Method for reducing damage caused by free radicals
Inventors
Chen, Chia-Hung • Wang, Chau-Hui • Lin, John-Son • Chiu, Tieh-Hsiung • Chen, Jing-Yi • Liao, Pi-Hung • Su, Chia-Chi • Liao, Wei-Chuan
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9795677-B2
Publication Date
2017-10-24
Expiration Date
Abstract
The present invention features a method for reducing the damage caused by free radicals, the method comprises administering a pharmaceutical composition that comprises at least a metal or its ions, at least a drug or an antioxidant that is carrier-protected/modified, and a drug carrier to a subject. Said carrier helps to preserve the anti-oxidative activity, and hence, prevents the decrease of the effect of the antioxidant against free radicals produced in the environment or body fluids and prolongs protection, and be used for reducing damage caused by radiation and adverse effects induced by chemotherapeutic drugs.
Core Innovation
The invention relates to a method for reducing the damage caused by free radicals by administering a pharmaceutical composition to a subject. The pharmaceutical composition consists of iron ion, amifostine, and poly(ethylene glycol)-b-poly(glutamic acid) (PEG-b-PGA), and the center of the pharmaceutical composition consists of the iron ion and is enclosed by amifostine and an outer layer made of poly(ethyleneglycol)-b-poly(glutamic acid).
In the disclosed specific embodiment, an iron-center formulation is provided in which an iron compound and amifostine are associated with PEG-b-PGA in a micelle-like structure formed by self-assembly and coordinate bonding. The partial content states an iron compound of FeCl2·4H2O together with PEG-b-PGA and amifostine, with the formulation weight ratio PEG-b-PGA:FeCl2·4H2O:amifostine of 4:1:1.
The disclosure further asserts that the iron/PEG-b-PGA/amifostine structure provides prolonged activity through delayed release and altered in vivo distribution. The partial content reports in vitro Comet Assay results showing reduced DNA tail damage after UV exposure when cells are treated with the FePA formulation versus controls, and in vivo radiation protection outcomes in mice including improved WBC counts, survival, and hematopoietic protection relative to radiation control and comparison to standard amifostine dosing.
Claims Coverage
The independent claim is clm-00001. It defines one inventive feature: administering a specific iron ion/amifostine/PEG-b-PGA pharmaceutical composition with an iron-ion-centered structure enclosed by amifostine and an outer PEG-b-PGA layer.
Iron-ion-centered PEG-b-PGA/amifostine micelle pharmaceutical composition
A pharmaceutical composition consisting of iron ion, amifostine, and poly(ethylene glycol)-b-poly(glutamic acid) (PEG-b-PGA), wherein the center consists of the iron ion and is enclosed by amifostine and an outer layer made of poly(ethyleneglycol)-b-poly(glutamic acid).
Method of reducing damage caused by free radicals by administration
A method for reducing the damage caused by free radicals, comprising administering the pharmaceutical composition to a subject.
Free-radical damage contexts include radiation therapy and ultraviolet light
The subject whose cells, tissues, and organs have free-radical damage caused by ultraviolet light, radiation therapy, chemotherapeutic drugs, or electromagnetic effects.
Chemotherapeutic drug example as cisplatin
The chemotherapeutic drugs comprise cisplatin.
Intravenous administration
The pharmaceutical composition is administered by intravenous injection into the subject.
Amifostine dosage for a human based on body weight
Amifostine is administered at about 30 mg for a 60 kg body-weight human.
Formulation weight ratio constraint PEG-b-PGA:FeCl2·4H2O:amifostine
The pharmaceutical composition has a formulation weight ratio PEG-b-PGA:FeCl2·4H2O:amifostine of 4:1:1.
Overall, the claim set centers on administering a pharmaceutical composition where iron ion forms the core, amifostine encloses the iron ion, and an outer PEG-b-PGA layer is present, applied as a method for reducing free-radical damage with optional refinements including specific free-radical damage sources, cisplatin, intravenous injection, and specified dosage/weight-ratio constraints.
Stated Advantages
Reduces damage caused by free radicals.
Reduced DNA tail damage after UV exposure compared with controls.
Improved WBC counts and survival in mice relative to radiation control.
Hematopoietic protection and prolonged activity via delayed release and altered in vivo distribution.
Provides radiation protection outcomes in mice and is compared with standard amifostine dosing.
Documented Applications
Reducing free-radical damage in subjects, including damage caused by ultraviolet light, radiation therapy, chemotherapeutic drugs, or electromagnetic effects.
Reducing radiation toxicity/chemotherapy adverse effects in the context of radiation protection, with cisplatin identified as an example chemotherapeutic drug.
In vitro reduction of DNA tail damage after UV exposure using Comet Assay.
In vivo radiation protection in mice, including improved WBC counts, survival, and hematopoietic protection.
Interested in licensing this patent?