Method for the improvement of transport across adaptable semi-permeable barriers

A method for controlling the flux of penetrants across an adaptable semi-permeable porous barrier, the method comprising the steps of:

• preparing a formulation by suspending or dispersing said penetrants in a polar liquid, the penetrants comprising at least two kinds or forms of amphiphilic substances with a tendency to aggregate, wherein said at least two substances differ by at least a factor of 10 in solubility in said polar liquid, and wherein said penetrants are able to transport a drug agent through the pores of said barrier or enable drug agent permeation through the pores of said barrier after the penetrants have entered the pores, the formulation further comprising a thickening agent and at least one antioxidant;
• selecting a dose amount of said penetrants to be applied on a predetermined area of said barrier to control the flux of said penetrants across said barrier;
• and
• applying said formulation containing a selected dose amount of said penetrants onto said area of said porous barrier, the formulation having a viscosity that enables retention of the drug agent at the area, wherein the at least one antioxidant reduces an increase of oxidation index to less than 100% per 12 months, and
• wherein the drug agent is a peptide or a protein.

A method for controlling the flux of penetrants across an adaptable semi-permeable porous barrier, the method comprising the steps of:

• preparing a formulation by suspending or dispersing said penetrants in a polar liquid, the penetrants comprising at least two kinds or forms of amphiphilic substances with a tendency to aggregate, wherein said at least two substances differ by at least a factor of 10 in solubility in said polar liquid, and wherein said penetrants are able to transport a drug agent through the pores of said barrier or enable drug agent permeation through the pores of said barrier after the penetrants have entered the pores, the formulation further comprising a thickening agent and at least one antioxidant;
• selecting a dose amount of said penetrants to be applied on a predetermined area of said barrier to control the flux of said penetrants across said barrier;
• and
• applying said formulation containing the selected dose amount of said penetrants onto said area of said porous barrier, the formulation having a viscosity that enables retention of the drug agent at the area, wherein the at least one antioxidant reduces the increase of oxidation index to less than 50% per 12 months and
• wherein the drug agent is a peptide or a protein.

A method for controlling the flux of penetrants across an adaptable semi-permeable porous barrier, the method comprising the steps of:

• preparing a formulation by suspending or dispersing said penetrants in a polar liquid, the penetrants comprising at least two kinds or forms of amphiphilic substances with a tendency to aggregate, wherein said at least two substances differ by at least a factor of 10 in solubility in said polar liquid, and wherein said penetrants are able to transport a drug agent through the pores of said barrier or enable drug agent permeation through the pores of said barrier after the penetrants have entered the pores, the formulation further comprising a thickening agent and at least one microbicide;
• selecting a dose amount of said penetrants to be applied on a predetermined area of said barrier to control the flux of said penetrants across said barrier;
• and
• applying said formulation containing the selected dose amount of said penetrants onto said area of said porous barrier, the formulation having a viscosity that enables retention of the drug agent at the area, wherein said at least one microbicide is added in an amount that reduces the bacterial count of 1 million germs added per g of total mass of the formulation to less than 100 in the case of aerobic bacteria, to less than 10 in the case of entero-bacteria, and to less than 1 in the case of Pseudomonas aeruginosa or Staphylococcus aureus, after a period of 3 days and
• wherein the drug agent is a peptide or a protein.

A method for controlling the flux of penetrants across an adaptable semi-permeable porous barrier, the method comprising the steps of:

• preparing a formulation by suspending or dispersing said penetrants in a polar liquid, the penetrants comprising at least two kinds or forms of amphiphilic substances with a tendency to aggregate, wherein said at least two substances differ by at least a factor of 10 in solubility in said polar liquid, and wherein said penetrants are able to transport a drug agent through the pores of said barrier or enable drug agent permeation through the pores of said barrier after the penetrants have entered the pores, the formulation further comprising a thickening agent;
• selecting a dose amount of said penetrants to be applied on a predetermined area of said barrier to control the flux of said penetrants across said barrier;
• and
• applying said formulation containing the selected dose amount of said penetrants onto said area of said porous barrier, the formulation having a viscosity that enables retention of the drug agent at the area, wherein said thickening agent is selected from the class of pharmaceutically acceptable hydrophilic polymers consisting of partially etherified cellulose derivatives;
• completely synthetic hydrophilic polymers;
• natural gums comprising alginates, carrageenans, guar-gums, gelatines, tragacanths, amidated pectins, xanthans, chitosan, collagens, agaroses;
• mixtures and further derivatives or co-polymers thereof, and
• wherein the drug agent is a peptide or a protein.

A method for controlling the flux of penetrants across an adaptable semi-permeable porous barrier, the method comprising the steps of:

• preparing a formulation by suspending or dispersing said penetrants in a polar liquid, the penetrants comprising at least two kinds or forms of amphiphilic substances with a tendency to aggregate, wherein said at least two substances differ by at least a factor of 10 in solubility in said polar liquid, and wherein said penetrants are able to transport a drug agent through the pores of said barrier or enable drug agent permeation through the pores of said barrier after the penetrants have entered the pores, the formulation further comprising a thickening agent and at least one antioxidant:
• selecting a dose amount of said penetrants to be applied on a predetermined area of said barrier to control the flux of said penetrants across said barrier;
• and
• applying said formulation containing the selected dose amount of said penetrants onto said area of said porous barrier, the formulation having a viscosity that enables retention of the drug agent at the area, wherein said at least one antioxidant is selected from synthetic phenolic antioxidants;
• aromatic amines;
• phenols and phenolic acids, protocatechuic acid, quinic acid, syringic acid, ellagic acid, salicylic acid, nordihydroguaiaretic acid (NDGA), eugenol;
• tocopherols and their derivatives;
• trolox and corresponding amide- and thiocarboxamide analogues;
• ascorbic acid esters, ascorbic acid and its salts, isoascorbate, (2 or 3 or 6)-o-alkylascorbic acids, ascorbyl esters;
• non-steroidal anti-inflammatory agents (NSAIDs);
• sodium bisulphate, sodium metabisulphite, thiourea;
• chelating agents;
• glucose, ubiquinol-10;
• enzymatic antioxidants;
• flavonoids;
• cystein, N-acetylcystein, mesna, glutathione, thiohistidine derivatives, triazoles;
• monothioglycerol, NDGA, tannins, cinnamic acid, hydroxycinnamatic acids and their esters;
• spice extracts;
• citric acid;
• camosic acid, camosol, carsolic acid;
• rosmarinic acid, rosmarindiphenol, gentisic acid, ferulic acid;
• oat flour extracts;
• thioethers, dithioethers, sulphoxides, tetralkyithiuram disulphides;
• phytic acid, steroid derivatives;
• tryptophan metabolites;
• organochalcogenides;
• and oxidation suppressing enzymes, and
• wherein the drug agent is a peptide or a protein.

A method for controlling the flux of penetrants across an adaptable semi-permeable porous barrier, the method comprising the steps of:

• preparing a formulation by suspending or dispersing said penetrants in a polar liquid, the penetrants comprising at least two kinds or forms of amphiphilic substances with a tendency to aggregate, wherein said at least two substances differ by at least a factor of 10 in solubility in said polar liquid, and wherein said penetrants are able to transport a drug agent through the pores of said barrier or enable drug agent permeation through the pores of said barrier after the penetrants have entered the pores, the formulation further comprising a thickening agent and at least one microbicide;
• selecting a dose amount of said penetrants to be applied on a predetermined area of said barrier to control the flux of said penetrants across said barrier;
• and
• applying said formulation containing the selected dose amount of said penetrants onto said area of said porous barrier, the formulation having a viscosity that enables retention of the drug agent at the area, wherein said at least one microbicide is selected from short chain alcohols, hexachlorophene;
• phenolic compounds;
• triclosan, parabens;
• acids;
• quaternary ammonium compounds;
• phenoalkecinium salt;
• mercurium compounds;
• chlorhexidine or its gluconate;
• antibiotically active compounds of biological origin, and mixtures thereof, and
• wherein the drug agent is a peptide or a protein.

A method for controlling the flux of penetrants across an adaptable semi-permeable porous barrier, the method comprising the steps of:

• preparing a formulation by suspending or dispersing said penetrants in a polar liquid, the penetrants comprising at least two kinds or forms of amphiphilic substances with a tendency to aggregate, wherein said at least two substances differ by at least a factor of 10 in solubility in said polar liquid, and wherein said penetrants are able to transport a drug agent through the pores of said baffler or enable drug agent permeation through the pores of said bamer after the penetrants have entered the pores, the formulation further comprising a thickening agent;
• selecting a dose amount of said penetrants to be applied on a predetermined area of said barrier to control the flux of said penetrants across said barrier;
• and
• applying said formulation containing the selected dose amount of said penetrants onto said area of said porous barrier, the formulation having a viscosity that enables retention of the drug agent at the area, wherein the less soluble amongst the aggregating substances is a lipid and the substance which is more soluble in the suspending liquid is a surfactant, and
• wherein the drug agent is a pevtide or a protein.

A method for increasing the flux of a penetrant across the skin or mucosa of a human or animal, the method comprising:

• (a) applying a formulation onto a predetermined area of the skin or mucosa, the formulation comprising a penetrant, a polar liquid, and a thickening agent and having a viscosity that is 0.2 kN s/m2 to 5 kN s/m2 the penetrant (i) comprising a phosphatidyicholine and a surfactant and (ii) being capable of transporting a drug agent across the skin or mucosa, wherein the formulation is applied at a selected dose amount of the penetrant per area of the skin or mucosa of a human or animal, the formulation having a viscosity that enables retention of the drug agent at the area;
• and
• (b) enlarging the applied dose amount of penetrant per area of the skin or mucosa of a human or animal,
• wherein the drug agent is a peptide or a protein.