FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rule 13)

1. TITLE OF THE INVENTION

A PHARMACEUTICAL COMPOSITION COMPRISING OFLOXACIN AND CEFUROXIME

2. APPLICANT (S)
(a) NAME : Biochem Pharmaceutical Private Limited
(b) NATIONALITY : An Indian
(c) ADDRESS : Aidun Building,
John Crasto Lane,
Near Metro Theatre
Mumbai -400 002
India.
3. PREMABLE TO THE DESCRIPTION
? PROVISIONAL

The following specification describes the invention.

The present invention relates to a pharmaceutical composition for the treatment of respiratory tract infections (RTIs), ear-nose-throat infections (ENTIs) and skin and skin structure infections (SSTIs).
More particularly, the present invention relates to the composition comprises ofloxacin and cefuroxime or salts of thereof.
BACKGROUND OF THE INVENTION
Respiratory tract infections (RTIs), ear-nose-throat infections (ENTIs) and skin and skin structure infections (SSTIs) place a considerable strain on the health budget. However in 2002 respiratory tract infections (RTIs) were still the leading cause of deaths among all infectious diseases, and they accounted for 3.9 million deaths worldwide and 6.9% of all deaths that year (http://www.who.int/entity/whr/2004/en/report04_en.pdf. As read on 12th May, 2010).
RTIs are mainly classified as to lower respiratory tract infections (LRTIs) and upper respiratory tract infections (URTIs). The two most common LRTIs are bronchitis and pneumonia. Pneumonia is leading cause of death especially in children less than five years. LRTIs are due to primarily three pathogens: Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catarrhalis {Reynolds R et al. J Antimicrob Chemother 2003; 52: 931-943; Ozylimaz E et al. Jpn J Infect Dis 2005; 58:50-52; Liebowitz LD et al. J Clin Pathol 2003; 56: 344-347}. In addition to the three pathogens mentioned, others commonly include Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae {Jones RN. Diagn Microbiol Infect Dis 2002; 44(3): 213-220}.
URTIs involve infection of upper respiratory tract like nose, sinuses, pharynx, and larynx. It is the leading reason for people missing work and school. UTRIsinclude pharyngitis, rhinitis, sinusitis, nasopharyngitis, epigtottitis, laryngitis and tracheitis. URTIs are dominated by: Streptococcus pneumoniae, Streptococcus pyrogenes, Hemophilus influenzae and Moraxella catarrhalis {Korner JR et al. BMJ 1994; 308: 191-192}.
ENT infections are also commonly seen in the general population. It mainly includes otitis externa, otitis media and other infection related to ear, nose and throat wherein Streptococcus pneumoniae and Streptococcus pyogenes are causative pathogens.
SSTIs are among the most common infection in the hospital setting. SSTIs are treated according to whether they are uncomplicated (uSSTIs) or complicated (cSSTIs). Uncomplicated infections include folliculitis, impetigo, erysipelas, cellulitis, furuncles, carbuncles, and non-perirectal abscesses. Complicated infections involve deeper tissue as well as skin. uSSSIs are caused by Staphylococcus aureus and Streptococcus pyogenes.
Non-pharmacological treatments and complementary therapies are an option adjunct to treat RTIs and ENTIs. The main stay of non-pharmacological treatment for many years has been rest and increase fluid intake. Although it is common for doctor and other health professional to recommend extra fluid intake a Cochrane systematic review could find no evidence for or against increased fluid intake. Although the idea of replacing fluid lost through fever and breathing was sound, some observational studies reported harmful effects such as dilution of blood sodium concentration leading to headache, confusion or seizure.
It is important to use appropriate microbial selection of an antimicrobial based on the infecting organism and to ensure this therapy changes with the evolving nature of these infections and the emerging resistance to conventional therapies. With increase development of drug resistance, traditional empirical treatments are becoming less effective, hence it is important to base antimicrobial choice for isolated bacteria.
Pharmacological treatments are another mainstay to treat RTIs, ENTIs and SSTIs. Broad spectrum antibiotic such as amoxicillin, amoxicillin with clavulanic acid, penicillin, chloramphenicol and various cephalosporins, and various cephalosporins, etc. are commonly used in the treatment of RTIs. Antimicrobials used in ENTIs are similar but in SSTIs, new antibiotics such as linezolid and daptomycin are available.
Ofloxacin is a synthetic antimicrobial, belonging to group called fluoroquinolones. One of the weaknesses of earlier generation of fluoroquinolones, including ofloxacin, is comparatively poor activity against streptococci. It seems logical that ofloxacin’s spectrum needs strengthening to broad base its antibacterial coverage of RTIs, ENTIs and SSTIs.
WO 97/20849 discloses derivative of 7-aminocep-3-em-2-carboxylic acid with 6-fluoroquinolone derivatives. These compounds posses antiviral, antimycoplasm, antibacterial, growth promoting and probiotic activity.
US 5066800 disclose process and intermediates used therein for linking a cephalosporin compound to a quinolone. Compounds prepared can be used as agents to combat bacterial infections including urinary tract infection and respiratory infections in mammals including humans.
US 2007/0054844 discloses a method for treating otitis externa using a topical combination medication including one or more antifungal agent and one or more antibacterial agent who include among others, a cephalosporin compound and a fluoroquinolone compound.
Some observational studies reported unwanted and harmful effects, when non-pharmacological treatments and complementary therapies were used {Guppy MPB MS, Del Mar CB., Cochrane Database of Systematic Reviews 2005, Issue Art. No.:CD004419. DOI 10.1002/ 14651858. CD004419. pub2.}. Because of continuously increase in drug resistance; it is a need to use appropriate antimicrobial choice. The techniques mentioned in the above stated inventions are laborious and lengthy.

OBJECT OF INVENTION
The main object of the present invention is to provide treatment for respiratory tract infections (RTIs), ear-nose-throat infections (ENTIs) and skin and skin structure infections (SSTIs).
Further object of the invention is to provide pharmaceutical composition comprising ofloxacin and cefuroxime or salts of thereof.
Another object of the invention is to make up for the weakness in the antimicrobial spectrum of ofloxacin.
Yet an object of the present invention is to overcome the drawback of cefuroxime in its inability to eradicate atypical pathogen.
It is yet another object of the present invention to provide a simple process for preparing oral solid dosage forms comprising pharmaceutical effective amounts of ofloxacin and cefuroxime or salts of thereof.
SUMMARY OF THE INVENTION
The present invention relates to a pharmaceutical composition for treatment of respiratory tract infections (RTIs), ear-nose-throat infections (ENTIs) and skin and skin structure infections (SSTIs). In the invention ofloxacin and cefuroxime or salts of thereof and excipients are used. Ofloxacin is used in 200 to 600 mg/tablet and cefuroxime or salts of thereof are used in 250 to 1000 mg/tablet and excipient are used in % quantity sufficient (Q.S.)

DETAILED DESCRIPTION
The present invention relates to a pharmaceutical composition for treatment of respiratory tract infections (RTIs), ear-nose-throat infections (ENTIs) and skin and skin structure infections (SSTIs) which comprises of ofloxacin and cefuroxime or salts of thereof.
Ofloxacin is a synthetic broad spectrum antimicrobial, belonging to group called fluoroquinolones which possesses the widest spectrum of activity and justifies its potential empiric use (90.6 %, range 87.1 % - 92.2 %) for respiratory tract, urinary tract and cutaneous infections. Ofloxacin is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA Gyrase, a type II topoisomerase and topoisomerase IV {Drlica K, Zhao Xep 1997). Microbial Mol Biol Rev 1997; 61(3): 377-92} which is an enzyme necessary to separate replicated DNA, there by inhibiting bacterial cell division.
The minimum inhibitory concentration (MIC) area (under the curve) (MIC/AUC) of ofloxacin is 1-2 mcg/mL for Streptococcus pneumoniae, and AUC (area under curve) is 96 mcg.hr/mL for 400 mg dose of ofloxacin {Lister PD &Sanders CC.Antimicrob Ag Chemother 1995; 43: 5: 1118-1134.}, the AUC/MIC is 48 to 96 which indicate unreliable efficacy in this regard. Ofloxacin is effective against Staphylococcus aureus and Staphylococcus epidermidis but has unreliable activity against Streptococcus pyogenes as well as Streptococcus pneumoniae. Ofloxacin provides the exclusive effective oral option for eradicating Pseudomonas aeruginosa by an oral antimicrobial dosing. The bioavailability of ofloxacin in tablet form is approximately 98% following oral administration reaching maximum serum concentration within one or two hours.
Cefuroxime is a semi-synthetic analog of second generation cephalosporin antibiotic which is extremely active against Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catarrhalis. {Kucer A et al. (Eds) 5th Ed 1997; Butterworth Heinemann pp 291-318; Verbist L & Dhoore F.Acta Clin Belg 1994; 49(6):268 - 273.}. In vitro studies have demonstrated cefuroxime to be better active against Gram-positive and Gram-negative organism than earlier generation cephalosporins such as cephalexin and cefaclor. Cefuroxime interfere with the cell wall synthesis in the bacteria.
Cefuroxime axetil and cefuroxime sodium are used in treating infections of upper and lower respiratory tract, skin and soft tissue infection, urinary tract infection, bone and joints infection and gonococcal infection. Cefuroxime sodium, in addition, is indicated in treating serious, pending bacteriological identification, meningitis prophylaxis against infection, in surgical procedure, urinary infection and patient with renal failure undergoing CAPD (continuous ambulatory peritoneal dialysis). Cefuroxime axetil is also used in treating and preventing Lyme disease.
In the present invention ofloxacin and cefuroxime or salts of thereof are used. Ofloxacin is used in 200 to 400 mg/tablet and cefuroxime or salts of thereof are used in 250 to 1000 mg/tablet.
Further in present invention other pharmaceutical excipients are used. The pharmaceutical composition of the present invention can be prepared according to techniques that are well known in pharmaceutical chemistry, comprising weighing, mixing, process of granulation, drying, compression and like.
The present invention is illustrated with the following examples:

Example 1:
Sr.No. Ingredient Amount/Tablet
1 Cefuroxime axetil
Equivalent to cefuroxime 250 mg
2 Ofloxacin 200 mg
3 Excipients Q.S.

Example 2:
Sr.No. Ingredient Amount/Tablet
1 Cefuroxime axetil
Equivalent to cefuroxime 250 mg
2 Ofloxacin 400 mg
3 Excipients Q.S.

Example 3:
Sr.No. Ingredient Amount/Tablet
1 Cefuroxime axetil
Equivalent to cefuroxime 250 mg
2 Ofloxacin 600 mg
3 Excipients Q.S.

Example 4:
Sr.No. Ingredient Amount/Tablet
1 Cefuroxime axetil
Equivalent to cefuroxime 500 mg
2 Ofloxacin 200 mg
3 Excipients Q.S.

Example 5:
Sr.No. Ingredient Amount/Tablet
1 Cefuroxime axetil
Equivalent to cefuroxime 500 mg
2 Ofloxacin 400 mg
3 Excipients Q.S.
Example 6:
Sr.No. Ingredient Amount/Tablet
1 Cefuroxime axetil
Equivalent to cefuroxime 500 mg
2 Ofloxacin 600 mg
3 Excipients Q.S.

Combination of ofloxacin and cefuroxime can constitute the first line empiric therapy in RTIs, ENTs and SSTIs.
It can be truly called as a broad spectrum antibacterial and it merits consideration for all those infections in which streptococci are possible infective pathogen along with atypical bacteria.
This combination is truly synergistic as even the mechanisms of action of both are distinctly different.
Cefuroxime compliments ofloxacin when the combination of two is advocated for RTI since it is more reliable against streptococci, whilst ofloxacin overcomes the drawback of cefuroxime in its inability to eradicate atypical pathogen.
The combination of ofloxacin and cefuroxime or salts of thereof offers an effective option in the treatment of RTIs, ENTs, and SSTIs.
ABSTRACT

The present invention relates to a pharmaceutical composition comprising ofloxacin and cefuroxime or salts of thereof and other pharmaceutical excipients. The present invention provides more reliable effect against most of bacteria. The invention makes up for the weakness of ofloxacin. The combination of ofloxacin and cefuroxime or salts of thereof offers an effective option in the treatment of RTIs, ENTs and SSTIs.