Title of Invention

CROSS-LINKED CHITOSAN-GELATIN COATED LIPOSOMAL FORMULATIONS

Abstract Liposomes containing phosphatidylcholine and cholesterol and coated by mixture of chitosan and gelatin were prepared by double emulsification method. The invention relate to formulate and characterize liposomes of camptothecin (CPT)-11-HCI (Irinotecan HCl) containing chitosan, gelatin, and both polymers as coating materials; and also to increase its circulation longevity when compared with the free drug while maintaining the agent in its active lactone form.
Full Text FORM-2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
PROVISIONAL
Specification
(See section 10 and rule 13)


THE FOLLOWING SPECIFICATION DESCRIBES THE INVENTION.
The present invention provides a composition and method for delivering as irinotecan to a mammalian host. The composition and method are characterized by 1) ability to administer drug in oral dosage form, 2) high drug and liposome stability, 3) avoidance of solubility problems, 4) reduced drug toxicity 5) increased therapeutic efficacy of the drug, and 6) modulation of multidrug resistance in cancer cells. Liposomes were coated for chitosan-gelatin mixture and tested for particle size, surface morphology, entrapment efficiency, zeta potential, in vitro and in vivo release, DSC, ATR-FTIR, and stability studies. Results showed coating on liposomes were effective for stomach specific controlled release of CPT-11.



FORM - 2
THE PATENTS ACT, 1970
(39 of 1970)
8B
THE PATENTS RULES, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rule 13)
1. Title of the invention:
Cross-linked chitosan-gelatin coated liposomal formulations
2. Applicants):
(a) NAME: Shende Pravin Keshaorao, Gaud R.S.
(b) NATIONALITY: INDIAN
(c) ADDRESS: School of Pharmacy and Technology Management,
SVKM's NMIMS University, V M Mehta Road, Vile Parle (W), Mumbai-400056 (India).
3. PREAMBLE TO THE DESCRIPTION
Irinotecan HCI (7-ethyI-10-(4-[l-piperidino]-l-piperidino) carboxylcamptothecin HCl, CPT-11- HCl) is a water-soluble prodrug that can be converted to SN-38, an active metabolite that exhibits antitumor activity and treats breast cancer via the inhibition of topoisomerase I activity. The basic labile characteristic of the lactone ring in irinotecan is reversible and pH-dependent hydrolysis yields the inactive carboxylate species. Only lactone species can inhibit topoisomerase I, but this active molecule is very rarely found under physiological conditions. Liposomes have been extensively used as drug carriers. It has been asserted that the liposomal formulation of irinotecan HCl, can reduce the clearance of liposomes in vivo and increase anti-tumor activity. The invention relates to a method of oral formulation of irinotecan HCl encapsulated in chitosan-gelatin coated liposomes in presence of mixture of cross-linking agent sodium tripolyphosphate and sodium citrate for stomach specific release. This stomach specific oral formulation of irinotecan HCl can improve the safety and convenience by keeping in lactone form.

THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED.
Irinotecan and its active metabolite, SN-38, inhibit the action of topoisomerase I, an enzyme that produces reversible single-strand breaks in DNA during DNA replication. These single-strand breaks relieve torsional strain and allow DNA replication to proceed. Irinotecan and SN-38 bind to the topoisomerase I-DNA complex and prevent religation of the DNA strand, resulting in double-strand DNA breakage and cell death. In the liver, CPT-11 is enzymatically hydrolyzed by carbonylesterase to the active metabolite, SN-38. To overcome the inconvenience and the discomfort of the patient associated with parenteral administration, improve efficacy by reducing side effects and protect from photo degradation, alginate coated liposomes of CPT-11 for stomach specific release is invented. The invention relates to a method of oral formulation of irinotecan HC1 encapsulated in chitosan-gelatin coated liposomes in presence of mixture of cross-linking agent sodium tripolyphosphate and sodium citrate for stomach specific release. This stomach specific oral formulation of irinotecan HC1 can improve the safety and convenience by keeping in lactone form.
Coated liposomes were prepared by double emulsification method using sealed type homogenizer and chloroform/ethanol solvent system with alpha tocopherol as antioxidant. The liposomes were coated with chitosan-gelatin mixture in presence of cross-linking agent TPP- citrate under agitation with a magnetic stirrer at 800 rpm at ambient temperature. Different batches with different levels of cholesterol, phosphatidylcholine, calcium chloride were prepared and evaluated for particle size, surface morphology, entrapment efficiency, physicochemical interaction between drug and excipients, zeta potential and release studies. Accelerated stability studies were carried out for three months.

Documents:

2271-MUM-2008-ABSTRACT(14-12-2012).pdf

2271-MUM-2008-ABSTRACT(2-7-2009).pdf

2271-MUM-2008-CLAIMS(2-7-2009).pdf

2271-MUM-2008-CLAIMS(AMENDED)-(14-12-2012).pdf

2271-MUM-2008-CORRESPONDENCE(2-7-2009).pdf

2271-MUM-2008-DESCRIPTION(COMPLETE)-(2-7-2009).pdf

2271-mum-2008-description(provisional).doc

2271-mum-2008-description(provisional).pdf

2271-mum-2008-form 1.pdf

2271-mum-2008-form 2(2-7-2009).pdf

2271-MUM-2008-FORM 2(TITLE PAGE)-(14-12-2012).pdf

2271-MUM-2008-FORM 2(TITLE PAGE)-(2-7-2009).pdf

2271-mum-2008-form 2(title page)-(provisional)-(22-10-2008).pdf

2271-mum-2008-form 2(title page).pdf

2271-mum-2008-form 2.doc

2271-mum-2008-form 2.pdf

2271-MUM-2008-REPLY TO EXAMINATION REPORT(14-12-2012).pdf

2271-MUM-2008-SPECIFICATION(AMENDED)-(14-12-2012).pdf


Patent Number 258777
Indian Patent Application Number 2271/MUM/2008
PG Journal Number 06/2014
Publication Date 07-Feb-2014
Grant Date 06-Feb-2014
Date of Filing 22-Oct-2008
Name of Patentee SHENDE PRIVIN KESHAORAO
Applicant Address SCHOOL OF PHARMACY AND TECHNOLOGY MANAGEMENT, SVKM'S NMIMS UNIVERSITY, V. M. MEHTA ROAD, VILE PARLE (W), MUMBAI-56, INDIA.
Inventors:
# Inventor's Name Inventor's Address
1 SHENDE PRIVIN KESHAORAO SCHOOL OF PHARMACY AND TECHNOLOGY MANAGEMENT, SVKM'S NMIMS UNIVERSITY, V. M. MEHTA ROAD, VILE PARLE (W), MUMBAI-56, INDIA.
2 GAUD. R. S. SCHOOL OF PHARMACY AND TECHNOLOGY MANAGEMENT, SVKM'S NMIMS UNIVERSITY, V. M. MEHTA ROAD, VILE PARLE (W), MUMBAI-56, INDIA.
PCT International Classification Number A61K31/496; A61K31/519; A61K31/522
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA