 5%, wherein the ointment is applied 0.5 gm daily over the wounds.
In another embodiment of the present invention, the ointment has application in the treatment of diabetes and diabetic complications, wherein the ointment is applied 0.5 gm daily over the wounds.
Another embodiment of the present invention provides a method of treating diabetes and diabetic complications using Semolina, triticum and chickpea or the pharmaceutical preparation or ointment comprising the same.
Another embodiment of the present invention provides the use of the ointment for the treatment of diabetes and diabetic complications, wherein the ointment is applied 0.5 gm daily over the wounds.
The scope of the present invention is illustrated by the following examples as disclosed herein which are not meant to restrict the scope of the invention in any manner whatsoever.
The steps comprising of:
The method comprises of:
Pharmaceutical preparation is an Aldose Reductase Inhibitor as well as Alpha Glucosidase inhibitor. It has given 92.39% inhibition in the said enzymes which are responsible for diabetic complications like Retinopathy, Neuropathy and Muscle wreckage.
Studies were conducted to evaluate pharmaceutical preparation in experimental type 1 diabetes (T1DM).
To compare efficacy of pharmaceutical preparation in comparison to standard hypoglycemic agents as insulin. Effects of pharmaceutical preparation on Plasma Glucose.
Pharmaceutical preparation shown very good efficacy in controlling plasma glucose levels.
Studies were conducted to evaluate pharmaceutical preparation in experimental type 2 diabetes (T2DM).
To compare efficacy of this pharmaceutical preparation in comparison to standard hypoglycemic agent pioglitazone.
Effect of pharmaceutical preparation on Plasma Glucose : pharmaceutical preparation has shown comparable efficacy to pioglitazone.
Effect of pharmaceutical preparation on Glycosylated hemoglobin:
Pharmaceutical preparation has shown comparable efficacy to pioglitazone.
TNF alpha effect on Insulin resistance:
To the liver: stimulating the acute phase response, leading to an increase in C-reactive protein and a number of other mediators. It also induces insulin resistance by promoting serine-phosphorylation of insulin receptor substrate-1 (IRS-1), which impairs insulin signaling. So increase in TNF alpha levels means more insulin resistance. Hence, increase in blood glucose levels.
As pharmaceutical preparation is decreasing TNF alpha levels so less insulin resistance and hence regulation of blood glucose levels.
Test animals: Rats
Strain: Wistar rats
Sex: Female
OECD guidelines for the Testing of Chemicals are periodically reviewed in the light of scientific progress or changing assessment practices. The concept of the up-and-down testing approach was first described by Dixon and Mood. In 1985, Bruce proposed to use an up-and-down procedure (UDP) for the determination of acute toxicity of chemicals. There exist several variations of the up-and-down experimental design for estimating an LD50. This guideline is based on the procedure of Bruce as adopted by ASTM in 1987 and revised in 1990. A study comparing the results obtained with the UDP, the conventional LD50 test and the Fixed Dose Procedure (FDP, OECD Test Guideline 420) was published in 1995.
The test consists of a single ordered dose progression in which animals are dosed, one at a time, at a minimum of 48-hour intervals. The first animal receives a dose a step below the level of the best estimate of the LD50. If the animal survives, the dose for the next animal is increased by [a factor of] 3.2 times the original dose; if it dies, the dose for the next animal is decreased by a similar dose progression. Each animal should be observed carefully for up to 48 hours before making a decision on whether and how much to dose the next animal. That decision is based on the 48-hour survival pattern of all the animals up to that time. A combination of stopping criteria is used to keep the number of animals low while adjusting the dosing pattern to reduce the effect of a poor starting value or low slope. Dosing is stopped when one of these criteria is satisfied, at which time an estimate of the LD50 and a confidence interval are calculated for the test based on the status of all the animals at termination.
Healthy young female rats weighing 110 to 130 grams were selected as the preferred species for conducting the tests in concordance with the paragraph 15 and 16 of OECD TG 425. Healthy young adult nulliparous and nonpregnant female Wistar rats, weighing 110-120 g (10-12 weeks old, at the start of the experiment), were procured.
The animals were randomly selected and kept in their cages for 7 days prior to dosing to allow for acclimatization to the laboratory conditions. The animals were housed one animal per cage and housed at 22° C. (±3° C.) temperature and relative humidity 45% (±5) with natural day/night cycles (approx 12hr dark/light) and supplied with drinking water, ad libitum and standard rat chow (20 g/animal/day). Clean paddy husk bedding was provided to the animals which was changed every 3rd day.
Main test
Since the LD50 value was not known hence the testing directly proceeded to main test (without conducting the limit tests). The volume given was not more than 2 ml/dose/animal/hr. All animals were fasted overnight prior to dose administration. Following the period of fasting, the fasted BW of each animal was determined, and the dose was calculated according to the BW at the time of dose administration. Food was withheld further for a period of 2-3 hours after completing the dose administration. Single animals were dosed in sequence usually at 48 h intervals and observed daily thereafter, for a total of 14 days. Using the default progression factor, doses were calculated using aot425 software as the assumed LD50. Initial dose (175 mg/Kg BW) was selected based on the recommendations of aot425 software and the subsequent doses were calculated with a dose progression factor of 3.2.
Acute Oral Toxicity (OECD Test Guideline 425) Statistical Program
Test/Substance: Pharmaceutical preparation Test type: Main Test
Limit dose (mg/kg): 2000
Assumed LD50 (mg/kg): Default
Assumed sigma (mg/kg): 0.5
Recommended dose progression: 2000, 550, 175, 55, 17.5, 5.5, 1.75
Dose Recommendation: The main test is complete.
Stopping criteria met: 3 at Limit Dose.
Statistical Estimate based on long term outcomes:
The LD50 is greater than 2000 mg/kg.
The pharmaceutical preparations were administered as such.
As recommended by Acute Oral Toxicity—Up-and-Down-Procedure (UDP), the maximum dose 2000 mg/Kg body weight for testing when there is no estimate of the substance's lethality. The range of selected doses included 175, 500, 2000 mg/Kg of body weight.
Body weight
No significant change was observed in individual BW of animals administered the highest allowed dose (2000 mg/kg) for the pharmaceutical preparation.
No mortality was observed in any of the animals and at all the tested doses.
No evident changes for any severe toxicity were observed.
There was no evidence of any toxicity, at the doses under test. This was confirmed by the histopathological studies. No animal showed mortality or morbidity when the tested dose was administered and even after observation for 14 days.
No toxicity was found in studies which proves that pharmaceutical preparation is safe and can be given at high doses. Based on these findings it may be noted that the provided sample of pharmaceutical preparation did not show any mortality at 2000 mg/Kg body weight
Chemistry, manufacturing, and controls data (CMC)
The objective of the study is to evaluate the pharmaceutical preparation in Type-1 Diabetes Mellitus (T1DM) and to compare the efficacy in comparison to standard hypoglycemic agents as insulin.
Experimental model: Streptozotocin (STZ) induced type 1 diabetes (T1DM).
Dose: STZ (45 mg/kg for rats) for T1DM
Route: STZ was administered intraperitoneally (i.p.). Pharmaceutical preparation was administered peroral (p.o.) in three doses.
Volume Administered: Rat—5 ml/kg
Animals: Rats of Wistar or Sprague Dawley strain weighing from 150-200 g of either sex. The animals were housed under optimal laboratory conditions, maintained on a natural (12 h) light and (12 h) dark cycle and have free access to food and water ad libitum. Animals were acclimatized to laboratory conditions before the tests.
Study Design: Animals were divided into 8 groups of 10 animals in each group.
Drugs were administered for 28 days after confirmation of diabetes.
Parameters to be evaluated: The following parameters were evaluated at confirmation of diabetes and after 28 days of treatment.
Statistical analysis
All results were expressed as Mean±SEM. The intergroup variation was measured by one-way analysis of variance (ANOVA) followed by Tukey's test. Statistical significance was considered at P<0.05. The statistical analysis was done using the SPSS Statistical Software version 16 (SPSS Inc. 233 South Wacker Drive, 11th Floor Chicago, IL 60606-6412).
Percentage Change in plasma insulin
Streptozotocin led to progressive increase in Blood glucose levels, Food Intake, Water Intake and Urine output. Streptozotocin produced marked reduction in Body Weight.
Effect of pharmaceutical preparation on Plasma Glucose:
However, plasma glucose levels were significantly reduced at all time points. When we combine pharmaceutical preparation with insulin, pharmaceutical preparation could probably enhance the transportation of insulin to site of action (muscle, liver & adipose tissues) and its consequent binding to insulin receptors so that proper glucose utilization took place. This could be probable reason of reduced systemic insulin levels along with controlled glucose levels. It can be concluded that pharmaceutical preparation is showing insulin sensitizing properties. Thus, pharmaceutical preparation may be demonstrating insulin sensitizing properties like thiazolidinediones (TZDs). TZDs are also shown to reduced plasma insulin levels.
The objective of the study is to evaluate pharmaceutical preparation in Type-2 diabetes mellitus (T2DM) and to compare efficacy of these in comparison to standard hypoglycemic agent pioglitazone.
Experimental model: Streptozotocin-nicotinamide induced Type-2 diabetes (T2DM): Single intraperitoneal injection of nicotinamide and streptozotocin was administered.
Dose: STZ (45 mg/kg for rats)+Nicotinamide (230 mg/kg for rats) for T2DM pharmaceutical preparation (45.90 & 180 mg/kg).
Route: STZ & Nicotinamide were administered intraperitoneally (i.p.). Pharmaceutical preparation & pioglitazone were administered per orally (oral gavage).
Volume Administered: Rat—5 mL/kg
Animals: Rats of Wistar strain weighing from 150-200 g of either sex used for the study. The animals were housed under optimal laboratory conditions, maintained on a natural (12 h) light and (12 h) dark cycle and had free access to food and water ad libitum. Animals were acclimatized to laboratory conditions before the tests.
Study Design: Animals were divided into 6 groups of 5-8 animals in each group:
Pharmaceutical preparation was administered after confirmation of diabetes for 28 days.
Parameters to be evaluated: The following parameters were evaluated after confirmation of diabetes on day 1, 7, 14, 21 and 28 days.
a) Nicotinamide-Streptozotocin led to progressive increase in Blood glucose levels and Glycosylated hemoglobin.
b) Effect of pharmaceutical preparation on Plasma Glucose:
c) Effect of pharmaceutical preparation on Glycosylated hemoglobin:
Experimental animals
Adult female wistar rats weighing 250-300 g were used. All animals were maintained on a 12 h light/dark cycle under standard conditions (25±2° C., 60-70% humidity). They were fed with a commercial standard rat diet and water ad libitum. 7 days prior to the start of the experiment, the ratswere acclimatized to the animal house environment. The experimental protocol was approved by Institutional Animal Ethics Committee (IAEC). All experiments were performed according to the guidelines of Committee for the Purpose of Control and Supervision of Experimentation on Animals (CPCSEA), Government of India.
Preparation of the ointment
Lanolin and Vaseline were mixed in the ratio of 1:1 and pharmaceutical preparation was added in concentration of 5% to prepare the ointment. The wounds of rats were treated with 0.5 g of the ointment daily during the course of treatment
Chemicals and reagents
Pharmaceutical preparation, Cipladine (Povidone iodine 5%) was purchased from CIPLA India. Ltd, Enzyme Linked Immunosorbent Assay (ELISA) kits for TNF-α and IL-6 were obtained from R & D Systems, Minneapolis MN, USA respectively. NF-κβ, NRF-2 and HO-1 sandwich ELISA kit was procured from Elab science, China.
Induction of diabetes
Single intraperitoneal injection of streptozotocin (STZ) freshly prepared in citrate buffer (0.1M, pH4.5), at a concentration of 55 mg/kg body weight, was used to induce experimental hyperglycemia in overnight-fasted rats. Control rats were administered citrate buffer instead. To counter hypoglycaemic shock rats were given glucose (5% w/v) solution during the first 24 h. Blood glucose levels were measured seventy-two hours later, using FreeStyl Optimum Neo® (Abbott Diabetes Care Ltd., UK) digital glucometer from the tail puncture on the tip.
Animals with blood glucose level≥250 mg dL-1 were defined as hyperglycemic and kept under observation or another 7 days. Then, the hyperglycemic rats that maintained high glycemic levels were considered for the in vivo experiments.
Pharmaceutical preparation is administered orally. It is well absorbed. As observed from Human data, it does not contradict nor create negativity with Food and other drugs. All blood parameters remain normal and patients who were having medications for Thyroid, Heart, neuro-defects, rheumatic diseases, Painkillers like (Ultracet, Tramadol), liver diseases were continuing taking this preparation along with their prescribed medication. Usually, no adverse effects were reported. The pharmacokinetics is not altered in patients with renal or liver diseases. The above all information is based on clinical study performed in patients.
Number | Date | Country | Kind |
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202011055968 | Dec 2020 | IN | national |
Filing Document | Filing Date | Country | Kind |
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PCT/IN2021/051193 | 12/22/2021 | WO |