Delivery system for biological component

Abstract

A controlled release delivery system composition and method applied to humans and animals, for oral, anal or vaginal administration of a biological component is disclosed. Preferably, a bacterium is delivered, and more preferably the bacterium is probiotic in nature, however, the biological component is not limited to the bacterium.

1 . A delivery system for a biological component comprising: 
 a delivery vehicle; and    a delivered component, the delivered component including the biological component.    
     
     
         2 . The delivery system of  claim 1  wherein the delivery vehicle is a hydrophilic agent, the hydrophilic agent selected from at least one of the group consisting of a starch, a polymer, a polysaccharide, a polypeptide, a cellulose derivative, an algae derivative and a gum.  
     
     
         3 . The delivery system of  claim 1  wherein the delivery vehicle is a hydrophilic agent, the hydrophilic agent selected from at least one of the group consisting of: 
 a) a starch selected from the group consisting of rice, corn and potato starch;    b) a gum selected from the group consisting of tragacanth gum, locust beam gum, acacia gum, guar gum, xanthan gum, ghatti gum and galactomannan gum;    c) an algae derivative selected from the group consisting of alginic acid, sodium alginate, agar, dextran and carageenan;    d) a polysaccharide selected from the group consisting of pectin and maltodextrin;    e) a cellulose derivative selected from the group consisting of methylcellulose, carboxymethylcellulose, sodium starch glycollate, sodium or calcium carboxymethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose, ethylhydroxy ethylcellulose, ethylmethylcellulose, hydroxyethylcellulose, cellulose acetate phthalate, hydroxypropyl cellulose and microcrystalline cellulose;    f) a desiccant selected from the group consisting of silica, aluminum silicate, magnesium silicate, aluminum magnesium silicate, sodium silicate and feldspar;    g) aluminum hydroxide;    h) a polypeptide selected from the group consisting of gelatin, collagen, casein and heterogeneous protein mixture; and    i) a polymer selected from the group consisting of acrylate, carboxypolymethylene, a polyalkylene glycol and polyvinylpyrrolidone.    
     
     
         4 . The delivery system of  claim 1  or  2  wherein the system is a dosage form as a monolithic tablet.  
     
     
         5 . The delivery system of  claim 1  or  2  wherein the system is a dosage form as a capsule.  
     
     
         6 . The delivery system of  claim 1  or  2  wherein the system is a dosage form as a wafer.  
     
     
         7 . The delivery system of  claim 1  or  2  wherein the system is an oral delivery system.  
     
     
         8 . The delivery system of  claim 1  or  2  wherein the system is an anal delivery system.  
     
     
         9 . The delivery system of  claim 1  or  2  wherein the system is a vaginal delivery system.  
     
     
         10 . The delivery system of  claim 1  or  2  wherein the biological component includes at least a bacteria.  
     
     
         11 . The delivery system of  claim 1  wherein the delivery vehicle is a hydrophobic agent, the hydrophobic agent selected from at least one of the group consisting of a wax and an inert material.  
     
     
         12 . The delivery system of  claim 11  wherein the hydrophobic agent is a wax, the wax selected from at least one of the group consisting of bees wax, paraffin and carnauba wax.  
     
     
         13 . The delivery system of  claim 11  wherein the hydrophobic agent is an inert material, the inert material being ethylcellulose.  
     
     
         14 . The delivery system of  claim 11  wherein the system is a dosage form as a monolithic tablet.  
     
     
         15 . The delivery system of  claim 11  wherein the system is a dosage form as a capsule.  
     
     
         16 . The delivery system of claim wherein the system is a dosage form as a wafer.  
     
     
         17 . The delivery system of  claim 11  wherein the system is an oral delivery system.  
     
     
         18 . The delivery system of  claim 11  wherein the system is an anal delivery system.  
     
     
         19 . The delivery system of  claim 11  wherein the system is a vaginal delivery system.  
     
     
         20 . The delivery system of  claim 11  wherein the biological component includes at least a bacteria.  
     
     
         21 . A delivery system for a biological component, the system comprising: 
 a delivery vehicle;    a release-modifying agent; and    a delivered component, the delivered component including the biological component.    
     
     
         22 . The delivery system of  claim 21  wherein the delivery vehicle is a hydrophilic agent, the hydrophilic agent selected from at least one of the group consisting of a starch, a polymer, a polysaccharide, a polypeptide, a cellulose derivative, an algae derivative and a gum.  
     
     
         23 . The delivery system of  claim 21  wherein the hydrophilic agent is selected from at least one of the group consisting of: 
 a) a starch selected from the group consisting of rice, corn and potato starch;    b) a gum selected from the group consisting of tragacanth gum, locust beam gum, acacia gum, guar gum, xanthan gum, ghatti gum and galactomannan gum;    c) an algae derivative selected from the group consisting of alginic acid, sodium alginate, agar, dextran and carageenan;    d) a polysaccharide selected from the group consisting of pectin and maltodextrin;    e) a cellulose derivative selected from the group consisting of methylcellulose, carboxymethylcellulose, sodium starch glycollate, sodium or calcium carboxymethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose, ethylhydroxy ethylcellulose, ethylmethylcellulose, hydroxyethylcellulose, cellulose acetate phthalate, hydroxypropyl cellulose and microcrystalline cellulose;    f) a desiccant selected from the group consisting of silica, aluminum silicate, magnesium silicate, aluminum magnesium silicate, sodium silicate and feldspar;    g) aluminum hydroxide;    h) a polypeptide selected from the group consisting of gelatin, collagen, casein and heterogeneous protein mixture; and    i) a polymer selected from the group consisting of acrylate, carboxypolymethylene, a polyalkylene glycol and polyvinylpyrrolidone.    
     
     
         24 . The delivery system of  claim 21  wherein the release-modifying agent is selected from at least one of the group consisting of: 
 a) an algae derivative selected from the group consisting of alginic acid, sodium alginate, agar, dextran and carageenan;    b) a polysaccharide selected from the group consisting of pectin and maltodextrin;    c) a polypeptide selected from the group consisting of gelatin, collagen, casein and heterogeneous protein mixture;    d) a polymer selected from the group consisting of acrylate, carboxypolymethylene, a polyalkylene glycol and polyvinylpyrrolidone;    e) a starch selected from the group consisting of rice, corn and potato starch;    f) a gum selected from the group consisting of tragacanth gum, locust beam gum, acacia gum, guar gum, xanthan gum, ghatti gum and galactomannan gum;    g) a cellulose derivative selected from the group consisting of methylcellulose, carboxymethylcellulose, sodium starch glycollate, sodium or calcium carboxymethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose, ethylcellulose, ethylhydroxy ethylcellulose, ethylmethylcellulose, hydroxyethylcellulose, cellulose acetate phthalate, hydroxypropyl ethylcellulose and microcrystalline cellulose;    h) aluminum hydroxide; and    i) a desiccant selected from the group consisting of silica, aluminum silicate, magnesium silicate, aluminum magnesium silicate, sodium silicate and feldspar.    
     
     
         25 . The delivery system of  claim 21  wherein the system is a dosage form as a monolithic tablet.  
     
     
         26 . The delivery system of  claim 21  wherein the system is a dosage form as a capsule.  
     
     
         27 . The delivery system of  claim 21  wherein the system is a dosage form as a wafer.  
     
     
         28 . The delivery system of  claim 21  wherein the system is an oral delivery system.  
     
     
         29 . The delivery system of  claim 21  wherein the delivery system is an anal delivery system.  
     
     
         30 . The delivery system of  claim 21  wherein the system is a vaginal delivery system.  
     
     
         31 . The delivery system of  claim 21  wherein the biological component includes at least a bacteria.  
     
     
         32 . A delivery system for a biological component wherein the system comprises: 
 a delivery vehicle, the delivery vehicle is a hydrophobic agent;    a release-modifying agent; and    a delivered component, the delivered component including the biological component.    
     
     
         33 . The delivery system of  claim 32  wherein the hydrophobic agent is a wax or an inert material.  
     
     
         34 . The delivery system of  claim 33  wherein the hydrophobic agent is a wax, the wax selected from at least one of the group consisting of bees wax, paraffin and camuba wax.  
     
     
         35 . The delivery system of  claim 33  wherein the hydrophobic agent is an inert material, the inert material is ethylcellulose.  
     
     
         36 . The delivery system of  claim 32  wherein the release-modifying agent is a pore-forming excipient selected from at least one of the group consisting of: 
 a) an algae derivative selected from the group consisting of alginic acid, sodium alginate, agar, dextran and carageenan;    b) a polysaccharide selected from the group consisting of pectin and maltodextrin;    c) a polypeptide selected from the group consisting of gelatin, collagen, casein and heterogeneous protein mixture;    d) a polymer selected from the group consisting of acrylate, carboxypolymethylene, polyalkylene glycol and polyvinylpyrrolidone;    e) a cellulose derivative selected from the group consisting of methylcellulose, carboxymethylcellulose, sodium starch glycollate, sodium or calcium carboxymethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose, ethylcellulose, ethylhydroxy ethylcellulose, ethylmethylcellulose, hydroxyethylcellulose, cellulose acetate phthalate, hydroxypropyl cellulose and microcrystalline cellulose; and    f) a salt selected from the group consisting of sodium, calcium, potassium and magnesium salts.    
     
     
         37 . The delivery system of  claim 32  wherein the delivery system is a dosage form as a monolithic tablet.  
     
     
         38 . The delivery system of  claim 32  wherein the delivery system is a dosage form as a capsule.  
     
     
         39 . The delivery system of  claim 32  wherein the delivery system is a dosage form as a wafer.  
     
     
         40 . The delivery system of  claim 32  wherein the delivery system is an oral delivery system.  
     
     
         41 . The delivery system of  claim 32  wherein the delivery system is an anal delivery system.  
     
     
         42 . The delivery system of  claim 32  wherein the delivery system is a vaginal delivery system.  
     
     
         43 . The delivery system of  claim 32  wherein the biological component includes at least a bacteria.  
     
     
         44 . A delivery system for a biological component wherein the system comprises: 
 a delivery vehicle, the delivery vehicle is a hydrophilic agent;    an electrolytic agent; and    a delivered component, the delivered component including the biological component.    
     
     
         45 . The delivery system of  claim 44  wherein the hydrophilic agent is selected from at least one of the group consisting of a starch, a polymer, a polysaccharide, a polypeptide, a cellulose derivative, an algae derivative and a gum.  
     
     
         46 . The delivery system of  claim 44  wherein the hydrophilic agent is selected from at least one of the group consisting of: 
 a) a starch selected from the group consisting of rice, corn and potato starch;    b) a gum selected from the group consisting of tragacanth gum, locust beam gum, acacia gum, guar gum, xanthan gum, ghatti gum and galactomannan gum;    c) an algae derivative selected from the group consisting of alginic acid, sodium alginate, agar, dextran and carageenan;    d) a polysaccharide selected from the group consisting of pectin and maltodextrin;    e) the cellulose derivative selected from the group consisting of methylcellulose, carboxymethylcellulose, sodium starch glycollate, sodium or calcium carboxymethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose, ethylhydroxy ethylcellulose, ethylmethylcellulose, hydroxyethylcellulose, cellulose acetate phthalate, hydroxypropyl cellulose and microcrystalline cellulose;    f) a desiccant selected from the group consisting of silica, aluminum silicate, magnesium silicate, aluminum magnesium silicate, sodium silicate and feldspar;    g) aluminum hydroxide;    h) a polypeptide selected from the group consisting of gelatin, collagen, casein and heterogeneous protein mixture; and    i) a polymer selected from the group consisting of acrylate, carboxypolymethylene, a polyalkylene glycol and polyvinylpyrrolidone.    
     
     
         47 . The delivery system of  claim 44  wherein the electrolytic agent is selected from at least one of the group consisting of: 
 a) a salt selected from the group consisting of sodium, calcium, potassium and magnesium salts;    b) an amino acid; and    c) an ionic compound.    
     
     
         48 . The delivery system of  claim 44  wherein the system is a dosage form as a monolithic tablet.  
     
     
         49 . The delivery system of  claim 44  wherein the system is a dosage form as a capsule.  
     
     
         50 . The delivery system of  claim 44  wherein the system is a dosage form as a wafer.  
     
     
         51 . The delivery system of  claim 44  wherein the system is an oral delivery system.  
     
     
         52 . The delivery system of  claim 44  wherein the system is an anal delivery system.  
     
     
         53 . The delivery system of  claim 44  wherein the system is a vaginal delivery system.  
     
     
         54 . The delivery system of  claim 44  wherein the biological component includes at least a bacteria.  
     
     
         55 . The delivery system of  claim 47  or  54  wherein the electrolytic agent is capable of inducing an internal pH of the dosage form that is physiologically acceptable to the reconstitution of the bacteria.  
     
     
         56 . A delivery system for a biological component wherein the system comprises: 
 a delivery vehicle, the delivery vehicle is a hydrophobic agent;    an electrolytic agent;    a release modifying agent; and    a delivered component, the delivered component including the biological component.    
     
     
         57 . The delivery system of  claim 56  wherein the hydrophobic agent is a wax or an inert material.  
     
     
         58 . The delivery system of  claim 57  wherein the hydrophobic agent is a wax, the wax selected from at least one of the group consisting of bees wax, paraffin and carnuba wax.  
     
     
         59 . The delivery system of  claim 57  wherein the hydrophobic agent is an inert material, the inert material is ethylcellulose.  
     
     
         60 . The delivery system of  claim 56  wherein the release-modifying agent is a pore-forming excipient selected from at least one of the group consisting of: 
 a) a polysaccharide selected from the group consisting of pectin and maltodextrin;    b) a cellulose derivative selected from the group consisting of methylcellulose, carboxymethylcellulose, sodium starch glycollate, sodium or calcium carboxymethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose, ethylcellulose, ethylhydroxy ethylcellulose, ethylmethylcellulose, hydroxyethylcellulose, cellulose acetate phthalate, hydroxypropyl cellulose and microcrystalline cellulose;    c) a polymer selected from the group consisting of acrylate, carboxypolymethylene, a polyalkylene glycol and polyvinylpyrrolidone;    d) a salt selected from the group consisting of sodium, calcium, potassium and magnesium salts;    e) an algae derivative selected from the group consisting of alginic acid, sodium alginate, agar, dextran and carageenan; and    f) a polypeptide selected from the group consisting of gelatin, collagen, casein and hetergeneous protein mixture.    
     
     
         61 . The delivery system of  claim 56  wherein the electrolytic agent is selected from at least one of the group consisting of: 
 a) a salt selected from the group consisting of sodium, calcium, potassium and magnesium salts;    b) an amino acid; and    c) an ionic compound.    
     
     
         62 . The delivery system of  claim 56  wherein the system is a dosage form as a monolithic tablet.  
     
     
         63 . The delivery system of  claim 56  wherein the system is a dosage form as a capsule.  
     
     
         64 . The delivery system of  claim 56  wherein the system is a dosage form as a wafer.  
     
     
         65 . The delivery system of  claim 56  wherein the system is an oral delivery system.  
     
     
         66 . The delivery system of  claim 56  wherein the system is an anal delivery system.  
     
     
         67 . The delivery system of  claim 56  wherein the system is a vaginal delivery system.  
     
     
         68 . The delivery system of  claim 56  wherein the biological component includes at least a bacteria.  
     
     
         69 . The delivery system of  claim 61  or  68  wherein the electrolytic agent is capable of inducing an internal pH of the dosage form that is physiologically acceptable to the reconstitution of the bacteria.  
     
     
         70 . A delivery system for a biological component wherein the system comprises: 
 a hydrophilic agent;    an electrolytic agent;    a release-modifying agent; and    a delivered component, the delivered component including the biological component.    
     
     
         71 . The delivery system of  claim 70  wherein the hydrophilic agent is selected from at least one of the group consisting of a starch, a polymer, a polysaccharide, a polypeptide, a cellulose derivative, an algae derivative and a gum..  
     
     
         72 . The delivery system of  claim 70  wherein the hydrophilic agent is selected from at least one of the group consisting of: 
 a) a starch selected from the group consisting of rice, corn and potato starch;    b) a gum selected from the group consisting of tragacanth gum, locust beam gum, acacia gum, guar gum, xanthan gum, ghatti gum and galactomannan gum;    c) an algae derivative selected from the group consisting of alginic acid, sodium alginate, agar, dextran and carageenan;    d) a polysaccharide selected from the group consisting of pectin and maltodextrin;    e) a cellulose derivative selected from the group consisting of methylcellulose, carboxymethylcellulose, sodium starch glycollate, sodium or calcium carboxymethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose, ethylhydroxy ethylcellulose, ethylmethylcellulose, hydroxyethylcellulose, cellulose acetate phthalate, hydroxypropyl cellulose and microcrystalline cellulose;    f) a desiccant selected from the group consisting of silica, aluminum silicate, magnesium silicate, aluminum magnesium silicate, sodium silicate and feldspar;    g) a polymer selected from the group consisting of acrylate, carboxypolymethylene, a polyalkylene glycol and polyvinylpyrrolidone;    h) a polypeptide selected from the group consisting of gelatin, collagen, casein and heterogeneous protein mixture; and    i) aluminum hydroxide.    
     
     
         73 . The delivery system of  claim 70  wherein the release-modifying agent is selected from at least one of the group consisting of: 
 a) an algae derivative selected from the group consisting of alginic acid, sodium alginate, agar, dextran and carageenan;    b) a polysaccharide selected from the group consisting of pectin and maltodextrin;    c) a polypeptide selected from the group consisting of gelatin, collagen, casein and heterogeneous protein mixture;    d) a polymer selected from the group consisting of acrylate, carboxypolymethylene, polyalkylene glycol and polyvinylpyrrolidone;    e) a gum selected from the group consisting of tragacanth gum, locust beam gum, acacia gum, guar gum, xanthan gum, ghatti gum and galactomannan gum;    f) a starch selected from the group consisting of rice, corn and starch;    g) a desiccant selected from the group consisting of silica, aluminum silicate, magnesium stearate, aluminum magnesium silicate, sodium silicate and feldspar;    h) aluminum hydroxide; and    i) a cellulose derivative selected from the group consisting of methylcellulose, carboxymethylcellulose, sodium starch glycollate, sodium or calcium carboxymethylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose, ethylcellulose, ethylhydroxy ethylcellulose, ethylmethylcellulose, hydroxyethylcellulose, cellulose acetate phthalate, hydroxypropyl cellulose and microcrystalline cellulose.    
     
     
         74 . The delivery system of  claim 70  wherein the electrolytic agent is selected from at least one of the group consisting of: 
 a) a salt selected from the group consisting of sodium, calcium, potassium and magnesium salts;    b) an amino acid; and    c) an ionic compound.    
     
     
         75 . The delivery system of  claim 70  wherein the system is a dosage form as a monolithic tablet.  
     
     
         76 . The delivery system of  claim 70  wherein the system is a dosage form as a capsule.  
     
     
         77 . The delivery system of  claim 70  wherein the system is a dosage form as a wafer.  
     
     
         78 . The delivery system of  claim 70  wherein the system is an oral delivery system.  
     
     
         79 . The delivery system of  claim 70  wherein the system is an anal delivery system.  
     
     
         80 . The delivery system of  claim 70  wherein the system is a vaginal delivery system.  
     
     
         81 . The delivery system of  claim 70  wherein the biological component includes at least a bacteria.  
     
     
         82 . The delivery system of  claim 74  or  81  wherein the electrolytic agent is capable of inducing an internal pH of the dosage form that is physiologically acceptable to the reconstitution of the bacteria.  
     
     
         83 . A gastric bypass delivery system comprising: 
 about 5% to 40% of hydrophilic agent by total weight;    about 5% to 40% of a release-modifying agent by total weight;    about 1 to 40% of an electrolytic agent by total weight;    and a biological component.    
     
     
         84 . The gastric bypass delivery system of  claim 83  wherein the hydrophilic agent is at least one of a cellulose derivative and a galactomannan gum.  
     
     
         85 . The gastric bypass delivery system of  claim 84  wherein the cellulose derivative is hydroxypropyl methylcellulose, hydroxypropyl cellulose, microccrystalline cellulose or polyethylene oxide.  
     
     
         86 . The gastric bypass delivery system of  claim 83  wherein the release-modifying agent is selected from at least one of the group consisting of a polysaccharide and a polypeptide.  
     
     
         87 . The gastric bypass delivery system of  claim 86  wherein the polysaccharide is a pectin or maltodextrin.  
     
     
         88 . The gastric bypass delivery system of  claim 86  wherein the polypeptide is a gelatin, collagen, casein or heterogenous protein mixture.  
     
     
         89 . The gastric bypass delivery system of  claim 83  wherein the electrolytic agent is selected from at least one of the group consisting of sodium carbonate, sodium biocarbonate, sodium phosphate and calcium carbonate.  
     
     
         90 . The gastric bypass delivery system of  claim 83  wherein the biological component is at least a bacteria.  
     
     
         91 . The gastric bypass delivery system of  claim 90  wherein the bacteria is a probiotic.  
     
     
         92 . The gastric bypass delivery system of  claim 83  wherein the system is an oral delivery system.  
     
     
         93 . The gastric bypass delivery system of  claim 83  wherein the system is a dosage form as a monolithic tablet.  
     
     
         94 . The gastric bypass delivery system of  claim 83  wherein the system is a dosage form as a capsule.  
     
     
         95 . The gastric bypass delivery system of  claim 83  wherein the system is a dosage form as a wafer.  
     
     
         96 . A dosage form is a blend of powders, the blend comprising: 
 about 5% to 40% of an hydrophilic agent by total weight;    about 5% to 40% of a release modifying agent by total weight;    about 1 to 40% of an electrolytic agent by total weight;    and a biological component.    
     
     
         97 . The dosage form of  claim 96  wherein the blend of powders is directly compressed into a monolithic tablet.  
     
     
         98 . The dosage form of  claim 96  wherein the blend of powders is encapsulated as a capsule.  
     
     
         99 . The dosage form of  claim 96  wherein the blend of powders is an oral delivery system.  
     
     
         100 . The dosage form of  claim 96  wherein the hydrophilic agent is selected from at least one of a cellulose derivative and galactomannan gum.  
     
     
         101 . The dosage form of  claim 100  wherein the cellulose derivative is hydroxypropyl methylcellulose, hydroxypropyl cellulose, microcrystalline cellulose or polyethylene oxide.  
     
     
         102 . The dosage form of  claim 96  wherein the release-modifying agent is selected from at least one of the group consisting of a polysaccharide and a polypeptide.  
     
     
         103 . The dosage form of  claim 102  wherein the polysaccharide is pectin or maltodextrin.  
     
     
         104 . The dosage form of  claim 102  wherein the polypeptide is selected from the group consisting of gelatin, collagen, casein and heterogeneous protein mixture.  
     
     
         105 . The dosage form of  claim 96  wherein the electrolytic agent is selected from at least one of the group consisting of sodium carbonate, sodium biocarbonate, sodium phosphate and calcium carbonate.  
     
     
         106 . The dosage form of  claim 96  wherein the biological component is at least a bacteria.  
     
     
         107 . The dosage form of  claim 106  wherein the bacteria is a probiotic.  
     
     
         108 . A method of manufacturing a dosage form comprising the steps of: 
 (a) desiccating an agent selected from the group consisting of a release modifying agent, an electrolytic agent and an hydrophilic agent;    (b) adding the agent to a biological component;    (c) compressing the agent and the biological component to form a monolithic tablet;    whereby a reduction in the available water content of the dosage form is produced.    
     
     
         109 . The method of  claim 108 , further comprising avoiding any moisture by adding the electrolytic agent.  
     
     
         110 . The method of  claim 108 , further comprising encapsulating the agent and the biological component to form a capsule.  
     
     
         111 . The method of  claim 108  wherein the biological component is at least a bacteria.  
     
     
         112 . The method of  claim 108 , further comprising adding a flow agent to improve manufacturability by decreasing the loss of viability of the biological components.  
     
     
         113 . The method of  claim 112 , wherein the flow agent is magnesium stearate or stearic acid.  
     
     
         114 . The method of  claim 108 , further comprising adding an inert filler to increase power flowability during the manufacturing of the dosage form.  
     
     
         115 . The method of  claim 114 , wherein the inert filler is micrystalline cellulose, di-calcium phosphate or carnauba wax.