FIELD OF INVENTION
The present invention relates to the field of management of kidney disorders. More specifically, the invention relates to an herbal extract for the treatment of renal calculi and the process of preparation of an herbal formulation comprising such herbal extract.
BACKGROUND OF THE INVENTION
Urolithiasis or renal calculi is a process of formation of stones in the urinary tract i.e. in the kidney, bladder, and/or ureter. Kidney stones are one of the most painful urological disorders. The term nephrolithiasis or “renal calculus” refers to stones located in the kidney. Kidney stones affect up to about 1% - 15% of the population.
Urolithiasis takes place with nucleation, aggregation and retention of salts in urine wherein salts bind to the colloid matrices in the kidney and urinary tract. In this process, aggregates of tiny crystals of urinary salts are formed as kidney stones or renal calculi. Some of the factors/promoters causing renal calculi are super saturation of urine with stone forming salts such as Calcium oxalate, calcium phosphate and uric acid. Other factors include nutritional and environmental factors like dehydration, excess animal protein in diet, etc. The salts whose balance or levels act as inhibitors of stone formation include levels of citrate, pyrophosphate, magnesium, zinc, glycoprotein, and glycosaminoglycan. Moreover, decrease in urinary pH, increase in the crystalloid level and/or fall in colloid level, change in urinary magnesium/calcium ratio, infection of the urinary tract, urinary stasis, decreased urinary output of citrate, vitamin deficiency, hyperparathyroidism and prolonged immobilization are additional factors. These
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metabolic abnormalities result in super saturation of urine and hence stone forming salt ions such as calcium oxalate, spontaneously join together to form solid crystals. These tiny crystals stick together forming large aggregates which get retained in the kidney and continue to grow larger. If the stones have grown to a critical size such as 5-10mm in diameter, then passage through kidneys to ureters may get obstructed leading to renal colic, hydronephrosis, urinary tract infection, postrenal azotemia.
In case of renal calculi of one of the kidneys, compensatory hypertrophy due to over exertion can be induced in the other healthy kidney as well. Management of renal calculi is decided on the basis of ultrasound scanning of the kidneys and urinary tract and analyzing the size and location of the calculi. Small sized calculi are expected to flush out with intake of plenty of water. This is usually supported with prescription of diuretics such as thiazides, potassium citrate etc., for increasing urination and pain killers to relieve the discomfort associated with passing out of the calculus. Renal calculi are also treated using extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy or uteroscopy. Due to the difficulty in flushing out larger sized calculi, ESWL is used to break it down so that they can be flushed out in the urine. However, ESWL is associated with side effects like moderate pain, blood in urine, bruising of back or abdomen by the sound waves, bleeding around the kidney and adjacent organs etc. Further, ESWL is not very successful in removal of large stones which are subsequently removed by surgery. Surgical procedures though effective in treatment involve high cost and lead to other side effects of urinary tract infection and are not patient compliance.
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Drugs known as alpha-blockers relax the walls of the ureter. This widens the passage so a stone can pass through more easily. Side effects are generally mild and may include headache or dizziness. Other types of medications can help in preventing new stones formation. Allopurinol (Zyloprim, Aloprim) is used to reduce uric acid levels in the blood and therefore it works as a medicine to keep the urine alkaline. In addition, there are several other herbal medicaments which are available to treat renal calculi.
CN101658644B discloses an internal administration medicament for treating urolithiasis disease, which consists of the following Chinese medicinal herb raw materials: chicken gizzard membrane; sstragalus root; saltpeter; red paeonia; borax; lygodium japonicum; desmodium; corn silk; raw hawthorn; and costustoot.
CN101618110B discloses application of a Chinese medicinal composition in preparing a medicament for treating urinary calculi. The Chinese medicinal composition consists astragalus root, steatite, selfheal, and the like. The medicinal composition has the efficacies of promoting qi transformation, promoting diuresis and softening hardness to dissipate stagnation.
RU2445970C1 discloses the herbal agent for treating and preventing urinary stone disease, containing bearberry leaves, common madder roots and rhizomes, bottle brush herb, knotgrass herb, rose hip, peppermint leaves, Indian kidney tea leaves or birch leaves, horseheal roots and rhizomes and wild strawberry leaves in certain proportions.
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In the view of limitations and drawbacks of the existing therapies, it is continuously desirable to develop the therapies which exhibit minimum or no side effects, while being readily available and cost-effective and show excellent efficacy in maintain overall health of the patient by preventing and treating stone formation. The above-described deficiencies of existing medicaments are merely intended to provide an overview of some of the problems of existing medicines, and are not intended to be exhaustive.
Research is always being carried for new developments which will give more efficient medicaments than that of existing ones, at the same time it will be less costly and simple to produce.
The present invention provides an effective herbal composition to manage renal calculi. Further we have not come across any reference which teaches or demonstrates herbal medicaments compositions comprising of Euphorbia hirta.
OBJECT OF THE INVENTION
The main object of the present invention is to provide an herbal extract, for prevention and treatment of renal calculi comprising solvent extracts from Euphorbia hirta.
A further object of the present invention is to provide an herbal extract, for prevention and treatment of renal calculi, which is efficacious, safe, and devoid of side effects.
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Another object of the present invention is to provide a process of preparation of an herbal formulation comprising solvent extracts from Euphorbia hirta.
SUMMARY OF INVENTION
Thus according to the basic aspect of the present invention, there is provided an herbal extract for the prevention and treatment of renal calculi, comprising therapeutically effective amount of solvent extract from Euphorbia hirta.
In one of the aspect of the present invention, the herbal extract comprises of about 2%-20% (w/v) of Euphorbia hirta.
One aspect of the present invention provides a process of preparation of an herbal formulation comprising solvent extracts from Euphorbia hirta, for treatment of renal calculi.
The process of preparation of the herbal formulation comprising the steps of:
i. washing, drying and grinding of Euphorbia hirta to get powdered form of herb;
ii. taking the powdered herb from step (i) in a solvent in a ratio of 1:20 (w/v) to get a solution; iii. extraction of the solution obtained in step (ii) at a temperature of 25°C- 45°C to get an extract;
iv. concentrating the extract obtained from step (III), followed by drying of extracts at 50°C- 60°C using rotary evaporator to get dried powder of Euphorbia hirta; and
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v. adding pharmaceutically acceptable excipients to the dried extract obtained from step (IV) to get an herbal formulation.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is thus directed to an herbal composition effective for prevention and treatment of renal calculi, comprising therapeutically effective amount of solvent extracts of Euphorbia hirta.
Before the present invention is described, it is to be understood that unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Further, it is to be understood that the present invention is not limited to the methodologies and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described, as these may vary within the specification indicated. Unless stated to the contrary, any use of the words such as "including," "containing," "comprising," "having' and the like, means "including without limitation" and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it. Embodiments of the invention are not mutually exclusive, but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth the appended claims. Further the terms disclosed embodiments are merely exemplary methods of the
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invention, which may be embodied in various forms. It is also to be understood that the terms "a", "an", "the" and like are words for the sake of convenience and are not to be construed as limiting terms. It is also understood that the terms "washing", grinding", "drying", "extraction" used herein intend to cover all kinds of conventional methods used for the said purpose carried out at room temperature unless specified particularly herein.
The herbal medicament of the present invention is simple, natural, attractive and convenient to use. The preparation method for herbal medicament is simple and the effect is excellent; the price is low. The herbal medicament of the present invention is useful in the treatment of renal calculi.
In an important embodiment of the present invention, the herbal composition of the present invention comprises of about 2% to 20% (w/v) of Euphorbia hirta.
In a preferred embodiment, parts of Euphorbia hirta includes roots, while any of plant parts or whole plant may also be used for preparing said herbal composition for treatment of renal calculi.
Euphorbia hirta also called as Asthma Weed, has traditionally been used in Asia to treat bronchitis asthma and laryngeal spasm, though in modern herbalism it is more used in the treatment of intestinal amoebic dysentery. The plant is anodyne, antipruritic, carminative, depurative, diuretic, febrifuge, galactogogue, purgative and vermifuge. The
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stem, taken internally, is famed as a treatment for asthma, bronchitis and various other lung complaints. It is usually used in combination with other anti-asthma herbs such as Grindelia camporum and Lobelia inflate. It is also used to treat intestinal amoebic dysentery. The whole plant is decocted and used in the treatment of athlete's foot, dysentery, enteritis and skin conditions. It has been used in the treatment of syphilis. The sap is applied to warts in order to destroy them.
For the purpose stated in present disclosure, parts of Euphorbia hirta, were collected from Udaipur district of Rajasthan, India.
In an embodiment, the herbal composition of the present invention optionally contains at least one pharmaceutically acceptable excipient including without limitation buffering agent, preservatives, bulking agent, binder, disintegrant, suspending agent, encapsulating materials, chelating agent, a glidant, a flavouring agent, a colouring agent, a tonicity agent, and a co-solvent, and like.
In yet another embodiment, the formulation further comprises of at least one of pharmaceutically acceptable excipients, selected from the group consisting of a buffering agent, wherein a buffering agent may include but not limited to mineral buffers such as Phosphate, Tris, Borate, Citrate, Glycine, etc. and organic buffers like glycine and other biological buffers.
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In another embodiment, the formulation may comprise of at least one of the pharmaceutically acceptable excipients, selected from the group consisting of a preservative which may include but not limited to, antioxidants, T-50 vitamin E oil, rosemary oil extract, anti-microbials and like.
In an embodiment, the formulation may comprise of at least one of the pharmaceutically acceptable excipients, selected from the group consisting of a bulking agent which may include but not limited to, fibers, including pectin, psyllium seed, and guar gum, that provide laxative properties and like.
In yet another embodiment, the formulation may comprise of at least one of the pharmaceutically acceptable excipients, selected from the group consisting of a binder, which may include but not limited to, natural binders like acacia, gelatin, alginic acid, cellulose or commonly used binders like starch 1500, methocel, walocel HM and like.
In another embodiment, the formulation may further comprise of at least one of the pharmaceutically acceptable excipients, selected from the group consisting of a disintegrant, which may include but not limited to, pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone, and like
In yet another embodiment the formulation may further comprises of at least one of the pharmaceutically acceptable excipients, selected from the group consisting of a suspending agent, which may include but not limited to, alginates, methylcellulose,
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hydroxyethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, and like.
One skilled in the art will appreciate that suitable formulations are dependent on the form of delivery to be employed and all such forms are contemplated by the present invention.
In an embodiment, the herbal composition of the present invention may also be formulated in different dosage forms for oral, parenteral administration.
In an embodiment, the herbal composition of the present invention may be formulated in dosage forms for oral administration selected from liquid, granules, powder, capsule, tablets, bolus, or like.
An exemplary process for preparing the herbal composition of the present invention is described below.
In an important embodiment, the herbal formulation of the present invention, for treatment of renal calculi, is prepared by the process comprising the steps of:
i. washing, drying and grinding of Euphorbia hirta to get powdered form of herb;
ii. taking the powdered herb from step (i) in a solvent in a ratio of 1:20 (w/v) to get a solution;
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iii. extraction of the solution obtained in step (ii) at a temperature of 25°C- 45°C to get an extract;
iv. concentrating the extract obtained from step (III), followed by drying of extracts at 50°C- 60°C using rotary evaporator to get dried powder of Euphorbia hirta; and
adding pharmaceutically acceptable excipients to the dried extract obtained from step (IV) to get an herbal formulation.
EXAMPLE 1
The process of preparation of the herbal formulation comprising the steps of:
i. washing, drying and grinding of Euphorbia hirta to get powdered form of herb;
ii. taking the powdered herb from step (i) in a solvent in a ratio of 1:20 (w/v) to get a solution; iii. extraction of the solution obtained in step (ii) at a temperature of 25°C- 45°C to get an extract;
iv. concentrating the extract obtained from step (III), followed by drying of extracts at 50°C- 60°C using rotary evaporator to get dried powder of Euphorbia hirta; and
v. adding pharmaceutically acceptable excipients to the dried extract obtained from step (IV) to get an herbal formulation.
EXAMPLE 2
The efficacy of the herbal composition was tested in animal model of urolithiasis. Healthy male wistar rats (180-250 g, 6-8-week age) were selected for the study. All groups received regular rat food ad libitum. Except group I all animals received 0.75% v/v ethylene glycol in drinking water ad libitum throughout study period. Group I
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received drinking water ad libitum. Group III received standard antiurolithiatic drug Cystone (750 mg/kg) once daily p.o up to 28th day. Group IV received herbal composition orally daily throughout the study period. The treatment groups and experimental protocol are given in detail below:
Group I: Normal Control
Group II: Ethylene Glycol (EG) Control
Group III: EG + Cystone – 750 mg/kg.
Group IV: EG + Herbal extract
Various biological parameters like BUN, creatinine, oxalate, phosphate, uric acid, citrate, and magnesium content in the urine were analyzed. The catalase, and MDA content in kidney homogenate were also determined.
Significantly (p<0.05) higher urinary oxalate levels were reported in model control Group II animals as compared to the normal control animals of Group I. Pre-treatment with standard drug Cystone showed significant reduction in urinary oxalate levels. Treatment with herbal composition also showed a very significant reduction in urinary oxalate levels in comparison to lithiatic group.
Kidney homogenate from ethylene glycol exclusive group demonstrated significantly high oxalate levels as compared to the normal group. Pre-treatment with standard drug resulted in significant drop and the herbal composition also demonstrated quite significant reduction in oxalate levels in kidney homogenate in comparison to lithiatic group.
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Significant (p<0.05) increase in urinary inorganic phosphate levels in model control group as compared to normal control animals was found. The levels reduced after treatment, reduction in standard drug and in case of herbal composition, in comparison to lithiatic group.
Citrate levels were found to be significantly lower (p<0.05) in model control animals as compared to normal group I of animals. Standard drug showed significant increase in urinary citrate levels and pre-treatment with herbal composition demonstrated significantly higher citrate levels when compared to the lithiatic group.
Significant (p<0.05) increase in serum creatinine levels as compared to normal control animals was found in model control group. Creatinine levels in serum were found to be significantly decreased on administration of standard drug and also in case of herbal composition as compared to the lithiatic group.
Significant (p<0.05) decline was observed in urinary magnesium levels in the group II as compared to normal control group I. Significant increase was observed in treatment group with standard drug and with herbal composition when compared to the lithiatic group.
Pre-treatment with herbal composition showed statistically significant decline in BUN levels. Treatment with standard drug showed a decline as compared to lithiatic group.
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Antioxidant catalase levels decreased in kidney homogenate of ethylene glycol alone group which was significant from normal control. Pre-treatment with standard drug and with herbal composition significantly increased catalase levels by as compared to the lithiatic group.
Lipid peroxidation marker MDA was found to be significantly reduced in herbal composition and the reduction in the standard drug treated group as compared to lithiatic group.
From above, it is evident that the herbal composition has excellent anti-urolithiatic activity. The administration of herbal composition resulted in marked improvement of urinary biochemical markers. The composition was also found to have superb anti-oxidant potential as demonstrated by significant increase in catalase levels as well as decrease in MDA content in kidney homogenate.
From the present invention as described above, it is to be understood that this invention is not limited to particular methodologies and materials described, as these may vary as per the person skilled in the art. It is also to be understood that the terminology used in the description is for the purpose of describing the particular embodiments only, and is not intended to limit the scope of the present invention.

I CLAIM:
1. An herbal extract for treatment of renal calculi, comprising solvent extracts from Euphorbia hirta, wherein solvent extract comprises 2%-20% w/v of roots of Euphorbia hirta.
2. The herbal extract as claimed in claim 1, wherein the solvent can be selected from water, alcohol and a combination thereof.
3. The herbal extract as claimed in claim 1, wherein the solvent is an alcohol selected from the group consisting of methanol, ethanol, iso-propanol, and butanol.
4. The process of preparation of an herbal formulation comprising the steps of:
i. washing, drying and grinding of roots of Euphorbia hirta to get powdered form of herb;
ii. taking the powdered herb from step (i) in a solvent in a ratio of 1:20 (w/v) to get a solution; iii. extraction of the solution obtained in step (ii) at a temperature of 25°C- 45°C to get an extract;
iv. concentrating the extract obtained from step (III), followed by drying of extracts at 50°C- 60°C using rotary evaporator to get dried powder of Euphorbia hirta; and
v. adding pharmaceutically acceptable excipients to the dried extract obtained from step (IV) to get an herbal formulation.
5. The process of preparation of an herbal formulation as claimed in claim 4, wherein the solvent is selected from water, alcohol and a combination thereof.

6. The process of preparation of an herbal formulation as claimed in claim 4, wherein the solvent is an alcohol selected from the group consisting of methanol, ethanol, iso-propanol, and butanol.
7. A process of preparation of an herbal formulation as claimed in claim 4, wherein at least one pharmaceutically acceptable excipient is selected from the group consisting of a buffering agent, a preservative, a bulking agent, a binder, a disintegrant, a suspending agent, encapsulating materials, chelating agent, a glidant, a flavouring agent, a colouring agent, a tonicity agent, a co-solvent, and a combination thereof.