CA2509365A1 - Compositions and methods of delivery of pharmacological agents - Google Patents
Compositions and methods of delivery of pharmacological agents Download PDFInfo
- Publication number
- CA2509365A1 CA2509365A1 CA 2509365 CA2509365A CA2509365A1 CA 2509365 A1 CA2509365 A1 CA 2509365A1 CA 2509365 CA2509365 CA 2509365 CA 2509365 A CA2509365 A CA 2509365A CA 2509365 A1 CA2509365 A1 CA 2509365A1
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- CA
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- Prior art keywords
- pharmaceutical composition
- pharmaceutical
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- albumin
- administration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract 73
- 239000000203 mixture Substances 0.000 title 1
- 239000002831 pharmacologic agent Substances 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 105
- 239000008177 pharmaceutical agent Substances 0.000 claims abstract 54
- 239000003937 drug carrier Substances 0.000 claims abstract 22
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 claims abstract 10
- 229960000958 deferoxamine Drugs 0.000 claims abstract 10
- 102000004169 proteins and genes Human genes 0.000 claims abstract 9
- 108090000623 proteins and genes Proteins 0.000 claims abstract 9
- 230000000694 effects Effects 0.000 claims abstract 8
- -1 for example Proteins 0.000 claims abstract 6
- 230000002401 inhibitory effect Effects 0.000 claims abstract 5
- 230000000813 microbial effect Effects 0.000 claims abstract 4
- 230000003647 oxidation Effects 0.000 claims abstract 4
- 238000007254 oxidation reaction Methods 0.000 claims abstract 4
- 230000002708 enhancing effect Effects 0.000 claims abstract 3
- 102000009027 Albumins Human genes 0.000 claims 35
- 108010088751 Albumins Proteins 0.000 claims 35
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 claims 15
- 229960004134 propofol Drugs 0.000 claims 15
- 229960001425 deferoxamine mesylate Drugs 0.000 claims 10
- IDDIJAWJANBQLJ-UHFFFAOYSA-N desferrioxamine B mesylate Chemical compound [H+].CS([O-])(=O)=O.CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN IDDIJAWJANBQLJ-UHFFFAOYSA-N 0.000 claims 10
- 239000007788 liquid Substances 0.000 claims 8
- 208000024172 Cardiovascular disease Diseases 0.000 claims 7
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 6
- 210000004027 cell Anatomy 0.000 claims 6
- 239000003795 chemical substances by application Substances 0.000 claims 6
- ITPDYQOUSLNIHG-UHFFFAOYSA-N Amiodarone hydrochloride Chemical compound [Cl-].CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCC[NH+](CC)CC)C(I)=C1 ITPDYQOUSLNIHG-UHFFFAOYSA-N 0.000 claims 5
- 229930183010 Amphotericin Natural products 0.000 claims 5
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 claims 5
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims 5
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims 5
- 108010036949 Cyclosporine Proteins 0.000 claims 5
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims 5
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims 5
- 229930012538 Paclitaxel Natural products 0.000 claims 5
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims 5
- 229940123237 Taxane Drugs 0.000 claims 5
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 claims 5
- 102000055135 Vasoactive Intestinal Peptide Human genes 0.000 claims 5
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 claims 5
- 239000002253 acid Substances 0.000 claims 5
- 150000007513 acids Chemical class 0.000 claims 5
- 229960005260 amiodarone Drugs 0.000 claims 5
- 229940009444 amphotericin Drugs 0.000 claims 5
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims 5
- 229940035676 analgesics Drugs 0.000 claims 5
- 229940035674 anesthetics Drugs 0.000 claims 5
- 239000000730 antalgic agent Substances 0.000 claims 5
- 239000003242 anti bacterial agent Substances 0.000 claims 5
- 230000001088 anti-asthma Effects 0.000 claims 5
- 239000002260 anti-inflammatory agent Substances 0.000 claims 5
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 5
- 229940044684 anti-microtubule agent Drugs 0.000 claims 5
- 239000003416 antiarrhythmic agent Substances 0.000 claims 5
- 229940124346 antiarthritic agent Drugs 0.000 claims 5
- 239000000924 antiasthmatic agent Substances 0.000 claims 5
- 229940088710 antibiotic agent Drugs 0.000 claims 5
- 239000003429 antifungal agent Substances 0.000 claims 5
- 229940121375 antifungal agent Drugs 0.000 claims 5
- 239000002220 antihypertensive agent Substances 0.000 claims 5
- 229940030600 antihypertensive agent Drugs 0.000 claims 5
- 239000002246 antineoplastic agent Substances 0.000 claims 5
- 239000003435 antirheumatic agent Substances 0.000 claims 5
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims 5
- 229940127093 camptothecin Drugs 0.000 claims 5
- 229960001265 ciclosporin Drugs 0.000 claims 5
- 239000003246 corticosteroid Substances 0.000 claims 5
- 229960001334 corticosteroids Drugs 0.000 claims 5
- 229930182912 cyclosporin Natural products 0.000 claims 5
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims 5
- 229960003668 docetaxel Drugs 0.000 claims 5
- 229930013356 epothilone Natural products 0.000 claims 5
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 claims 5
- 239000003193 general anesthetic agent Substances 0.000 claims 5
- 229940088597 hormone Drugs 0.000 claims 5
- 239000005556 hormone Substances 0.000 claims 5
- 229940125721 immunosuppressive agent Drugs 0.000 claims 5
- 239000003018 immunosuppressive agent Substances 0.000 claims 5
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 claims 5
- 229960003987 melatonin Drugs 0.000 claims 5
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims 5
- 229960001592 paclitaxel Drugs 0.000 claims 5
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims 5
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims 5
- 229960002930 sirolimus Drugs 0.000 claims 5
- 229960001967 tacrolimus Drugs 0.000 claims 5
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 claims 5
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 5
- 239000005495 thyroid hormone Substances 0.000 claims 5
- 229940036555 thyroid hormone Drugs 0.000 claims 5
- 229940035722 triiodothyronine Drugs 0.000 claims 5
- 239000002550 vasoactive agent Substances 0.000 claims 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 4
- 238000001727 in vivo Methods 0.000 claims 4
- 150000007523 nucleic acids Chemical group 0.000 claims 4
- 238000000338 in vitro Methods 0.000 claims 3
- 238000007918 intramuscular administration Methods 0.000 claims 3
- 238000007913 intrathecal administration Methods 0.000 claims 3
- 238000001990 intravenous administration Methods 0.000 claims 3
- 238000007920 subcutaneous administration Methods 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 206010003246 arthritis Diseases 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 206010065553 Bone marrow failure Diseases 0.000 claims 1
- 108010001857 Cell Surface Receptors Proteins 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 206010029350 Neurotoxicity Diseases 0.000 claims 1
- 208000002193 Pain Diseases 0.000 claims 1
- 206010040880 Skin irritation Diseases 0.000 claims 1
- 206010044221 Toxic encephalopathy Diseases 0.000 claims 1
- 208000026935 allergic disease Diseases 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 210000002889 endothelial cell Anatomy 0.000 claims 1
- 230000009610 hypersensitivity Effects 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 238000001361 intraarterial administration Methods 0.000 claims 1
- 230000007794 irritation Effects 0.000 claims 1
- 102000006240 membrane receptors Human genes 0.000 claims 1
- 230000007135 neurotoxicity Effects 0.000 claims 1
- 231100000228 neurotoxicity Toxicity 0.000 claims 1
- 239000007764 o/w emulsion Substances 0.000 claims 1
- 208000001297 phlebitis Diseases 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 230000036556 skin irritation Effects 0.000 claims 1
- 231100000475 skin irritation Toxicity 0.000 claims 1
- 102000008100 Human Serum Albumin Human genes 0.000 abstract 2
- 108091006905 Human Serum Albumin Proteins 0.000 abstract 2
Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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- A61K31/16—Amides, e.g. hydroxamic acids
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- A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
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- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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Abstract
The present invention relates to a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, which carrier comprises a protein, for example, human serum albumin and/or deferoxamine. The human serum albumin is present in an amount effective to reduce one or more side effects associated with administration of the pharmaceutical composition. The invention also provides methods for reducing one or more side effects of administration of the pharmaceutical composition, methods for inhibiting microbial growth and oxidation in the pharmaceutical composition, and methods for enhancing transport and binding of a pharmaceutical agent to a cell.
Claims (93)
1. A pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises albumin in an amount effective to reduce one or more side effects of administration of the pharmaceutical composition into a human, and wherein the pharmaceutically acceptable,carrier comprises deferoxamine in an amount effective to inhibit microbial growth in the pharmaceutical composition.
2. The pharmaceutical composition of claim 1, wherein the pharmaceutical agent is selected from the group consisting of anticancer agents, anesthetics, antimicrotubule agents, agents to treat cardiovascular disorders, antihypertensives, anti-inflammatory agents, anti-arthritic agents, antiasthmatics, analgesics, vasoactive agents, immunosuppressive agents, antifungal agents, antiarrhythmic agents, antibiotics, and hormones.
3. The pharmaceutical composition of claim 2, wherein the pharmaceutical agent is selected from the group consisting of paclitaxel, docetaxel, taxanes, camptothecin, propofol, amiodarone, cyclosporine, rapamycin, amphotericin, liothyronine, epothilones, colchicines, thyroid hormones, vasoactive intestinal peptide, corticosteroids, melatonin, tacrolimus, mycophenolic acids, and derivatives thereof.
4. The pharmaceutical composition of claim 3, wherein the pharmaceutical agent is propofol.
5. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a liquid and comprises from about 0.1% to about 25% by weight of albumin.
6. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition comprises about 0.5% to about 5% by weight of albumin.
7. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition is dehydrated.
8. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition is lyophilized.
9. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises a mesylate salt of deferoxamine.
10. The pharmaceutical composition of claim 9, wherein the pharmaceutical composition is a liquid and comprises from about 0.0001 % to about 0.5% by weight of deferoxamine mesylate.
11. The pharmaceutical composition of claim 10, wherein the pharmaceutical composition comprises about 0.1% by weight of deferoxamine mesylate.
12. The pharmaceutical composition of claim 10, wherein the pharmaceutical composition is dehydrated.
13. The pharmaceutical composition of claim 12, wherein the pharmaceutical composition is lyophilized.
14. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is an oil-in-water emulsion.
15. The pharmaceutical composition of claim 5, wherein the pharmaceutical agent is propofol.
16. The pharmaceutical composition of claim 10, wherein the pharmaceutical agent is propofol.
17. The pharmaceutical composition of claim 9, wherein the pharmaceutical agent is propofol, the propofol is present in an amount from about 0.1% to about 5% by weight, the albumin is present in an amount from about 0.1% to about 25% by weight, and the deferoxamine mesylate is present in an amount from about 0.0001% to about 0.5% by weight.
18. A pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises albumin in an amount effective to reduce one or more side effects of administration of the pharmaceutical composition into a human, and wherein the pharmaceutically acceptable carrier comprises deferoxamine in an amount effective to inhibit oxidation in the pharmaceutical composition.
19. A method for reducing one or more side effects associated with administration of a pharmaceutical composition to a human, which method comprises administering to a human a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises albumin and deferoxamine.
20. The method of claim 19, wherein the pharmaceutical agent is selected from the group consisting of anticancer agents, anesthetics, antimicrotubule agents, agents to treat cardiovascular disorders, antihypertensives, anti-inflammatory agents, anti-arthritic agents, antiasthmatics, analgesics, vasoactive agents, immunosuppressive agents, antifungal agents, antiarrhythmic agents, antibiotics, and hormones.
21. The method of claim 20, wherein the pharmaceutical agent is selected from the group consisting of paclitaxel, docetaxel, taxanes, camptothecin, propofol, amiodarone, cyclosporine, rapamycin, amphotericin, liothyronine, epothilones, colchicines, thyroid hormones, vasoactive intestinal peptide, corticosteroids, melatonin, tacrolimus, mycophenolic acids, and derivatives thereof.
22. The method of claim 21, wherein the pharmaceutical agent is propofol.
23. The method of claim 19, wherein the pharmaceutical composition is a liquid and comprises from about 0.1% to about 25% by weight of albumin.
24. The method of claim 23, wherein the pharmaceutical composition comprises about 0.5% to about 5% by weight of albumin.
25. The method of claim 23, wherein the pharmaceutical composition is dehydrated.
26. The method of claim 25, wherein the pharmaceutical composition is lyophilized.
27. The method of claim 23, wherein the pharmaceutical agent is propofol.
28. The method of claim 19, wherein the pharmaceutical composition comprises a mesylate salt of deferoxamine.
29. The method of claim 28, wherein the pharmaceutical composition is a liquid and comprises from about 0.0001% to about 0.5% by weight of deferoxamine mesylate.
30. The method of claim 29, wherein the pharmaceutical composition comprises about 0.1% by weight of deferoxamine mesylate.
31. The method of claim 29, wherein the pharmaceutical composition is dehydrated.
32. The method of claim 31, wherein the pharmaceutical composition is lyophilized.
33. The method of claim 29, wherein the pharmaceutical agent is propofol.
34. The. method of claim 28, wherein the pharmaceutical agent is propofol, the propofol is present in an amount from about 0.1% to about 5% by weight, the albumin is present in an amount from about 0.1% to about 25% by weight, and the deferoxamine mesylate is present in an amount from about 0.0001% to about 0.5% by weight.
35. The method of claim 19, wherein the pharmaceutical composition is administered to the human via intravenous administration, intra-arterial administration, intrapulmonary administration, oral administration, inhalation, intra-tracheal administration, intravesicular administration, intramuscular administration, subcutaneous administration, intraocular administration, intrathecal administration, or transdermal administration.
36. The method of claim 19, wherein the one or more side effects are selected from the group consisting of myelosuppression, neurotoxicity, hypersensitivity, venous irritation, inflammation, phlebitis, pain, skin irritation, and combinations thereof.
37. A method for inhibiting microbial growth in a pharmaceutical composition, which method comprises preparing a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises deferoxamine in an amount effective for inhibiting microbial growth in the pharmaceutical composition.
38. The method of claim 37, wherein the pharmaceutical composition comprises a mesylate salt of deferoxamine.
39. The method of claim 38, wherein the pharmaceutical composition is a liquid and comprises from about 0.0001 % to about 0.5% by weight of deferoxamine mesylate.
40. The method of claim 39, wherein the pharmaceutical composition comprises about 0.1% by weight of deferoxamine mesylate.
41. The method of claim 39, wherein the pharmaceutical composition is dehydrated.
42. The method of claim 41, wherein the pharmaceutical composition is lyophilized.
43. The method of claim 37, wherein the pharmaceutical composition further comprises albumin.
44. A method for inhibiting oxidation of a pharmaceutical composition, which method comprises preparing a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises deferoxamine in an amount effective for inhibiting oxidation of the pharmaceutical composition.
45. The method of claim 44, wherein the pharmaceutical composition comprises a mesylate salt of deferoxamine.
46. The method of claim 45, wherein the pharmaceutical composition is a liquid and comprises from about 0.0001% to about 0.5% by weight of deferoxamine mesylate.
47. The method of claim 46, wherein the pharmaceutical composition comprises about 0.1% by weight of deferoxamine mesylate.
48. The method of claim 46, wherein the pharmaceutical composition is dehydrated.
49. The method of claim 48, wherein the pharmaceutical composition is lyophilized.
50. The method of claim 44, wherein the pharmaceutical composition further comprises albumin.
51. A method for enhancing transport of a pharmaceutical agent to the site of an infirmity, which method comprises administering to a human a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises albumin, and wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 18:1 or less.
52. The method of claim 51, wherein the pharmaceutical agent is selected from the group consisting of anticancer agents, anesthetics, antimicrotubule agents, agents to treat cardiovascular disorders, antihypertensives, anti-inflammatory agents, anti-arthritic agents, antiasthmatics, analgesics, vasoactive agents immunosuppressive agents, antifungal agents, antiarrhythmic agents, antibiotics, and hormones.
53. The method of claim 52, wherein the pharmaceutical agent is selected from the group consisting of paclitaxel, docetaxel, taxanes, camptothecin, propofol, amiodarone, cyclosporine, rapamycin, amphotericin, liothyronine, epothilones, colchicines, thyroid hormones, vasoactive intestinal peptide, corticosteroids, melatonin, tacrolimus, mycophenolic acids, and derivatives thereof.
54. The method of claim 51, wherein the pharmaceutical agent is a nucleic acid sequence.
55. The method of claim 54, wherein the nucleic acid sequence is a DNA
sequence
sequence
56. The method of claim 51, wherein the infirmity is selected from the group consisting of cancer, arthritis, and cardiovascular disease.
57. The method of claim 51, wherein the pharmaceutical composition is a liquid and comprises from about 0.1% to about 25% by weight of albumin.
58. The method of claim 57, wherein the pharmaceutical composition comprises about 0.5% to about 5% by weight of albumin.
59. The method of claim 57, wherein the pharmaceutical composition is dehydrated.
60. The method of claim 59, wherein the pharmaceutical composition is lyophilized.
61. The method of claim 51, wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 12:1 or less.
62. The method of claim 51, wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 9:1 or less.
63. The method of claim 51, wherein the pharmaceutical composition is administered to the human via intravenous administration, infra-arterial administration, intrapulmonary administration, oral administration, inhalation, infra-tracheal administration, intravesicular administration, intramuscular administration, subcutaneous administration, intraocular administration, intrathecal administration, or transdermal administration.
64. A method for enhancing binding of a pharmaceutical agent to a cell in vitro or in vivo, which method comprises administering to said cell in vitro or in vivo, a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises albumin, and wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 18:1 or less.
65. The method of claim 64, wherein the pharmaceutical agent is selected from the group consisting of anticancer agents, anesthetics, antimicrotubule agents, agents to treat cardiovascular disorders, antihypertensives, anti-inflammatory agents, anti-arthritic agents, antiasthmatics, analgesics, vasoactive agents, immunosuppressive agents, antifungal agents, antiarrhythmic agents, antibiotics, and hormones.
66. The method of claim 65, wherein the pharmaceutical agent is selected from the group consisting of paclitaxel, docetaxel, taxanes, camptothecin, propofol, amiodarone, cyclosporine, rapamycin, amphotericin, liothyronine, epothilones, colchicines, thyroid hormones, vasoactive intestinal peptide, corticosteroids, melatonin, tacrolimus, mycophenolic acids, and derivatives thereof.
67. The method of claim 64, wherein the pharmaceutical agent is a nucleic acid sequence.
68. The method of claim 67, wherein the nucleic acid sequence is a DNA
sequence
sequence
69. The method of claim 64, wherein the cell is an endothelial cell.
70. The method of claim 64, wherein the pharmaceutical composition is a liquid and comprises from about 0.1% to about 25% by weight of albumin.
71. The method of claim 70, wherein the pharmaceutical composition comprises about 0.5% to about 5% by weight of albumin.
72. The method of claim 70, wherein the pharmaceutical composition is dehydrated.
73. The method of claim 72, wherein the pharmaceutical composition is lyophilized.
74. The method of claim 64, wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 12:1 or less.
75. The method of claim 64, wherein the ratio of albumin to pharmaceutical gent in the pharmaceutical composition is about 9:1 or less
76. The method of claim 64, wherein the pharmaceutical composition is administered to the cell in vivo via intravenous administration, infra-arterial administration, intrapulmonary administration, oral administration, inhalation, infra-tracheal administration, intravesicular administration, intramuscular administration, subcutaneous administration, intraocular administration, intrathecal administration, or transdermal administration.
77. A pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises albumin in an amount effective to reduce one or more side.effects of administration of the pharmaceutical composition into a human, and wherein the ratio of albumin to pharmaceutical agent is about 18:1 or less.
78. The pharmaceutical composition of claim 77, wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 12:1 or less.
79. The pharmaceutical composition of claim 77, wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 9:1 or less.
80. A pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises albumin in an amount effective to increase transport of the drug to the site of infirmity in a human, and wherein the ratio of albumin to pharmaceutical agent is about 18:1 or less.
81. The pharmaceutical composition of claim 80, wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 12:1 or less.
82. The pharmaceutical composition of claim 80, wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 9:1 or less.
83. The pharmaceutical composition of claim 80, wherein the infirmity is selected from the group consisting of cancer, arthritis, and cardiovascular disease.
84. The pharmaceutical composition of claim 1, wherein the ratio of albumin to pharmaceutical agent is about 18:1 or less.
85. A method for increasing the transport of a pharmaceutical agent to a cell in vitro or in vivo by combining said agent with a protein, wherein said protein binds a specific cell-surface receptor on said cell, wherein said binding of the protein-pharmaceutical agent combination with the said receptor causes the transport to occur, and wherein the ratio of protein to pharmaceutical agent is about 18:1 or less.
86. The method of claim 85, wherein the protein is albumin.
87. The method of claim 85, wherein the pharmaceutical agent is selected from the group consisting of anticancer agents, anesthetics, antimicrotubule agents, agents to treat cardiovascular disorders, antihypertensives, anti-inflammatory agents, anti-arthritic agents, antiasthmatics, analgesics, vasoactive agents, immunosuppressive agents, antifungal agents, antiarrhythmic agents, antibiotics, and hormones.
88. The method of claim 87, wherein the pharmaceutical agent is selected from the group consisting of paclitaxel, docetaxel, taxanes, camptothecin, propofol, amiodarone, cyclosporine, rapamycin, amphotericin, liothyronine, epothilones, colchicines, thyroid hormones, vasoactive intestinal peptide, corticosteroids, melatonin, tacrolimus, mycophenolic acids, and derivatives thereof.
89. The method of claim 85, wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 12:1 or less.
90. The method of claim 85, wherein the ratio of albumin to pharmaceutical agent in the pharmaceutical composition is about 9:1 or less.
91. A pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises a protein in an amount effective to reduce one or more side effects of administration of the pharmaceutical composition into a human, and wherein the ratio of protein to pharmaceutical agent is about 18:1 or less.
92. The pharmaceutical composition of claim 91, wherein the ratio of protein to pharmaceutical agent in the pharmaceutical composition is about 12:1 or less.
93. The pharmaceutical composition of claim 91, wherein the ratio of protein to pharmaceutical agent in the pharmaceutical composition is about 9:1 or less.
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2014
- 2014-04-10 RU RU2014114221/15A patent/RU2014114221A/en not_active Application Discontinuation
- 2014-08-18 JP JP2014165626A patent/JP2014218517A/en not_active Withdrawn
-
2015
- 2015-02-19 US US14/626,678 patent/US20150165047A1/en not_active Abandoned
- 2015-05-25 JP JP2015105380A patent/JP2015147814A/en not_active Withdrawn
- 2015-11-03 HK HK15110831.5A patent/HK1210032A1/en unknown
-
2017
- 2017-01-30 JP JP2017013932A patent/JP2017095513A/en not_active Withdrawn
- 2017-09-07 JP JP2017171875A patent/JP2017226694A/en active Pending
-
2018
- 2018-07-18 JP JP2018134918A patent/JP2018184434A/en active Pending
- 2018-08-29 CY CY181100901T patent/CY1120625T1/en unknown
-
2019
- 2019-10-24 JP JP2019193548A patent/JP2020011999A/en active Pending
- 2019-10-24 JP JP2019193549A patent/JP2020023564A/en active Pending
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