Preparations for the external application of antiseptic agents and/or agents promoting the healing of wounds

Abstract

The present invention relates to liposomal pharmaceutical preparations which include active agents such as antiseptic agents, wound-healing agents, or combinations thereof, useful in the treatment of external wounds. The active agents are encapsulated in liposomes, and the liposomes are incorporated in pharmaceutical preparations such as liquids, ointments, gels, lotions, or creams capable of delivering the active agents to external wound sites. The invention further relates to methods of preparation of the liposomes and the pharmaceutical preparations, and to methods of treatment of external wounds and ophthalmic infections.

1 . A pharmaceutical preparation for external application comprising an antiseptic agent, a wound-healing agent, or a combination thereof, encapsulated in a plurality of liposomes. 
     
     
         2 . A pharmaceutical preparation according to  claim 1 , further comprising a pharmaceutically acceptable vehicle, wherein a portion of said antiseptic agent or said wound-healing agent, or said combination thereof contained in the preparation is not encapsulated in said liposomes. 
     
     
         3 . A pharmaceutical preparation according to  claim 2 , wherein at least the greatest part of said antiseptic agent or said wound healing promoting agent, or said combination thereof, is encapsulated inside the liposomes. 
     
     
         4 . A pharmaceutical preparation according to  claim 1  wherein said antiseptic agent is selected from the group consisting of metal compounds such as mercury compounds, phenol derivatives such as thymol, eugenol and hexachlorophene, detergents, iodine and iodine complexes. 
     
     
         5 . A pharmaceutical preparation according to  claim 4  wherein said antiseptic agent is povidone iodine. 
     
     
         6 . A pharmaceutical preparation according to  claim 1  wherein said wound-healing agent is selected from the group consisting of allantoin, an azulene compound, a compound from the vitamin B series, and combinations of the foregoing. 
     
     
         7 . A pharmaceutical preparation according to  claim 1  wherein the preparation contains at least one antiseptic and at least one wound healing promoting agent. 
     
     
         8 . A pharmaceutical preparation according to  claim 1  wherein said liposomes are of a substantially uniform size in the range from about 20 to about 20,000 nm. 
     
     
         9 . A pharmaceutical preparation according to  claim 8  wherein said liposomes are of a substantially uniform size in the range from about 50 to about 4,000 nm. 
     
     
         10 . A pharmaceutical preparation according to  claim 8  wherein said liposomes are of a substantially uniform size in the range from about 500 to about 2,500 nm. 
     
     
         11 . A pharmaceutical preparation according to  claim 8  wherein said liposomes are of a substantially uniform size of about 1,000 nm diameter. 
     
     
         12 . A pharmaceutical preparation according to  claim 2  wherein the preparation releases said antiseptic agent, said wound-healing agent, or combination thereof, in an environment of use over an extended time period. 
     
     
         13 . A pharmaceutical preparation according to  claim 12  wherein said extended time period comprises several hours duration. 
     
     
         14 . A pharmaceutical preparation according to  claim 12  wherein the preparation releases said antiseptic agent, said wound-healing agent, or combination thereof, at approximately the same release rate over the release time period. 
     
     
         15 . A pharmaceutical preparation according to  claim 2  further comprising at least one anesthetically active agent. 
     
     
         16 . A pharmaceutical preparation according to  claim 2  further comprising conserving agents and consistency forming additives. 
     
     
         17 . A pharmaceutical preparation according to  claim 2 , wherein said vehicle is a liquid and said preparation is in the form of a solution or dispersion comprising liposomes. 
     
     
         18 . A pharmaceutical preparation according to  claim 17 , wherein said preparation is in the form of a pharmaceutical drop preparation. 
     
     
         19 . A pharmaceutical preparation according to  claim 2 , wherein said vehicle comprises a hydrophilic, lipophilic, or amphophilic cream base and said preparation is in the form of a cream. 
     
     
         20 . A pharmaceutical preparation according to  claim 2 , in the form of a pharmaceutical oil in water or a water in oil lotion. 
     
     
         21 . A pharmaceutical preparation according to  claim 2 , wherein said vehicle is an ointment base and the preparation is in the form of a pharmaceutical ointment. 
     
     
         22 . A pharmaceutical preparation according to  claim 2 , wherein said vehicle is a gel base and the preparation is in the form of a pharmaceutical gel. 
     
     
         23 . A pharmaceutical preparation according to  claim 22 , wherein said vehicle is a nonalcoholic hydrogel base. 
     
     
         24 . A pharmaceutical preparation according to  claim 2 , wherein the pharmaceutical preparation is in the form of a pharmaceutical eyedrop formulation;
 wherein said liposomes comprise a pharmaceutically acceptable liposome membrane forming substance;   wherein said antiseptic agent comprises a 0.1 to 2% PVP iodine solution at least most of which is encapsulated within said liposomes; and   wherein said liposomes are of substantially uniform size between about 50 and about 4,000 nM, and said formulation may additionally comprise customary additives, adjuvants and auxiliary substances of a pharmaceutical eyedrop formulation.   
     
     
         25 . A pharmaceutical preparation according to  claim 24  wherein said liposomes are of substantially uniform size, with diameters of about 1,000 nm. 
     
     
         26 . A method of preparing a liposomal pharmaceutical formulation comprising the steps of:
 dissolving a liposome forming agent in a solvent in a suitable container;   evaporating said solvent to form a lipid film on the inner surface of said container;   adding a quantity of PVP iodine solution with said lipid film therein to form a mixture;   agitating said mixture to produce liposomes;   separating said liposomes;   dispersing said liposomes in a sodium chloride buffer solution; and freeze-drying said dispersion.   
     
     
         27 . A method of preparing a liposomal pharmaceutical formulation according to  claim 26 , further comprising the step of filtering said dispersion or said mixture through a high pressure filtering means subsequent to liposome formation. 
     
     
         28 . A method of treating external wounds comprising the steps of:
 applying an antiseptically active amount of a pharmaceutical preparation to an external wound, wherein said pharmaceutical preparation comprises an antiseptic agent, a wound-healing agent, or a combination thereof, encapsulated in a plurality of liposomes dispersed in a pharmaceutically acceptable vehicle.   
     
     
         29 . A method of treating eye infections comprising the steps of:
 applying an antiseptically effective dose of a pharmaceutical preparation to the eye of a mammal having an eye infection, wherein said pharmaceutical preparation comprises an antiseptic agent, a wound-healing agent, or a combination thereof, encapsulated in a plurality of liposomes and dispersed in a pharmaceutically acceptable vehicle.   
     
     
         30 . A method of treating eye infections as recited in  claim 29 .
 wherein said pharmaceutical preparation is in the form of a pharmaceutical eyedrop formulation;   wherein said liposomes comprise a pharmaceutically acceptable liposome membrane forming substance;   wherein said antiseptic agent comprises a 0.1 to 2% PVP iodine solution at least most of which is encapsulated within said liposomes; and   wherein said liposomes are of substantially uniform size between about 50 and about 4,000 nm, and said formulation may additionally comprise customary additives, adjuvants and auxiliary substances of a pharmaceutical eyedrop formulation.