Cationic amphiphiles for intracellular delivery of therapeutic molecules and its composition, process and method of treatment
AssigneeCouncil of Scientific and Industrial Research
InventorsMajeti Bharat Kumar, Arabinda Chaudhuri, Yerramsetti Ramadas, Nalam Madhusudhana Rao
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Abstract
The present invention provides novel cationic amphiphiles capable of facilitating transport of biologically active molecules into cells wherein the said amphiphiles contain cyclic head group having polar functional groups and pharmaceutical composition useful for delivering biologically active therapeutic molecules into body cells.
Claims49
A bioactive cationic amphiphile represented by a general formula (I)
- 7
- wherein;
- R1 and R2 independently represent hydrogen atom or lipophilic moiety excluding the possible definition for R1 and R2 being simultaneously as hydrogen atom;
- R3 and R4 independently represent hydrogen or a polar group;
- n=1, 2 or 3;
- X=an inorganic or organic anion.
A bioactive cationic amphiphile as represented by general formula (II)
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- Wherein R1, R2, R3 and R4 independently or in combination represented as described below:
- n=1
- R1=R2=CH3—(CH2)10CH2—, CH3—(CH2)12CH2—, CH3—(CH2)14 CH2—, CH3—(CH2)16 CH2— and/or CH3—(CH2)7—CH═CH(CH2)7CH2.
- R3=R4=hydroxyl group.
A process for the preparation of bioactive cationic amphiphiles of formulae (I-II) said process comprising the steps of:
- (a) coupling an appropriate saturated or unsaturated lipophilic aliphatic bromide with saturated or unsaturated lipophilic aliphatic alkyl amine in polar aprotic solvents in presence of base to obtain the corresponding aliphatic hydrophobic secondary amine;
- (b) protecting both the terminal primary alcohol groups of an aliphatic alcohols containing additional polar functionalities with suitable protecting groups in polar aprotic solvent;
- (c) reacting the secondary amine obtained in step (a) with the primary hydroxyl protected aliphatic polar intermediate obtained in step (b) in polar aprotic solvents in presence of an organic base to obtain quaternized amphiphile compound;
- (d) passing the quaternized amphiphilic compound obtained in step (c) through anion-exchange column chromatography and eluting with a mixture of polar organic solvent to obtain the required cationic amphiphile.
A pharmaceutical composition for intracellular delivery of biologically active molecules, said composition comprising:
- at least a cationic amphiphile;
- a bioactive molecule;
- a colipid;
- and
- optionally an additive.
A method for intracellular delivery of biologically active molecules said method comprising administering to a subject at least one biologically active compound represented by the following structural formula:
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- wherein;
- R1 and R2 independently represent hydrogen atom or lipophilic moiety excluding the definition of R1 and R2 being simultaneously represented as hydrogen atom;
- R3 and R4 independently represent hydrogen or a polar group;
- n=1, 2, 3 or 4;
- X=an inorganic or organic anion.
Dependencies are inferred from the claim text.