FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
[See section 10 and rule 13]

TITLE OF THE INVENTION FOOD SUPPLEMENT COMPOSITION FOR ORAL USE IN THE TREATMENT OR PREVENTION OF URINARY TRACT INFECTIONS
2. APPLICANT
Name Nationality Address
Fullife Healthcare Pvt Ltd. India 418, Samartha Aishwarya, Lokhandwala Complex, Andheri (West), Mumbai - 400053, India, Mumbai, Maharashtra, 400053

The following specification particularly describes and ascertains the nature of the invention and
the manner in which it is to be performed.

FOOD SUPPLEMENT COMPOSITION FOR ORAL USE IN THE TREATMENT OR PREVENTION OF URINARY TRACT INFECTIONS
FIELD OF THE INVENTION
[01] The present invention generally relates to a food supplement composition
for oral use in the treatment or prevention of urinary tract infections. The invention also relates to various dosage forms of the said composition and to a method of preparing the said composition.
BACKGROUND OF THE INVENTION
[02] Urinary tract infection (UTI) is the most common infection affecting
primarily women all over the world. Incidence of UTI is higher in women than men, 40% to 50% of whom will suffer at least one clinical episode during their lifetime. UTIs account for over 11.3 million office visits and 1.5 million emergency department visits per year. These statistics become even more staggering when combined with the fact that fewer than 40% of women seek clinical care for what they believe are UTIs. Approximately 13.3% of women suffer from UTIs each year. The increased risk factor for UTI in women may be due to short urethra, absence of prostatic secretions, menopause, incontinence with age, pregnancy and easy contamination of urinary tract with fecal flora.
[03] The cause of urinary tract infections is well-documented with over 85% of
infections due to Escherichia coli (E. coli) bacteria. E. coli normally live in the colon and do not cause infections when they remain in the colon. The urinary tract and urine

are normally sterile. There are a number of ways that E. coli can find their way to the urinary tract, most commonly through sexual intercourse, poor hygiene, or catheters.
[04] E. coli are oblong bacteria with finger-like appendages called fimbriae that
allow them to be mobile. A small amount of E .coli can invade the urethra, and then make their way into the bladder. The bacteria then multiply very rapidly and begin to release toxins that cause the bladder to spasm. When the bladder begins to spasm, the patient feels pain, urgency, and urinates multiple times an hour.
[05] Common symptoms of a UTI include urinary frequency and pain. While
uncomplicated UTIs in women are usually benign in nature, a UTI elevates the risk of premature delivery and fetal mortality among pregnant women. Furthermore, a simple UTI can progress to pyelonephritis (kidney infection), bacteremia (bacteria in the blood), sepsis (whole body infection), or death. In elderly patients, UTIs are a significant cause of mortality; up to 3% of elderly patients who develop pyelonephritis die from their UTI. This leads to increase in demand of products that are used for treatment or prevention of UTI.
[06] Cranberries contain A-type proanthocyanidins (PACs)—the active ingredient
for UTI prevention. Proanthocyanidins prevent the adherence of E. coli fimbriae to the urinary tract wall, thereby blocking E. coli from sticking to the bladder wall.
[07] Cranberry products have gained popularity for prevention of UTI owing to
their natural origin. Diet cranberry juice products available commercially are heavily diluted (5-7% juice) and are also laden with artificial ingredients and sweeteners. Cranberry juice cocktail (typically 27% juice) represents one of the most caloric drinks available, with 137 calories per 8 fl. Oz. The high levels of sugar and calories in cranberry juice cocktails prove especially problematic for UTI sufferers who also

suffer from diabetes or gestational diabetes. Similarly, the low pH of cranberry juice
cocktails could be problematic for patients also suffering from gastrointestinal
problems, such as ulcers.
[08] Cranberry pills have failed to capture consumer loyalty because they contain
scant active ingredients. Cranberry pills also suffer from low consumer awareness.
Furthermore, cranberry pills fail to promote hydration and flushing; hydration is
critical during an acute infection and for prevention.
[09] Cranberry products generally contain cranberry extract in combination with
other substances. These ingredients reduce the recurrence of infection but may or may
not help in reducing certain unbearable symptoms of UTI.
[10] There is a need for a product that alleviates painful symptoms of UTI while
also preventing worsening of the infection.
SUMMARY OF THE INVENTION
[11] According to an embodiment of the invention there is provided a food
supplement composition for oral use in the treatment or prevention of urinary tract infections comprising 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 3 to 9 % by weight D-Mannose, and 75 to 95 % by weight excipients in an effervescent form of the composition. The non-effervescent granule form of the composition comprises 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 65 to 75 % by weight D-Mannose and 25 to 35 % by weight excipients.

[12] According to another embodiment of the invention there is provided a
method of preparing a food supplement composition for oral use in the treatment or prevention of urinary tract infections comprising mixing 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 3 to 9 % by weight D-Mannose, and 75 to 95 % by weight excipients in an effervescent form of the composition. The non-effervescent granule form of the composition comprises 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 65 to 75 % by weight D-Mannose and 25 to 35 % by weight excipients.
[13] According to yet another embodiment of the invention there are provided
dosage forms comprising the composition of the invention in combination with suitable excipients, wherein the dosage forms are tablets, granules, capsules, effervescent granules, effervescent granules with an alkalizing agent, effervescent tablets, non-effervescent granules.
BRIEF DESCRIPTION OF THE DRAWINGS
[14] Fig. 1 is a graphical representation of the increase in the time interval
between two successive recurrences for patients who received the effervescent
granule form of the composition of the invention.
[15] Fig. 2 is a pie-chart representation of the reduction in pain and burning in
patients who received the effervescent granule form of the composition of the
invention.

[16] Fig. 3 is a graphical representation of the efficacy of the effervescent
granule form of the composition of the invention in comparison to other
cranberry products.
[17] Fig. 4 is a graphical representation of the patients’ preference of
effervescent granule form of the composition of the invention form over other
dosage forms.
[18] Fig. 5 is a graphical representation of the cost effectiveness of the
effervescent granule form of the composition of the invention as compared to
antibiotic therapy.
DETAILED DESCRIPTION OF THE INVENTION
[19] In the following detailed description, reference is made to the
accompanying drawings that form a part hereof. The embodiments of the invention are described in sufficient detail to enable those skilled in the art to practice the invention and it is understood that other embodiments may be utilized and that logical processual changes may be made without deviating from the spirit or scope of the invention. To avoid details not necessary to enable those skilled in the art to practice the embodiments described herein, the description may omit certain information known to those skilled in the art. The following detailed description is, therefore, not to be taken in a limiting sense and the scope of the illustrative embodiments are defined only by the appended claims.
[20] The present invention relates to a food supplement composition for oral
use in the treatment or prevention of urinary tract infections comprising 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium

macrocarpon extract, 3 to 9 % by weight D-Mannose, and 75 to 95 % by weight excipients in an effervescent form of the composition. The non-effervescent granule form of the composition comprises 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 65 to 75 % by weight D-Mannose and 25 to 35 % by weight excipients.
[21] The method of the invention involves preparing a food supplement
composition for oral use in the treatment or prevention of urinary tract infections comprising by mixing 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 3 to 9 % by weight D-Mannose, and 75 to 95 % by weight excipients in an effervescent form of the composition. The non-effervescent granule form of the composition comprises 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 65 to 75 % by weight D-Mannose and 25 to 35 % by weight excipients.
[22] The excipients can comprise natural colors, flavors, binders, acidity
regulators, effervescent agents, antifoaming agents, lubricants or combinations thereof. The Salvia officinalis extract preferably comprises ursolic acid while the Vaccinium macrocarpon extract preferably comprises proanthocyanidins. Preferably, the effervescent agent is a combination of citric acid anhydrous and sodium bicarbonate.
[23] The invention also provides a variety of dosage forms comprising the
composition of the invention in combination with suitable excipients, wherein the dosage forms are tablets, granules, capsules, effervescent granules,

effervescent granules with an alkalizing agent, effervescent tablets. Preferably, the alkalizing agent is potassium magnesium citrate.
[24] The invention also provides a compressed solid unit dosage form for oral
use in the treatment or prevention of urinary tract infections, comprising the composition of the invention in combination with a binding agent and pharmaceutically acceptable excipients. Preferably, the binding agent is maltodextrin.
[25] The invention also provides soluble granules for oral use in the treatment
or prevention of urinary tract infections, comprising the composition of the invention in combination with pharmaceutically acceptable excipients.
[26] The invention also provides effervescent granules for oral use in the
treatment or prevention of urinary tract infections comprising the composition of the invention in combination with effervescent agents and pharmaceutically acceptable excipients.
[27] The composition of the invention comprises Salvia officinalis extract
derived from the aerial parts of the Sage leaf (Salvia officinalis L), with a high content of ursolic acid. Ursolic acid is an excellent anti-inflammatory agent.
[28] The composition of the invention also comprises a proprietary cranberry
(Vaccinium macrocarpon) extract which has substantially high A-type Proanthocynadins (PACs) content. A-type PACs are the active phytochemicals which prevent infection-causing bacteria from attaching to the urinary tract walls.

[29] The composition of the invention is the only product available
commercially at present which contains cranberry extract with 50 % Proanthocynadins. It is effective against infections caused by E. coli p-fimbriae, Klebsiella, Pseudomonas and Staphylococcus. Ursolic acid and its metabolites are the main compounds responsible for reduction of inflammatory symptoms in urinary tract infections caused by E. coli p-fimbriae. D-Mannose is a naturally occurring simple sugar closely related to glucose, which sticks to E. coli and acts as a decoy agent. D-Mannose works by promoting the activation of Tamm-Horsfall protein. D-Mannose has the ability to behave as a multivalent ligand and significantly enhances the protective role of the composition in UTIs. Salvia officinalis extract, Cranberry extract and D-Mannose, together make a perfect combination and synergistically complement each other’s functionalities for preventing urinary tract infections and inflammation.
[30] The following experimental examples are illustrative of the invention but
not limitative of the scope thereof:
Example 1: Preparation of effervescent granules of the composition
[31] About 100 mg Salvia officinalis extract was mixed with about 140 mg D-
Mannose, 10 mg acesulfame potassium as a sweetening agent along with 500 ± 100mg sodium carbonate anhydrous. The mixture was dried and then sprayed with a solution of maltodextrin in water as a binding agent and then semi-dried. To this semi-dried mixture were added and mixed about 70 ± 10 mg cranberry extract, 900 ± 100 mg citric acid anhydrous, and 100 ± 50 mg beetroot powder for colour. The mixture was again dried and then sprayed with solution of

maltodextrin in water as a binding agent and then semi-dried and granulated. Lastly, flavor and sweetening agents were blended into the composition.
Example 2: Preparation of effervescent tablet form of the composition
[32] About 100 mg Salvia officinalis extract was mixed with about 140 mg D-
Mannose, 10 mg acesulfame potassium as a sweetening agent, along with 65mg sodium carbonate anhydrous and 300 mg sodium bicarbonate. The mixture was dried and then sprayed with a solution of maltodextrin in water as a binding agent and then semi-dried. To this semi-dried mixture were added and mixed about 70 ± 10 mg cranberry extract, 900 ± 100 mg citric acid anhydrous, 15 ± 5 mg silicon emulsion and 100 ± 50 mg beetroot powder for colour. The mixture was again dried and then sprayed with solution of maltodextrin in water as a binding agent and then semi-dried and granulated. Lastly, strawberry flavour, and sucralose were blended into the composition.
Example 3: Preparation of effervescent granule form of the composition comprising an alkalizing agent
[33] About 100 mg Salvia officinalis extract was mixed with about 140 mg D-
Mannose, 20 mg acesulfame potassium as a sweetening agent, along with 500 ± 100 mg sodium carbonate anhydrous. The mixture was dried and then sprayed with a solution of maltodextrin in water as a binding agent and then semi-dried. To this semi-dried mixture were added and mixed about 70 ± 10 mg cranberry extract, 900 ± 100 mg citric acid anhydrous, potassium magnesium citrate comprising 240mg potassium and 35 mg magnesium, and 100 ± 50 mg beetroot

powder for colour. The mixture was again dried and then sprayed with solution of maltodextrin in water as a binding agent and then semi-dried and granulated. Lastly, raspberry flavour and sweetener was blended into the composition.
Example 4: Preparation of non-effervescent granules of the composition
[34] About 100 mg Salvia officinalis extract was mixed with about 2500 mg
D-Mannose, 20 mg acesulfame potassium as a sweetening agent. The mixture was dried and then sprayed with a solution of maltodextrin in water as a binding agent and then semi-dried. To this semi-dried mixture were added and mixed about 70 ± 10 mg cranberry extract and 100 ± 50 mg beetroot powder for colour. The mixture was again dried and then sprayed with solution of maltodextrin in water as a binding agent and then semi-dried and granulated. Lastly, Strawberry flavour and sweetener was blended into the composition.
Example 5: Field study
[35] Market research methodology: Studies were carried out using the
quantitative research method to assess the efficacy of the composition of the invention. Gynecologists across India were a part of the study. A total of 34 doctors treating approximately 335 patients were interviewed for gathering medical intelligence on certain aspects of the composition of the invention. By elaborating upon the responses, the data has been quantified by classifying them into various categories and statistically portraying them into overall percentages.
[36] (1) Duration of treatment: When doctors were asked about duration for
which they prescribe the composition of the invention to patients, they responded

that the duration is dependent on the severity of infections that patients suffer from. Majority of the doctors feel that the effervescent granule form of the composition of the invention should be taken for 30 days for better results and for ensuring prevention of the infection.
[37] (2) Patients reporting positive experiences: When doctors were asked
about patients having positive experiences with the composition of the invention, they reported that 82 % ± 2.3 % patients were found to have positive experience. This data indicates the overall positive impact the composition of the invention has in reducing the recurrence of UTI as well as relieving the symptoms of UTI.
[38] (3) Increase in the time interval between two successive infections: In
patients with UTI recurrences, the infection used to occur at very short intervals (2-3 times a month). After using the composition of the invention, 25 % doctors have reported a recurrence interval of 1-3 months, 28% of doctors have reported a recurrence interval of 3-6 months and 47% of doctors have reported a recurrence interval of up to six months and/or more than six months (as shown in Fig. 1).
[39] (4) Anti-inflammatory potential of the composition on symptoms of
UTI: When doctors were asked about the reduction in pain and burning sensation in patients using the composition, 97% reported that there was a marked reduction in pain and burning sensation among patients who were prescribed the composition (as shown in Fig. 2)
[40] (5) Efficacy of the composition in Preventing Recurrence of UTI
compared to other Cranberry Products: The composition of the invention was

reported to have better efficacy than other cranberry products by majority of the doctors (as shown in Fig. 3). This may be due to the clinically effective concentration of Type-A PACs (50 percent by weight) in the Cranberry extract as well as the Ursolic acid present in the composition of the invention which synergistically exerts an anti-inflammatory action and decreases the severe symptoms in patients. Hence, patients experienced better relief.
[41] (6) Patient compliance with respect to the Dosage form: Doctors
claimed that 88% of patients preferred effervescent products over capsules and powders. Hence, the effervescent granule form of the composition of the invention has an advantage of increased patient compliance over other products (as shown in Fig. 4).
[42] (7) Cost effectiveness: 79% of doctors reported that the composition of
the invention was found to be cost effective in comparison to Antibiotic therapy and 21% of doctors found it to be similar to Antibiotics (as shown in Fig. 5)
[43] (8) Additional Advantages: Antibiotic resistance has increased and,
largely due to this, certain antibiotics show negligible efficacy in treatment of UTI. When doctors were asked about the composition of the invention for reducing the problem of antibiotic resistance, 79% of them felt that the composition may help in decreasing the problem of bacterial resistance against antibiotics by preventing widespread overuse or misuse of antibiotics.
[44] It is clear that the composition of the invention has shown wide
acceptance amongst women with recurrent UTI and they have reported an increase in the interval between two successive infections. Furthermore, the

composition leads to marked reduction in pain and burning sensations, which is
a unique feature of the composition. Other cranberry products do not show
decrease in pain, discomfort and burning sensation. Effervescent dosage form is
another unique feature of the composition which increases the patient
compliance and hence the acceptance of the effervescent granule form of the
composition. Subsequently, the composition was found to be a cost-effective
therapy as compared to multi-antibiotic therapy. Therefore, the composition is
recommended as an adjuvant therapy for UTI prevention by majority of the
doctors. Since the composition is a completely natural product, it has no side
effects as is seen with antibiotics. Further, the composition comprises the
sweetening agent sucralose which does not get metabolized by the body. The
composition also protects from kidney injury by down-regulating inflammation.
[45] As compared to other dosage forms, the effervescent granule form of the
composition was found to have several advantages. For one, there was better patient compliance with the effervescent granule form as it is better tasting than other cranberry preparations due to the superior taste masking achieved by complementing with flavors and fragrances. Also, the effervescent granule form of the composition is pH stable and was easy to use i.e. self-mixing due to the effervescent reaction leads to rapid and complete dissolution of the effervescent granules into the solution. Also, the effervescent granule form of the composition is easy to swallow when the granules are added to water. Drinkable solutions are easier to swallow than conventional Cranberry + D-mannose capsules. Hence, this form is extremely well-suited to those with swallowing difficulties, such as

the elderly, infirm, young children or those with esophageal injuries thereby
significantly increasing treatment preference and regimen adherence. Further,
the use of effervescent granules tends to produce a more reliable efficacy
response, as the active ingredients in the effervescent granule form of the
composition are evenly distributed, preventing variability due to disintegration
and dissolution of other formulations. Also, the effervescent granule form of the
composition is gentle on the digestive tract and therefore affords greater
tolerability. Buffering also prevents gastric acids from interacting with the
ingredients themselves, which can be a major cause of stomach and esophageal
upsets. Increase in liquid intake due to dissolving the effervescent granules in
liquid increases hydration. Proper hydration is essential for flushing the urinary
bladder and for good health and wellbeing.
[46] The above examples are non-limiting. The invention is defined by the
claims that follow.

We claim:
1. An effervescent food supplement composition for oral use in the treatment or prevention of urinary tract infections comprising 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 3 to 9 % by weight D-Mannose, and 75 to 95 % by weight excipients.
2. The composition as claimed in claim 1, wherein the excipients comprise natural colors, flavors, binders, acidity regulators, effervescent agents, antifoaming agents, lubricants or combinations thereof.
3. The composition as claimed in claim 1, wherein the Salvia officinalis extract comprises ursolic acid.
4. The composition as claimed in claim 1, wherein the Vaccinium macrocarpon extract comprises proanthocyanidins.
5. A non-effervescent food supplement composition for oral use in the treatment or prevention of urinary tract infections comprising 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 65 to 75 % by weight D-Mannose and 25 to 35 % by weight excipients.
6. The composition as claimed in claim 5, wherein the excipients comprise natural colors, flavors, binders, acidity regulators, antifoaming agents, lubricants or combinations thereof.
7. The composition as claimed in claim 5, wherein the Salvia officinalis extract comprises ursolic acid.
8. The composition as claimed in claim 5, wherein the Vaccinium macrocarpon extract comprises proanthocyanidins.

9. Dosage forms comprising the composition as claimed in claim 1 in combination with suitable excipients, wherein the dosage forms are tablets, granules, capsules, effervescent granules, effervescent granules with an alkalizing agent, effervescent tablets.
10. The dosage forms as claimed in claim 9, wherein the alkalizing agent is potassium magnesium citrate.
11. A compressed solid unit dosage form for oral use in the treatment or prevention of urinary tract infections comprising the composition of claim 1 in combination with a binding agent and pharmaceutically acceptable excipients.
12. The compressed solid unit dosage form as claimed in claim 11, wherein the binding agent is maltodextrin.
13. Soluble granules for oral use in the treatment or prevention of urinary tract infections comprising the composition of claim 5 in combination with pharmaceutically acceptable excipients.
14. A method of preparing an effervescent food supplement composition for oral use in the treatment or prevention of urinary tract infections comprising mixing 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 3 to 9 % by weight D-Mannose, and 75 to 95 % by weight excipients.
15. The method as claimed in claim 14, wherein the Salvia officinalis extract comprises ursolic acid.
16. The method as claimed in claim 14, wherein the Vaccinium macrocarpon extract comprises proanthocyanidins.

17. A method of preparing a non-effervescent food supplement composition for oral use in the treatment or prevention of urinary tract infections comprising mixing 2 to 8 % by weight Salvia officinalis extract, 1.5 to 5 % by weight Vaccinium macrocarpon extract, 65 to 75 % by weight D-Mannose, and 25 to 35 % by weight excipients.
18. The method as claimed in claim 17, wherein the Salvia officinalis extract comprises ursolic acid.
19. The method as claimed in claim 17, wherein the Vaccinium macrocarpon extract comprises proanthocyanidins.