PH12013000212A1 - Ampalaya banaba camote duhat (abcd tablet) - Google Patents

Abstract

ABCD (amplaya, banaba, camote,duhat) is a pioneering herbal drug that combines the four widely used herbals for diabtes. Biologically active constituents found in these plants that have clinically demonstrated hypoglycemic properties, or other actions of potential benefit against diabetes mellitus are summarized and tabulated below to have a better perspective on how the four components can work individually thru their respective mechanisms of action, or together in synergistic combination thru their similarly shared active constituents toward a common goal in controlling the blood glucose level in a diabetic patient.

Description

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HERBAL DRUG AGAINST DIABETES USING .

AMPALAYA, BANABA, CAMOTE, AND DUHAT os

ABCD (ampalaya, banaba, camote, duhat) is a : pioneering herbal drug that combines the four widely - used herbals for diabetes. Biologically active - constituents found in these plants that have clinically - demonstrated hypoglycemic properties, or other actions of potential benefit against diabetes mellitus are summarized and tabulated below to have a better perspective on how the four components can work individually thru their respective mechanisms of action, or together in synergistic combination thru their similarly shared active constituents toward a common goal in controlling the blood glucose level in a diabetic patient

Background of the study:

A thorough and comprehensive introduction for this pioneering herbal drug cannot be done without discussing each individual component and how they could possibly work together synergistically to achieve - optimum and better diabetes control. N

AMPALAYA ;

To date, close to 100 in vivo studies have - demonstrated the blood sugar-lowering effect of - ampalaya. The fruit has also shown the ability to 7 enhance cells’ uptake of glucose to promote insulin release, and to potentiate the effect of insulin. It contains an array of biologically active plant chemicals including treiterpenes, proteins, and steroids. In numerous studies, at least 3 different groups of constituents found in all parts of ampalaya have clinically demonstrated hypoglycemic (blood sugar lowering) properties or other actions of potential benefit against diabetes. These chemicals that lower blood sugar include a mixture of steroidal sapponins known as charantins, insulin-like peptides, and alkaloids. The hypoglycemic effect is more pronounced in the fruit where these chemicals are ound in greater abundance.

Recent experimental investigation by Fernandes et al (2007) with respect to the mechanism of actions of

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M. charantia extract in diabetic rats suggest that it enhances insulin secretion by islets of Langerhans (the :. insulin secreting cells of the pancreas). Thus it reduces - glycogenesis in liver tissue, enhances peripheral glucose 2 po utilization and increases serum protein levels, =

Furthermore, treatment restores the altered histological architecture of the islets of Langerhans. Therefore, the biochemical, pharmacological, and histopathological profiles of ampalaya extract clearly indicate its potential antidiabetic activity and other beneficial effects in amelioration of diabetes-associated complications.

Aside from the already mentioned benefits, an evaluation of the plant’s antilipidemic activity in old obese rats demonstrated significant lowering of cholesterol and triglyceride levels while elevating HDL cholesterol aka good cholesterol levels. Also, the extract lowered serum lipids in diabetic rats suggesting its usefulness in controlling metabolic alterations associated with diabetes.

A more recent study by Bhujbal et al in 2011 evaluated the efficacy of transdermal patches of M.

En . i. 5] charantia in diabetic rats. The patches’ thickness of :. 2cm? roughly equivalent to 10 mg/patch gave a . percentage release of active constituents from the patches of 47.59% in 10% hydroalcoholic phosphate a buffer pH of 7.4 at the end of 6 hours. The transdermal p route gave negligible skin irritation. And in vivo results ) revealed that the patches successfully decreased the i blood sugar level.

Aside from the fruit, the seeds of ampalaya through its active constituents — poplypeptide k and oil isolated from the former showed potent inhibition of [- glucosidase enzyme (79.18% inhibition for polypeptide k, 53.55% inhibition for seed oil) in a study by Ahmad et al (2012). These suggest that both popypeptide k and seed oil from M. charantia are potent potential hypoglycemic agents. A more comprehensive experiment in India by Srivastava et al showed an aqueous powder extract of the fresh unripe whole fruit of M. charantia reduced fasting glucose by 48% comparable to glibenclamide ( a known synthetic antidiabetic drug).

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Ampalaya is contraindicated during pregnancy. Bn

It traditionally has been used as an abortive, and has been documented to have weak uterine stimulant » activity. The plant has also been documented to reduce i. 5 fertility in both males and females and should therefore not be used by those undergoing fertility treatment or - seeking pregnancy. It is also contraindicated in women who are breastfeeding. All parts of ampalaya especially the fruit and seed have demonstrated in numerous in vivo studies that they lower blood sugar levels. As such, it is contraindicated in persons with hypoglycaemia.

Diabetics should check with their physicians before using this plant, and use with caution while monitoring their blood sugar levels regularly as the dosage of hypoglycemic medications and insulin may need adjusting.

BANABA

The second component of our herbal combo is

Banaba (Lagerstroemia speciosa). A plant or tree that grows wild and is widely distributed in the Philippines.

It is also cultivated for its beautiful flowers. As such, its

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I common name Queens Flowers in English is apt for its Es large pink to lavender oblong-obovate-shaped blooms. .

The leaf of banaba is official in the Philippine ol

Pharmacopeia. It is high in corosolic acid or colosolic i. acid, a triterpenoid glucoside, and contains 3 ~ ellagitannins. Namely, lagerstroemin, flosin B, and - reginin A. The plant’s corosolic acid content has been studied for glucose lowering effect. The plant as a whole is rich in tannin which gives it a whole new dimension in as far as having other pharmacologic significance e.g., anticarcinogenic, anti-oxidant, and antibacterial/antiviral/antifungal properties. Tannins have also been reported to exert other physiological effects such as to accelerate blood clotting, reduce blood pressure, decrease serum lipid level, and modulate immune responses.

One of the more popular folkloric uses of banaba is its leaf decoction used in the management of diabetes; also as a diuretic and purgative. For this, a decoction of old leaves and dried fruit (dried from 1-2 weeks) is mixed to 50 grams in a pint (550 ml) of

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En @ boiling water; then taken 4-6 cups daily for diabetes. RS

Old leaves and ripe fruit are preferred which are . believed to have greater glucose lowering effect. A o decoction of 20 grams of old leaves or dried fruit in 100 . ml of water was found to have the equivalent effect of - 6.0 — 7.7 units of insulin.

As mentioned earlier, the ability of this plant to lower blood glucose is attributed to its corosolic content. Studies in mice conducted by Kakuda et al suggests that extracts of L. speciosa have beneficial effects on control of the level of plasma glucose in non- insulin dependent diabetes. For example, hemoglobin

Alc of HbAlc was found to be suppressed at the end of the experiment in the group treate with L. speciosa : extract. Meanwhile, a study by Suzuki et al showed that mice fed with banaba extract also howed a sisgnificant decrease = 65% of the control level in total hepatic lipid contents. These results suggest that banaba has anti- obesity effects as well.

A randomized clinical trial conducted by Judy et al involving patients with type II diabetes assessed the

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Lo fo o antidiabetic activity of an extract of L speciosa leaves Fe standardized to 1% corosolic acid (Glucosol). Findings . revealed that at daily doses of 32 and 48 mg, a y significant decrease in blood glucose levels was = observed in diabetic patients after only two weeks of -

Glucosol intake.

According to the Philippine Pharmacopoeia 2004, pregnant women, nursing mothers, and children : should avoid intake of banaba products. And that patients with hypoglycaemia should also avoid taking any prparations of L. speciosa leaf. ]

CAMOTE

Ipomoea batatas or camote 1s sweet potato in

English. It is cultivated extensively throughout the

Philippines as a cheap source of carbohydrates especially among the rural and urban poor. It has a higher nutritional value than the common potato. A good source of vitamin A, B, C, iron. Calcium, and phosphorus. It is high in complex carbohydrates and ] dietary fiber. The leafy tops are eaten as vegetables, a component of many traditional cuisines. Although

» technically a root crop of agricultural importance, it is - the leaves that holds medicinal value. They have a high . content of polyphenolics — anthocyanins and phenolic - acids. With at least 15 biologically active anthocyanins ~ with medicinal value. -

Phytochemical screening conducted by -

Pochapski et al on the crude extract fractions of

I.batatas leaves yielded positive for several phytochemical classes — treterpenes/steroids, alkaloids, flavonoids, saponins, tannins, phenolic acids to name a few. Numerous other compounds have also been isolated of varying significance. Steed and Traong conducted a study which included quantifying the anthocyanin and phenolic content of purees of purple- fleshed I. batatas. A study by Chandrika et al quantified the carotenoid and lutein content of selected green leafy vegetables that were popular in Sri Lanka. Camote leaves had the highest beta carotene content (743.9 + 33.0 ug/g/dry wt) while the lutein content was also found to be relatively high (1685.8 + 101.7 ug/g/dry oo : 10

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Camote leaves have traditionally been used for Fe diabetes by eating the top after being cooked by . blanching or as garnishing in fish stew. Hot water - infusion of the whole plant is also used in southwest on

Nigeria. The crushed leaves are applied to boils and . ] acne while the boiled roots are eaten for diarrhea. The tea from scalded or dried slices of the tubers is used to ally thirst in China.

Severa studies have explored the activity of

Ipomoea batatas against diabetes. In a study by Li et al after obtaining the optimal extraction parameters of flavonoids from Ipomoea batatas leaves, the flavonoid- rich preparations was used to treat alloxan-induced diabetic mice. Results showed that treatment for 28 days significantly decreased fasting blood glucose levels. In addition, there was also an observed significant decrease in total cholesterol and triglycerides, while increasing body weight and serum

HDL (good cholesterol). Optimal dose was determined at 100 mg/kg body weight.

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A study by Ozaki et al revealed that continuous . administration of an arabinogalactan protein isolated . from the tuberous cortex of the white skinned camote to > experimental mice significantly lowered the fasting on plasma glucose. Oki et al followed up on this study with - a separate investigation on the protein’s effect on - hyperglycemia in mice. Their findings include significantly decreased plasma glucose levels after an oral glucose tolerance test. As well as an increae in : insulin sensitivity based on an insulin tolerance test.

This indicates that the hypoglycemic activity of the protein maybe due to a reduction in insulin resistance. i

A study by Niwa et al also observed significant decreases in fasting blood glucose. As well as HbAlc levels in streptozotocin-induced diabetic rats fed with powdered Ipomoea batatas for 2 months. On the other hand, based on their analysis of markers of anti-oxidant activity including histological studies of the pancreas, they proposed that the hypoglycemic effects of Ipomoea batatas result from the suppression of oxidative stress and pro inflammatory cytokine production, along with os an improvement of pancreatic B-cell mass. A systematic - review and meta analysis of the effects of herbal supplements on glycemic control in type II diabetes was : conducted by Suksomboon et al. Based on the current - evidence, they concluded that supplementation wth -

Ipomoea batatas among other medicinal plants may - improve glycemic control in patients with type II diabetes.

Similar to other herbals, camote has other biologic activities as well. Other researchers have focused on its anti-oxidant, anti-inflammatory, hepatoprotective, antineoplastic, and antilipidemic properties. One study worth mentioning here is the one by Park et al regarding the anti-oxidant activity of anthocyanins from I. batatas. Much evidence showed that the latter can protect against the adverse effects 1 brought about by the oxidation lipids usually from a high cholesterol diet. Included in their findings is the in vitro activity of ethanol and eater extracts from purple

Ipomoea batatas against atherosclerosis secondary to the oxidation of lipids. In addition, they also found that

- it protected against protein glycation, which is a known - risk factor for diabetes mellitus. Whereas, Miyazaki et po

Ln al have shown that the ability of anthocyanins from o

Ipomoea batatas to suppress atherosclerotic lesions and ; oxidative stress markers in mice occurs independently - of changes in cholesterol and lipid levels.

A randomized, cross over clinical trial by Chen et al on 16 healthy adults was able to show that the intake or consumption of purple Jpomoea batatas leaves decreased lipid peroxidation and DNA damage. Their result suggests that the polyphenols in the camote leaves were bioavailable as evidenced by an increase in total phenol excretion after 2 weeks of the treatment period.

Also, low density lipoprotein (LDL) lag time and glutathione concentration in erythrocytes after the treatment period was significantly enhanced by 15.0 and 33.3%, respectively. These findings indicate the potential of camote leaves to increase anti-oxidant defense and decrease oxidative stress in humans.

Finally, a randomized clinical trial conducted by

Ludvik et al observed 27 patients with type II diabetes bo who received 4 grams of Ipomoea batatas leaves for 5 - months, and 34 patients who received placebo. The fo

Ln study’s findings confirm the beneficial effects of -

Ipomoea batatas on glucose and HbAlc control in patients with type II diabetes after 5 months of follow - up. Also observed was improvement in insulin = sensitivity, along with increased levels of adiponectin and a decrease in fibrinogen. These results suggest that

Ipomoea batatas works as a natural insulin sensitizer with potential anti-atherogenic properties.

No known contraindications regarding the consumption of camote root crop. However, the : leaf/tops as seen to have hypoglycemic effect is therefore, recommended for known and suspected diabetics especially those under hypoglycemic medications to take the necessary precautions in adjusting their doses with the advice of their physicians.

DUHAT

Duhat or Syzygium cumini is a smooth tree about 8 to 15 meters high. It is found throughout the

Philippines. Of special interest is the oval dark purple or

- bo nearly black fruit. It is luscious, fleshy, and edible with - a sweet astringent taste containing a single large seed. por a

Thus it is also known as “black plum” in English. It’s ~ one of the more popular fruits in the Philippines - especially during summer. The ripe fruit is eaten - . outright. The juice from the fruit can be made into wine + or vinegar. And is a good source of calcium and iron.

The fruit, leaves, and tree bark are of medicinal importance. Recent phytochemical screening conducted by Soni et al on the ethanol extract from the leaves of S. cumini in India yielded positive for glycosides, tannins, phenolic compounds, and carbohydrates. While an earlier screening by Ugbabe et al on the methanol extract from the leaves in Nigeria yielded positive for flavonoids, saponins, terpenes, sterols, tannins and phenols; as well as balsams, resins, carbohydrates, and volatile oils. Whereas the methanol extract from the stem/bark yielded positive for flavonoids, saponins, terpenes, sterols, tannins, phlobotannins, and phenols; as well as balsam, resins, and carbohydrates. The S. cumini bark 1s official in the Philippine Pharmacopoeia.

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A quantitative mineral analysis of the fruit was - conducted by Benherial an Arumughan. And their result showed that calcium was abundant in all fruit parts and ; extracts. In the fruit pulp total phenolics were ) determined at 3.9 = 0.5 g/kg; anthocyanins 1.34 = 0.2 - g/kg, while flavonoid contents at 0.07 £0.04 g/kg. -

Whereas, kernel and seed coat contained 9.0 + 0.07 g/kg and 8.1 = 0.8 g/kg total phenolics, respectively.

Traditionally in the Philippines, duhat has had its share of folkloric uses. The decoction of the bark is used for dysentery; as mouthwash/gargle for oral ulcers and gingivitis; as astringent wash for external wounds, and as enema. The ripe fruit is astringent and considered as efficient remedy for diabetes. Decoction of leaves and bark also used for diabetes, but the ripe fruit is considered the best. If in season (summer) a person with diabetes may reportedly eat the ripe fruit at leisure.

Quisumbing cites Guerrero who states that the pulverized dried seeds are also useful in diabetes.

Laboratory and nonclinical studies on the biologic acitivity of duhat have been done especially

. RY oo with regard to its anti-oxidant, anti-inflammatory, Ea antimicrobial, and antidiabetic effects.

Several studies . have investigated the anti-oxidant properties of duhat . which evaluated the activity based on the phenolic - ]

contents of the seeds and leaves.

One study worth o mentioning here is the one by Abdalla et al which assessed the effect of the aqueous seed extract on oxidative stress induced by methyl mercury in neonatal rats.

Methyl mercury has been known to be a toxic environmental pollutant which can cause dysfunction in many cell types.

In this study they determined that the seed extract was able to revert the toxic effects of methyl mercury in the animal subjects; as evident in the better levels of certain enzymes in the brain, liver, and kidney.

The study attributed this to the main compound present in the aqueous seed extract, namely gallic acid, chlorogenic acid, and ratin.

These are all phenolic compounds.

Other studies isolated tannins from the fruit and suggested the use of the fruit as a significant source of natural anti-oxidants.

They also showed a significant ] correlation between extract concentration and

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Co percentage of free radical inhibition or lipid . peroxidation. Authors suggest the anti-oxidant property - of the fruit skin may come in part from the anti-oxidant ; vitamins, phenolics, tannins, and anthocyanins present - in the fruit. -

The antimicrobial biologic activity of duhat has " also been evaluated. Of particular interest here is the antibacterial property experimented by Sharma et al wherein, they screened several medicinal plants in vitro for vibriocidal activity against 12 isolates of Vibrio cholera. They found that the water, acetone, and ethanol extracts of duhat exhibited one of the highest vibriocidal activity against most of the strains tested. They study concludes that among the medicinal plants screened, S. cumini has the potential to be a broad spectrum vibriocidal agent. Hofling et al evaluated the antifungal activity of selected plant extracts against different species of Candida. Included in their study was the assessment of the dichloromethane and methanol extracts from the seeds of S. cumini. Both showed strong antifungal activity against the tested strains.

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Especially the methanol extract which consistently and He significantly inhibited all strains of Candida used in the . study. The study suggests that S. cumini is a potential - source of anticandidal therapeutic agent. a

Several studies have probed into the antidiabetic . activity of duhat particularly due to its popular use in traditional medicine systems in the treatment of diabetes. In a study by Shinde et al, they demonstrated the seed kernel extracts to exhibit [I-glucosidase inhibitory activity in vitro, a property which decreases glucose absorption from the digestive tract. Similarly, different studies have shown the inhibitory activity of duhat seed extracts on pancreatic [J-amylase in vitro which may also be beneficial to the management of diabetes. In addition, studies by Bopp et al and De Bona et al have shown inhibitory effect in vitro of S. cumini leaf extracts on adenosine deaminase activity, and improve antioxidant status in the serum of diabetic : patients. Both of which are associated with improving blood sugar control and mitigating long term complications of diabetes.

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Though a number of studies as mentioned above - have provided evidence suggestive of antidiabetic - activity of S. cumini, Texeira et al have conducted : studies that indicate the absence of antidiabetic activity - of S. cumini. In a randomized, parallel, placebo - controlld trial employing a tea prepared from S. cumini . leaves, no significant antihyperglycemic effect was observed in 30 nondiabetic, young volunteers who took a blood glucose tolerance test, whereas, in a randomized double blind, double dummy controlled trial on patients with type II diabetes, Texeira et al also found no significant effect on the fasting blood glucose of patients who received treatment with the tea prepared from S. cumini leaves nor from placebo. They report 27 patients who were followed for 28 days. After which, the study found that the fasting blood glucose levels significantly decreased in the group which received an oral hypoglycemic (Glyburide); while no such effect was found in groups that received S. cumini tea or placebo.

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Detailed Description: .

The active ingredients of the inventions are: he

Ampalaya leaf powder - 2.25kg

Banaba leaf powder - 2.25kg gi

Camote leaf powder - 0.25kg

Duhat leaf powder - 0.25kg

Cornstarch - 0.20kg

Lactose Monohydrate - 0.20kg

The ingredients are passed through stainless steel screen mesh #30. Then loaded into Sigma-Bio mixer and mixed for 15-20minutes. In a separate suitable stainless steel container mix cornstarch 0.96kg to Purified water 1.5L, disperse completely the cornstarch with continuous mixing. Into a steam jacketed kettle, purified water 3.6 Liters is heated up to 90-95° . Add the cornstarch and water mixture ! to the heated water gradually with continuous mixing until a uniform translucent paste is obtained. Wet the ingredients mixture from the bio mixer by gradually on

Jon adding the translucent paste (water and cornstarch), . with continuous mixing until a uniform damp mass is . obtained. Pass the wet mass through stainless steel . screen mesh #4, and load into the Fluid Bed Dryer. Dry ) the bulk mass at 60°c until a moisture content 2-4% is - obtained. -

Check the relative humidity and temperature of the room. Ensure that the relative humidity should not be more than 55%, and the temperature should not be more than 28°. Resize the dried granules using Fitzmill fitted with stainless steel screen mesh #20, and load into the V-blender, and mix for 15 minutes. Pass the mixture through stainless steel screen mesh #80; add magnesium stearate 0.04kg or 40gms. Premix into a 0.5kg portion of the bulk mixture using a suitable P. E (polyethylene) bag and mix. Load into the V-blender and mix for 5 minutes.

The bulk mixture is compressed into tablets under specified parameters.

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1. Check color and consistency of bulk powder- .

green to dark green granules with characteristics . odor. o 2. Check the punches and dies of the tableting . machine. o

3. Check the following during -

compression: - Tablet weight ; 640 mg + 5% - Tablet thickness 6.70 to 7.20 mm - Tablet length ; 15.5 mm to 15.90 mm - Friability : not more than 1.0%

: - Moisture content : 2- : 4% - Enable hardness 7- 15kgb :

= - Disintegration test: . not more than 30 pe

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Claims (4)

{ Co fo : CLAIMS En

1. A Pharmaceutical composition containing: .

a. Ampalaya leaf powder - 225mg or 45% . by volume as active ingredients .

b. Banaba leaf powder - 225mg or 45% - by volume :

C. Camote leaf powder - 25mg or 5% by i volume ingredients d. Dubhat leaf powder - 25mg or 5% by | volume as active ingredients Said composition is distributed in a suitable vehicle to be formulated into a tablet.

2. A Pharmaceutical formulation/composition according to claim 1 wherein 14-18% by weight of cornstarch was used.

3. A Pharmaceutical formulation/composition according to claim 1 wherein 2-3% by weight of : Lactose monohydrate was used.

4 A Pharmaceutical formulation/composition according to claim 1 wherein 8% by weight of magnesium stearate was used.