Polymeric Drug-Delivery Material, Method for Manufacturing Thereof and Method for Delivery of a Drug-Delivery Composition

Abstract

A method for manufacturing a drug-delivery composition includes providing at least one pharmaceutically active compound, a dry powder comprising at least a polymer, and an aqueous solution. The dry powder, the pharmaceutically active compound and the aqueous solution are mixed to form a paste-like or semi-solid drug-delivery composition, wherein the aqueous solution is added in an amount of less than or equal to twice the total dry mass of the dry powder.

1 . A method for manufacturing a drug-delivery composition, comprising:
 providing at least one pharmaceutically active compound, a dry powder comprising at least a polymer, and an aqueous solution;   mixing the dry powder, the pharmaceutically active compound and the aqueous solution to form a paste-like or semi-solid drug-delivery composition, wherein the aqueous solution is added in an amount less than or equal to twice the total dry mass of the dry powder.   
     
     
         2 . The method according to  claim 1 , wherein the added amount of the aqueous solution is less than or equal to the total dry mass of the dry powder mixture. 
     
     
         3 . The method according to  claim 1 , further comprising:
 providing the pharmaceutically active compound as dry pharmaceutically active compound powder; and   homogeneously mixing the dry polymer powder with the dry pharmaceutically active compound to prepare a dry powder mixture before adding the aqueous solution.   
     
     
         4 . The method according to  claim 3 , wherein the dry pharmaceutically active compound powder comprises at least the pharmaceutically active compound and at least one excipient selected from the group consisting of monosaccharides, disaccharides, oligosaccharides, polysaccharides like hyaluronic acid, pectin, gum arabic and other gums, albumin, chitosan, collagen, collagen-n-hydroxysuccinimide, fibrin, fibrinogen, gelatin, globulin, polyaminoacids, polyurethane comprising amino acids, prolamin, protein-based polymers, copolymers and derivatives thereof, and mixtures thereof. 
     
     
         5 . The method according to  claim 1 , wherein the aqueous solution is added step-wise to form the drug-delivery composition. 
     
     
         6 . The method according to  claim 1 , wherein the formation of the paste-like or semi-solid drug-delivery composition includes repeated cycles of pressing and folding in an algorithmic manner of the mixture of the dry powder, the pharmaceutically active compound and the aqueous solution. 
     
     
         7 . The method according to  claim 6 , wherein the aqueous solution is added step-wise during pressing and folding. 
     
     
         8 . The method according to  claim 6 , wherein the pressing applies a pressure of not more than 10 6  N·m −2 . 
     
     
         9 . The method according to  claim 1 , wherein the dry powder is mixed at least with a portion of the aqueous solution before the dry pharmaceutically active compound is added. 
     
     
         10 . The method according to  claim 1 , wherein the pharmaceutically active compound is solved in the aqueous solution before being mixed with the dry powder. 
     
     
         11 . The method according to  claim 1 , further comprising:
 mixing the dry powder and the aqueous solution to form a paste-like or semi-solid mass; and   adding the pharmaceutically active compound to the paste-like or semi-solid mass to form the paste-like or semi-solid drug-delivery composition.   
     
     
         12 . The method according to  claim 11 , wherein the pharmaceutical active compound is added as solution. 
     
     
         13 . The method according to  claim 1 , wherein the pharmaceutical active compound is provided as powder comprising particles in a range from about 100 nm to about 50 μm. 
     
     
         14 . The method according to  claim 1 , wherein the polymer is a hydrophilic polymer that swells when mixed with the aqueous solution. 
     
     
         15 . The method according to  claim 1 , wherein the polymer has a molecular weight of at least 10 kDa. 
     
     
         16 . The method according to  claim 1 , wherein the pharmaceutically active compound is selected from a group consisting of immunoglobulins, fragments or fractions of immunoglobulins, synthetic substance mimicking immunoglobulins or fragments or fractions thereof, peptides having a molecular mass equal to or higher than 3 kDa, ribonucleic acids (RNA), desoxyribonucleic acids (DNA), plasmids, peptide nucleic acids (PNA), steroids, and corticosteroids. 
     
     
         17 . The method according to  claim 1 , wherein the pharmaceutically active compound is selected from the group consisting of: immunoglobulins, fragments or fractions of immunoglobulins, synthetic substance mimicking immunoglobulins or synthetic, semisynthetic or biosynthetic fragments or fractions thereof, chimeric, humanized or human monoclonal antibodies, Fab fragments, fusion proteins or receptor antagonists (e.g., anti-TNF alpha, Interleukin- 1 , Interleukin-6 etc.), antiangiogenic compounds (e.g., anti-VEGF, anti-PDGF etc.), intracellular signaling inhibitors (e.g JAK1,3 and SYK inhibitors) peptides having a molecular mass equal to or higher than 3 kDa, ribonucleic acids (RNA), desoxyribonucleic acids (DNA), plasmids, peptide nucleic acids (PNA), steroids, corticosteroids, an adrenocorticostatic, an antibiotic, an antidepressant, an antimycotic, a [beta]-adrenolytic, an androgen or antiandrogen, an antianemic, an anabolic, an anaesthetic, an analeptic, an antiallergic, an antiarrhythmic, an antiarterosclerotic, an antibiotic, an antifibrinolytic, an anticonvulsive, an antiinflammatory drug, an anticholinergic, an antihistaminic, an antihypertensive, an antihypotensive, an anticoagulant, an antiseptic, an antihemorrhagic, an antimyasthenic, an antiphlogistic, an antipyretic, a beta-receptor antagonist, a calcium channel antagonist, a cell, a cell differentiation factor, a chemokine, a chemotherapeutic, a coenzyme, a cytotoxic agent, a prodrug of a cytotoxic agent, a cytostatic, an enzyme and its synthetic or biosynthetic analogue, a glucocorticoid, a growth factor, a haemostatic, a hormone and its synthetic or biosynthetic analogue, an immunosuppressant, an immunostimulant, a mitogen, a physiological or pharmacological inhibitor of mitogens, a mineralcorticoid, a muscle relaxant, a narcotic, a neurotransmitter, a precursor of a neurotransmitter, an oligonucleotide, a peptide, a (para)-sympathicomimetic, a (para)-sympatholytic, a protein, a sedating agent, a spasmolytic, a vasoconstrictor, a vasodilatator, a vector, a virus, a virus-like particle, a virustatic, a wound-healing substance, and combinations thereof. 
     
     
         18 . The method according to  claim 1 , further comprising:
 forming the drug-delivery composition into an applicable form.   
     
     
         19 . The method according to  claim 1 , wherein the polymer is selected from the group consisting of, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), gelatin, collagen, starch, cellulose, chitosan, albumin, fibrin, fibrinogen, pectin, gum arabic and other gums, carrageenan, hyaluronic acid, polyethyleneimine, protamin, therapeutic proteins and peptides, nucleic acids, ribonucleic acids and derivatives thereof 
     
     
         20 . A drug-delivery composition, comprising:
 a paste-like or semi-solid mixture comprising at least a polymer, a pharmaceutically active compound, and an aqueous solution, wherein the total amount of the aqueous solution in the paste-like or semi-solid mixture is less than or equal to twice the total dry mass of the mixture.   
     
     
         21 . The drug-delivery composition according to  claim 20 , wherein the total amount of the aqueous solution is less than or equal to the total dry mass of the mixture. 
     
     
         22 . The drug-delivery composition according to  claim 20 , wherein the aqueous solution comprises water and electrolyte. 
     
     
         23 . The drug-delivery composition according to  claim 20 , wherein the paste-like or semi-solid mixture has a modulus of elasticity at least of 10 −4  N·mm −2 . 
     
     
         24 . The drug-delivery composition according to  claim 20 , wherein the paste-like or semi-solid mixture has a viscosity of at least 100 mPa·s. 
     
     
         25 . The drug-delivery composition according to  claim 20 , wherein the pharmaceutically active compound is selected from the group consisting of immunoglobulins, fragments or fractions of immunoglobulins, synthetic substance mimicking immunoglobulins or fragments or fractions thereof, therapeutic proteins, peptides having a molecular mass equal to or higher than 3 kDa, ribonucleic acids (RNA), desoxyribonucleic acids (DNA), plasmids, peptide nucleic acids (PNA), steroids, and corticosteroids. 
     
     
         26 . The drug-delivery composition according to  claim 20 , wherein the pharmaceutically active compound is selected from the group consisting of immunoglobulins, fragments or fractions of immunoglobulins, synthetic substance mimicking immunoglobulins or synthetic, semisynthetic or biosynthetic fragments or fractions thereof, chimeric, humanized or human monoclonal antibodies, Fab fragments, fusion proteins or receptor antagonists (e.g., anti TNF-alpha, Interleukin-1, Interleukin-6 etc.), antiangiogenic compounds (e.g., anti-VEGF, anti-PDGF etc.), intracellular signaling inhibitors (e.g JAK1,3 and SYK inhibitors) peptides having a molecular mass equal to or higher than 3 kDa, ribonucleic acids (RNA), desoxyribonucleic acids (DNA), plasmids, peptide nucleic acids (PNA), steroids, corticosteroids, an adrenocorticostatic, an antibiotic, an antidepressant, an antimycotic, a [beta]-adrenolytic, an androgen or antiandrogen, an antianemic, an anabolic, an anaesthetic, an analeptic, an antiallergic, an antiarrhythmic, an antiarterosclerotic, an antibiotic, an antifibrinolytic, an anticonvulsive, an antiinflammatory drug, an anticholinergic, an antihistaminic, an antihypertensive, an antihypotensive, an anticoagulant, an antiseptic, an antihemorrhagic, an antimyasthenic, an antiphlogistic, an antipyretic, a beta-receptor antagonist, a calcium channel antagonist, a cell, a cell differentiation factor, a chemokine, a chemotherapeutic, a coenzyme, a cytotoxic agent, a prodrug of a cytotoxic agent, a cytostatic, an enzyme and its synthetic or biosynthetic analogue, a glucocorticoid, a growth factor, a haemostatic, a hormone and its synthetic or biosynthetic analogue, an immunosuppressant, an immunostimulant, a mitogen, a physiological or pharmacological inhibitor of mitogens, a mineralcorticoid, a muscle relaxant, a narcotic, a neurotransmitter, a precursor of a neurotransmitter, an oligonucleotide, a peptide, a (para)-sympathicomimetic, a (para)-sympatholytic, a protein, a sedating agent, a spasmolytic, a vasoconstrictor, a vasodilatator, a vector, a virus, a virus-like particle, a virustatic, a wound-healing substance, and combinations thereof. 
     
     
         27 . A method for delivery of a drug-delivery composition, comprising:
 providing a drug-delivery composition comprising a paste-like or semi-solid mixture comprising at least a polymer, a pharmaceutically active compound, and an aqueous solution, wherein the total amount of the aqueous solution in the paste-like or semi-solid mixture is less than or equal to twice the total dry mass of the mixture;   applying the drug-delivery composition into a human or animal body.   
     
     
         28 . The method of  claim 27 , wherein applying the mixture into the human or animal body comprises at least one of:
 implanting or injecting the mixture into a human or animal body;   intraocular injecting the mixture into a human, or animal body;   subcutaneous injecting the mixture into a human, or animal body;   intramuscular injecting the mixture into a human, or animal body;   intraperitoneal injecting the mixture into a human, or animal body;   intravenously injecting the mixture into a human, or animal body;   administration of the mixture into a human or animal body by inhalation or intranasal application;   intravenously injecting the mixture into a human or animal body; and   administration of the mixture into a human or animal body by inhalation or intranasal application.