# US 8,569,239 B2 · Glutathione based delivery system > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,569,239 B2 - Document ID: US8569239B2 - Status: Granted - Kind: B2 - Application number: 12/721,633 - Filed: 2010-03-11 - Published: 2010-07-01 - Granted: 2013-10-29 - Earliest claimed: 2005-12-19 - Assignees: Industrial Technology Research Institute - Applicants: Ae-June Wang; Chi-Heng Jian; Shyh-Dar Li; Yi-Fong Lin; Shih-Jr Liu - Inventors: Ae-June Wang; Chi-Heng Jian; Shyh-Dar Li; Yi-Fong Lin; Shih-Jr Liu - Web page: https://patentgrep.com/patent/US8569239B2 ## CPC - A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant - A61K 38/063: {Glutathione} - A61K 47/6911: {the form being a liposome} - A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/04: Centrally acting analgesics, e.g. opioids - A61P 39/00: General protective or antinoxious agents - Y10S 977/773: Nanoparticle, i.e. structure having three dimensions of 100 nm or less - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS ## Abstract A delivery system. The delivery system includes a carrier or an active compound and a glutathione or a glutathione derivative grafted thereon. The invention also provides a compound including a moiety comprising a vitamin E derivative or a phospholipid derivative, a polyethylene glycol (PEG) or a polyethylene glycol derivative bonded thereto, and a glutathione (GSH) or a glutathione derivative bonded to the polyethylene glycol or the polyethylene glycol derivative. ## Claims ### Claim 1 A method of traversing a blood brain barrier, comprising: administering a delivery system to a subject in need thereof, said delivery system comprising: a carrier which comprises glutathione, wherein said glutathione is covalently bound to polyethylene glycol, wherein the polyethylene glycol is covalently bound to vitamin E or a phospholipid, and wherein the vitamin E or phospholipid is intercalated into the carrier such that the glutathione is on an outside surface of the carrier. ### Claim 2 (depends on 1) The method of claim 1, wherein the carrier further comprises an active compound encapsulated thereinto, and wherein the active compound comprises small molecule compounds, peptides, proteins, DNA plasmids, oligonucleotides, or gene fragments. ### Claim 3 (depends on 1) The method of claim 1, wherein the carrier is a nanoparticle, a polymeric nanoparticle, a solid liquid nanoparticle, a polymeric micelle, a liposome, a microemulsion, or a liquid-based nanoparticle. ### Claim 4 (depends on 3) The method of claim 3, wherein the liposome comprises at least one of lecithin and hydrogenated lecithin, and wherein the liposome further optionally comprises cholesterol, water-soluble vitamin E, or octadecyl amine. ### Claim 5 (depends on 1) The method of claim 1, wherein the phospholipid has formula (I): R1-A1- (I) wherein A1 is sphingosine and R1 comprises octanoyl or palmitoyl. ### Claim 6 (depends on 1) The method of claim 1, wherein the phospholipid has formula (II): wherein A2 is phosphoethanoamine and R2 comprises myristoyl, palmitoyl, stearoyl, or oleoyl. ### Claim 7 (depends on 1) The method of claim 1, wherein the polyethylene glycol has a molecular weight of about 300-10000 and is covalently bound to vitamin E. ### Claim 8 (depends on 5) The method of claim 5, wherein the polyethylene glycol has a molecular weight of about 750-5000 and is covalently bound to the phospholipid of formula (I). ### Claim 9 (depends on 6) The method of claim 6, wherein the polyethylene glycol has a molecular weight of about 350-5000 and is covalently bound to the phospholipid of formula (II). ### Claim 10 (depends on 1) The method of claim 1, wherein the polyethylene glycol has a polymerization number (n) of about 6-210. ### Claim 11 A method of traversing a blood brain barrier, comprising: administering a delivery system to a subject in need thereof, said delivery system comprising: a carrier; and glutathione, wherein the carrier is a nanoparticle, a polymeric nanoparticle, a solid liquid nanoparticle, a polymeric micelle, a liposome, a microemulsion, or a liquid-based nanoparticle, and wherein said glutathione is covalently bound to polyethylene glycol, wherein the polyethylene glycol is covalently bound to vitamin E or a phospholipid, and wherein the vitamin E or phospholipid is intercalated into the carrier, such that the glutathione is on an outside surface of the carrier. ### Claim 12 A method of traversing a blood brain barrier, comprising: administering a delivery system to a subject in need thereof, said delivery system comprising: a carrier comprising a glutathione derivative, wherein the carrier is selected from group consisting of: a nanoparticle, a polymeric nanoparticle, a solid liquid nanoparticle, a polymeric micelle, a liposome, a microemulsion, and a liquid-based nanoparticle, wherein said glutathione derivative is covalently bound to a polyethylene glycol derivative which is itself covalently bound to a vitamin E derivative or a phospholipid, wherein said polyethylene glycol derivative is selected from the group consisting of: polyethylene glycol, a polyethylene glycol comprising carboxylic acid, a polyethylene glycol comprising maleimide, a polyethylene glycol comprising an amide, and a polyethylene glycol comprising biotin, wherein said vitamin E derivative is selected from the group consisting of vitamin E, α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, α-tocopherol succinate, β-tocopherol succinate, γ-tocopherol succinate, δ-tocopherol succinate, α-tocotrienol succinate, β-tocotrienol succinate, γ-tocotrienol succinate, δ-tocotrienol succinate, α-tocopherol acetate, β-tocopherol acetate, γ-tocopherol acetate, δ-tocopherol acetate, α-tocotrienol acetate, β-tocotrienol acetate, γ-tocotrienol acetate, δ-tocotrienol acetate, α-tocopherol nicotinate, β-tocopherol nicotinate, γ-tocopherol nicotinate, δ-tocopherol nicotinate, α-tocotrienol nicotinate, β-tocotrienol nicotinate, γ-tocotrienol nicotinate, δ-tocotrienol nicotinate, α-tocopherol phosphate, β-tocopherol phosphate, γ-tocopherol phosphate, δ-tocopherol phosphate, α-tocotrienol phosphate, β-tocotrienol phosphate, γ-tocotrienol phosphate, and δ-tocotrienol phosphate, and wherein the phospholipid has the structure of formula (II): wherein A2 is phosphoethanoamine and R2 is selected from the group consisting of: myristoyl, palmitoyl, stearoyl, and oleoyl, wherein the glutathione is on an outside surface of the carrier.