Field of Invention
This invention relates to a process of preparing a formulation for the treatment of Varicose veins and Hemorrhoids. At present there is no specific and proven treatment of Varicose veins and Hemorrhoids.
Prior Art
General practitioners encounter a large number of patients suffering from the manifestations of decreased vascular integrity, two of the most common being Varicose veins and Hemorrhoids. Conservative therapies such as diet, hydrotherapy, mechanical compression for Varicose veins, topical agents for Hemorrhoids, and lifestyle factors are the standard non invasive approaches to these conditions.
As with all disease, the primary treatment for Varicose veins and Hemorrhoids is prevention. Patients with risk factors for developing these conditions should be identified through history and physical exam before aggressive intervention is necessary. The use of diet, lifestyle, and hydrotherapy in addition to bioflavonoids such as Proanthocyanidin can intervene in the pathogenesis of decreased vascular integrity. Early intervention with these non-invasive therapies may prevent time consuming and expensive complications of both Varicose veins and Hemorrhoids.
The next line of therapy involves the use of semi-invasive non surgical modalities including electro coagulation, sclerotherapy, cryotherapy, photocoagulation and diathermy. These modalities require specific training, specialized equipment and are associated with some risk.
• Currently, for the treatment of Varicose veins and Hemorrhoids the available treatment is at best palliative and does not give complete relief
• Invasive surgical options are there, but patients prefer to avoid surgery as far as possible.
Available conservative therapy
• Diet
• Hydrotherapy
• Mechanical compression for Varicose veins
• Topical agents for Hemorrhoids
• Change in Life Style
Semi-invasive non surgical alternatives include
• Electro-coagulation
• Sclerotherapy
• Cryotherapy
• Photocoagulation
• Diathermy
These modalities require specific training, specialized equipment and are associated with some risk.

In one of the recent advancement in the knowledge of grape seeds extract (Proanthocyanidin), they are found to block the deterioration of blood vessels and have strengthening effect on their walls; therefore they help to keep damaged, stretched, or stiff blood vessels from leaking and improve the conditions involving veins and arteries.
Effect on Collagen Fibers
The Proanthocyanidin has a strong affinity for Collagen, the most abundant protein found in the human body. It is the key ingredient found in blood vessels as well as cartilage, tendons, skin and muscle, which act as glue in the body. The ultimate role may be to strengthen blood vessels, thereby by reducing leakage of fluid and blood. An important property of Proanthocyanidin, shown in certain studies, is that they are able to attach onto collagen and create cross links. Therefore, Proanthocyanidin tend to stabilize collagen fibers, because stability of collagen depends mainly upon the cross links which exist between the building blocks a helical polypeptide chains.
Effects on histamine and other mediators of inflammation
Oligometric Proanthocyanidin also gives protection against inflammation and alleviation of the symptoms of inflammation. Proanthocyanidin appear to inhibit the chemical mediators of the inflammatory response in a similar fashion as the NSAID's, thus, through the inhibition of the enzymes responsible for the synthesis of prostaglandin. They decrease tissue inflammation as a result of their inhibition of the enzymes lipoxygenase and cyclooxygenase thus preventing the synthesis of the body's chemical pain and inflammatory mediator's prostaglandins, kinins, histamine, leukotrines, and serotonin. Additionally, they decrease allergic reactivity by inhibiting mast cell and basophile degranulation and inhibition of histidine decarboxylase thereby depleting histamine.
Therapeutic usefulness of Proanthocyanidin
The best documented use of Proanthocyanidin is to treat Varicose veins and conditions closely related to it (Chronic Venous insufficiency). In these conditions, blood pools in the legs, causing aching, pain, heaviness, swelling, fatigue, and unsightly visible veins.
Proanthocyanidin provide relief in Varicose veins in the following manner
Strengthening of blood vessels
Proanthocyanidin has unique ability to strengthen the walls of blood vessels, weakened by age and disease. Proanthocyanidin thus reverses the fragility of blood vessels, making them more intact and supple so blood flows through easily and does not leak out as seen in Varicose veins. Proanthocyanidin accomplishes this by actually reacting tougher, thicker, more tightly knit blood vessel walls that are less likely to stretch, leak, or burst.

Proanthocyanidin protect the blood vessels, in four separate pathways
The Proanthocyanidin crosslink with collagen fibers in the basement membranes of vessel wall and make them stronger and less permeable.
Proanthocyanidin also attached to elastin, preventing their degradation by destructive enzymes and encouraging their synthesis and maturation.
The anti-oxidant action prevents degeneration and weakening of vessel wall due to aging. As an effective antioxidant, Proanthocyanidin help our body resist blood vessel damage, inflammation and other damages caused by harmful free radicals. However, their function is more than protection. They help repair by improving and stabilizing the collagen and improving the conditions of arteries and capillaries.
The Proanthocyanidin inhibit the production of histamine which prevents the histamine associated increase in permeability. In addition, Proanthocyanidin allow adrenalin to function for an extended time period by blocking the COMT enzyme, thereby allowing for increase vessel resistance to enzyme degradation.
Thus, Proanthocyanidin prevents degradation by elastases and coUagenases, which occur in inflammatory processes.
By protecting and carrying vitamin C to the basement membrane. Vitamin C is enabled to function more effectively in the production of the collagen needed to keep the vessels strong.
Formulation is characterized by the following ingredients in the proportion as indicated
Each film coated tablet contains
Proanthocyanidin 100 mg
(Derived from grape seed extract)
Vitamin C 50 mg
Mode of Action
Proanthocyanidin has phlebotonic, vasculoprotective and antagonistic action against inflammatory mediators. It helps to keep damaged, stretched or stiff blood vessels from leaking and improve conditions involving veins and arteries.
Proanthocyanidin has a strong affinity for collagen, the key ingredient found in blood vessels as well as cartilage, tendons, skin and muscle. Collagen acts as glue in the body. An important property of collagen is that they are able to attach on collagen and create cross links. Therefore, Proanthocyanidin tend to stabilize collagen fibers, because stability of collagen depends mainly upon the cross links which exist between the building blocks a helical polypeptide chains.

Proanthocyanidin also potentiates the Vitamin (J, indirectly strengtnenmg tne collagen fibrils, because Vitamin C is needed as enzyme in the formation of collagen.
Effects on collagenases and Elastases :
• The Proanthocyanidin avidly binds to elastin fibers.
• Affects the rate of degradation of elastin fibers by elastase making it resistance to the hydrolysis.

•
•

This novel Grape seed extracts having (+)- catechin binds tightly to collagen or elastin thus modifying its structure sufficiently. Thus making it resistant to enzyme degradation.
Thus, Proanthocyanidin prevents degradation by elastases and coUagenases, which occur in inflammatory processes.

Example
Clinical Trial Report -1
In an open prospective study, patients suffering from venous - lymphatic insufficiency were treated with Proanthocyanidin for three months {the daily dose was 2x150 mg.} The efficacy of the treatment was evaluated by statistical methods analyzing the changes of the clinical symptoms and the satisfaction of the dermal microcirculation before and after 3 months of treatment. Subjective complaints of the patients such as pain, heaviness of the leg, nightly muscle cramps were estimated by a visual analog scale. The treatment significantly reduced lymph edema (p<0.1) in the "heavy leg" syndrome. Symptoms as pain, heaviness of the leg, muscle cramps, improved significantly (p<0.001) after treatment.
Clinical Trial Report - II
A 2 months, double - blind, placebo - controlled trial of 40 people with chronic venous insufficiency found that 100 mg of Proanthocyanidin - three times daily significantly reduced edema, pain, and the sensation of leg heaviness. A similar study of 20 individuals also found Proanthocyanidin from pine bark effective.
Clinical Trial Report - III
A placebo - controlled study that enrolled 364 people with Varicose veins found that treatment with grape seed Proanthocyanidin produced statistically significant improvements as compared to baseline. There was a lesser response in the placebo group.

Clinical Trial Report - IV
A randomized placebo - controlled double blind study with 20 patients diagnosed with venous insufficiency and hepatic cirrhosis showed significant improvements in the capillary fragility index, compared to placebo, in patients receiving 2 x 150mg. Proanthocyanidin daily for 8 weeks.
Clinical Trial Report - V
An assessment of the relative effects of daily 150 mg Proanthocyanidin, and placebo over a 30 day period was done. The Proanthocyanidin - treated group experienced significantly fewer indications of functional problems, suggesting a potential treatment therapy for Varicose veins.
Clinical Trial Report - VI
In another double - blind study comparing Proanthocyanidin and placebo in 50 female patients, aged 20-60, similar treatments were administered to two groups of subjects, most with pregnancy - related chronic venous insufficiency, over 30 days. The Proanthocyanidin were effective in reducing symptoms of peripheral venous insufficiency, in terms of rapidity of action and duration of activity. Also, a significant decrease in Varicose veins, compared to baseline, was observed only in the Proanthocyanidin group.
Clinical Trial Report - VH
A 2 months, double - blind, placebo-controlled trial of 120 individuals with recurrent hemorrhoid flare - ups found that treatment with Proanthocyanidin significantly reduced the frequency and severity of hemorrhoid attacks.
Clinical Trial Report - VIII
Another double blind, placebo-controlled trial of 100 individuals had positive results with the same bioflavonoids Proanthocyanidin in relieving symptoms once a flare - up of hemorrhoid pain had begun.
Clinical Trial Report - IX
A 90 day, double blind trial of 100 individuals with bleeding Hemorrhoids also found significant benefits for both treatment of acute attacks and prevention of new ones.

Clinical Trial Report - X
A clinical study proved that Proanthocyanidin results to comparable with that of
surgical treatment of Hemorrhoids.
Claims
Considering the above mentioned actions, acting in synergism, Proanthocyanidin is useful in variety of conditions. Proanthocyanidin is considered as potent antioxidant that has been strongly associated with virtually every chronic disease including cardiovascular disease, arthritis, etc. In addition to their free radical scavenging activity they have been reported to have antibacterial, antiviral, ant carcinogenic, antiinflammatory, anti-allergic, and vasodilator actions. They are thought to help heart tissue in recovery after the ischemia, and can slow or reverse the atherosclerosis might be helpful or preventing heart disease.
Clinical Prospects
Free radical damage has been strongly associated with virtually every chronic degenerative disease, including cardiovascular disease, arthritis, and cancer. Free radicals are highly reactive and cause tissue damage by reacting with polyunsaturated fatty acids found in cellular membranes, nucleotides in DNA, and sulfhydryl bonds in proteins. Free radicals may originate endogenously from polluted air, solvent-laden water, pesticide-laced food, or radiation exposure.
Clearly, due to their antioxidant activity, the therapeutic potential of Proanthocyanidin is quite broad. The main stay of its clinical use is in the treatment of vascular disorders such as venous insufficiency. Varicose veins, Hemorrhoids and micro vascular problems including capillary fragility and retinopathies.
Royer and Schmidt observed improved venous tone from a single dose of 150mg Proanthocyanidin, as measured by gas plethysmography, in patients with widespread Varicose veins.
The costly and uncomfortable nature of treatment options often leads a patient to postpone evaluation until aggressive intervention is necessary. Oral dietary supplementation is an attractive addition to the traditional treatment of Hemorrhoids and Varicose veins. The loss of vascular integrity is associated with the pathogenesis of both Hemorrhoids and Varicose veins. Several botanical extracts such as Proanthocyanidin have been shown to improve micro circulation, capillary flow, and vascular tone, and to strengthen the connective tissue of the perivascular amorphous substrate.
Every general practitioner sees a large number of patients who suffer from problems associated with venous insufficiency. Two of the most common manifestations of venous insufficiency are Varicose veins and Hemorrhoids. The prevalence of these

two conditions is astonishing. In population studies the prevalence of Varicose veins has been reported to be 10-15 percent for men and 20-25 percent for women. In a recent cross-sectional study, the age-adjusted prevalence of Varicose veins was 58 percent for men and 48 percent for women.
Chronic venous insufficiency of the lower limbs has varied expressions : purely functional disorders, Varicose veins, varicosities, oedema and tropic cutaneous disorders. For a given individual, these aspects are not necessarily increasing stages of severity of the same disease. On the other hand, many associations are possible; they are determined by the mechanism and the degree of chronic venous insufficiency, as well as by the clinical situation in which they develop. Venous diseases become steadily more common and severe with age, and are often accompanies by venous lymphatic oedema.
Effects on Histamine and other mediators of inflammation

•
Proanthocyanidin inhibit the chemical mediators of inflammatory response (in similar fashion as the NSAID's)
• Proanthocyanidin inhibits enzymes lipooxygenase and cyclooxygenase. Thus prevents synthesis of pain and inflammatory mediators, prostaglandins, kinins, histamine, leukotrienes, and serotonin.
• Prostaglandin also decreases allergic reactivity by inhibiting degranulation of mast cells and basophils and thus inhibits histidine decarboxylase. This result in depletion of histamine.
Therapeutic usefulness of Proanthocyanidin
• The best documented use of Proanthocyanidin is to treat Varicose veins and condition closely related to chronic venous insufficiency.
• Proanthocyanidin provides relief from conditions such as pooling of blood in the legs, which causes aching, pain, heaviness, swelling, fatigue and unsightly visible veins.
Proanthocyanidin - Strengthening of blood vessels
• Proanthocyanidin has unique ability to strengthen the walls of blood vessels, weakened by age and disease.
• Proanthocyanidin reverses the fragility of blood vessels, making them more intact and supple, so blood flows through easily and does not leak out as seen in Varicose veins.
• Proanthocyanidin accomplishes this by actually creating tougher, thicker, more tightly knit blood vessel walls that are less likely to stretch, leak, or burst.

Proanthocyanidin protects the blood vessels in four separate pathways
• The Proanthocyanidin crosslink with collagen fibers in the basement membranes
of vessel walls, which makes them stronger and less permeable.
Proanthocyanidin also get attached to elastin, preventing their degradation by destructive enzymes and encouraging their synthesis and maturation.
Proanthocyanidin with their antioxidant action help repair by improving and stabilizing the collagen and improving the conditions of arteries and capillaries.
• Proanthocyanidin by protecting and carrying vitamin c to the basement membrane,
enables vitamin c to function more effectively in the production of the collagen
needed to keep the vessels strong.

•
Proanthocyanidin inhibit the production of histamine which prevents the histamine associated increase in permeability and itching.
• Proanthocyanidin allow adrenalin to function for an extended time period by blocking the COMT enzyme, thereby allowing for increased vessel resistance.
It is to be noted that the prior art description give in detail information of the technology, method, process and system known in the art. It explain the deficiency in the related art and the object of the invention being to overcome or surmoimt the problem associated with the prior art. This forms the essential feature and the object of the invention.
SUMMARY OF INVENTION
The inventors have made great effort to provide a system which meet the requirement of the industry and overcome the problem associated in the prior art.
To achieve the above object according to first aspect and feature of the present invention there is provided a system to improve, efficiency.
According to second aspect and feature of the invention in addition to the first feature the invention comprises a system, which is unique, rugged efficient, economical.
At the outset of the description which follows it is to be understood that ensuring description only illustrates a particular from of this invention. However, such particular form is only an exemplary embodiment without intending to imply any limitation on the scope of this invention. Accordingly, the description is to be understood as an exemplary embodiment and reading of the invention is not intended to be taken restrictively.

The above and other objects features and disadvantages will be clear from the following description of preferred embodiment taken in conjunction with accompanying drawings.
The foregoing description is outlined rather broadly preferred and altemative feature of the present invention so that those skilled in the art may better understand the detailed description of the invention that follows. Additional features of the invention will be described hereinafter that form the subject of claims of the invention. Those skilled in the art should appreciate that they can readily use the disclosed conception and specific embodiment as a basis for designing and modifying other structures for carrying out the same purposes of the present invention. Those skilled in the art should realize such equivalent conception do not depart from the spirit and scope of the invention in its broadest form.
BRIEF DESCRIPTION OF DRAWINGS
The accompanying drawings is intended to provide further understanding of invention and is incorporated in and constitute a part of invention. The drawings illustrate an embodiment of invention and together with the description illustrate principle of invention.
The drawings should not be taken as implying any necessary limitation on the essential scope of invention.
The drawings are given by way of non-limitative example to explain the nature of the invention.
For a more complete understanding of the instant invention reference is now made to the following description taken in conjunction with accompanying drawings.
• Figure 1 of the drawings shows the structure of Proanthocyanidin
• Figure 2 shows the regulation of resistance and Permeability
• Figure 3 shows the role of Vitamin C
• Figure 4 shows the various process details for manufacturing the formulation.
The various feature of novelty which characterise the invention are pointed out specifically in the claims which a part of description. For a better understanding of the invention, its operating advantage, specific objects obtained by its use, reference should be made to the drawings and descriptive matter in which they are illustrated and described preferred embodiments of invention.
Referring now to drawings, where like numerals designate identical or corresponding parts throughout the referred views.

Description
• Each film coated tablet contains
• Proanthocyanidin 100 mg(Derived from Grape seed extract) Vitamin C 50 mg
Working example of invention
•
The active ingredient powders are taken 38% to 40% by weight of the total formulation while the other constituents are 62% to 60% by weight of the total formulation, more preferably.
• Active ingredients 38% to 40%
• Binders 5% to 6%
• Diluents 42% to 45%
• Lubricants 4% to 5%
• Coating Materials 5% to 6% of the total formulation
Explicit statement of the invention
According to this invention, it provides a formulation derived from grape seeds extract for the treatment of Varicose veins and Hemorrhoids, comprising the following steps.
• Selecting the active ingredient from the grape seed extract.
• Pulverizing the said seed extracts into coarse powder.
• Mixing the grape seed extract containing Proanthocyanidin as active ingredient and Vitamin C with the lubricants, then making into wet mass with the help of binders and then reducing into desired size granules and drying and making into tablets with the help of lubricants.
• The core tablets then film-coated with the coating materials.
Proanthocyanidin
• Proanthocyanidin has also the following actions
• Antibacterial, antiviral, anti carcinogenic, anti inflammatory, anti allergic and vasodilation.
• Slows or reverses the atherosclerosis.
Proteins in the vessel wall, collagen and elastin, greatly determine the elasticity and permeability of the vascular wall, whether the wall is solid, strong, and flexible, or fragile and leaky.
Proanthocyanidin reinforces the structure of the connective tissue that makes blood vessels strong and resistant.
Proanthocyanidin along with Vitamin C is a multifunctional medicine having applications in variety of medical conditions.

BIOAVAILABILITY & SAFETY PROFILE
• The bioavailability and safety profile of the Proanthocyanidin is very encouraging,
and so far no adverse event has been documented with the use of
Proanthocyanidin.
Distinguishing features of the invention with prior art
• The main object of this invention is to provide complete relief for patients of Varicose veins, Hemorrhoids and venous insufficiency with out invasive surgical procedure.
• This invention relates to the non invasive therapeutic alternative for treating Varicose veins, Hemorrhoids and venous insufficiency and provide relief from discomfort.
Distinguishing features of the invention with prior art

•
General practitioners see many cases of Varicose veins. Hemorrhoids and venous insufficiency and are looking for a non invasive alternate therapy.
•
Early intervention with this non invasive therapy will prevent time consuming and expensive complications of Varicose veins and Hemorrhoids.
The invention is an efficacious preparation that sets right the root cause of these problems.
The invention has been explained in relation to specific embodiment. It is inferred that the foregoing description is only illustrative of the present invention and it is not intended that the invention be limited or restrictive thereto. Many other specific embodiments of the present invention will be apparent to one skilled in the art from the foregoing disclosure. All substitution, alterations and modification of the present invention which come within the scope of the following claims are to which the present invention is readily susceptible without departing from the spirit of the invention.
The scope of the invention should therefore be determined not with reference to the above description but should be determined with reference to appended claims along with full scope of equivalents to which such claims are entitled.

WE CLAIM
1 A formulation for the treatment of Varicose veins and Hemorrhoids compresses the following ingredients and their proportion for each tablet.
Ingredients Proportion
a) Grapes seed extract and Vitamin C 38% to 40%
b) Binders 5% to 6%
c) Diluents 42% to 45%
d) Lubricants 4% to 5%
e) Coating Materials 5% to 6% of the total formulation
Each film coated tablet contains
Proanthocyanidin (Derived from Grape seed extract) 100 mg
Vitamin C 50 mg
2. A formulation for the treatment of Varicose veins and Hemorrhoids compresses the following ingredients and their proportion for each tablet as claimed in Claim 1 wherein the active ingredient powders are taken 38% to 40% by weight of the total formulation while the other constituents are 62% to 60% by weight of the total formulation, more preferably.
3. A formulation as claimed in Claim 1 wherein each film coated tablet contains Proanthocyanidin (Derived from Grape seed extract) 100 mg
Vitamin C 50 mg
4. A method of formulation derived from grape seeds extract for the treatment of
Varicose veins and Hemorrhoids, comprising the following steps.
a) Selecting the active ingredient from the grape seed extract.
b) Pulverizing the said seed extracts into coarse powder.
c) Mixing the grape seed extract containing Proanthocyanidin as active ingredient and Vitamin C with the lubricants, then making into wet mass with the help of

binders and then reducing into desired size granules and drying and making into tablets with the help of lubricants.
d) The core tablets then film-coated with the coating materials.
5. A formulation for the treatment of Varicose veins and Hemorrhoids compresses the following ingredients and their proportion for each tablet as described in the complete specification
• Active ingredients 38% to 40%
• Binders 5% to 6%
• Diluents 42% to 45%
• Lubricants 4% to 5%
• Coating Materials 5% to 6% of the total formulation
6. A method of formulation for the treatment of Varicose veins and Hemorrhoids compresses the following ingredients and their proportion for each tablet.