# US 10,479,686 B2 · Sodium thiosulfate-containing pharmaceutical compositions

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- Number: US 10,479,686 B2
- Document ID: US10479686B2
- Status: Granted
- Kind: B2
- Application number: 15/916,950
- Filed: 2018-03-09
- Published: 2018-07-12
- Granted: 2019-11-19
- Earliest claimed: 2009-07-08
- Assignees: Hope Medical Enterprises, Inc.
- Applicants: Hope Medical Enterprises, Inc.
- Inventors: Craig Sherman; Catherine Marie Smith; Kevin Robert Wirtz; Erich Schulze
- Web page: https://patentgrep.com/patent/US10479686B2

## CPC

- C01B 17/64: Thiosulfates; Dithionites; Polythionates
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/404: Indoles, e.g. pindolol
- A61K 31/4418: having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 31/60: Salicylic acid; Derivatives thereof
- A61K 31/727: Heparin; Heparan
- A61K 33/00: Medicinal preparations containing inorganic active ingredients
- A61K 33/04: Sulfur, selenium or tellurium; Compounds thereof
- A61K 33/14: Alkali metal chlorides; Alkaline earth metal chlorides
- A61K 33/22: Boron compounds
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 3/14: for calcium homeostasis (vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04)
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/06: Antipsoriatics
- A61P 17/12: Keratolytics, e.g. wart or anti-corn preparations
- A61P 19/06: Antigout agents, e.g. antihyperuricemic or uricosuric agents
- A61P 27/16: Otologicals
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 39/02: Antidotes
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C01P 2006/80: Compositional purity
- Y10T 436/23: Carbon containing
- C01B: NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; {METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C}
- 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
- C01P: INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

Provided herein are pharmaceutically acceptable sodium thiosulfate and pharmaceutical compositions thereof. Also provided herein are methods for determining the total non-purgeable organic carbon in a sodium thiosulfate-containing sample. Further provided herein are methods for producing pharmaceutically acceptable sodium thiosulfate. Still further provided herein are methods of treatment comprising the administration of pharmaceutically acceptable sodium thiosulfate.

## Claims

### Claim 1

A pharmaceutical composition comprising sodium thiosulfate pentahydrate and one or more pharmaceutically acceptable carriers or excipients, wherein the sodium thiosulfate pentahydrate contains no greater than 8 ppm of non-purgeable organic carbon, contains no greater than 0.05 ppm of mercury, contains no greater than 2 ppm of aluminum, contains no greater than 0.003% by weight of selenium, contains no less than 98% by weight and no greater than about 102% by weight of sodium thiosulfate on an anhydrous basis measured by ion chromatography, has a water content between 32% and 37% by weight, has a heavy metal content of no greater than 10 ppm, contains no greater than 200 ppm of chloride, contains no greater than 0.001% by weight of sulfide, contains no greater than 0.002% by weight of iron, contains no greater than 0.01% by weight of calcium, contains no greater than 0.005% by weight of potassium, contains no greater than 0.1% of sulfite, contains no greater than 0.5% of sulfate, contains no greater than 3 ppm of arsenic, contains no greater than 0.001% by weight of lead, has total aerobic count of microbial load of no greater than 100 CFU/g, has total yeast and mold count of no greater than 20 CFU/g, contains no greater than 0.02 EU/mg of bacterial endotoxins, contains no greater than 0.002% by weight of nitrogen compounds, contains no greater than 0.005% by weight of insoluble matter, contains no greater than 0.01% by weight of residual anti-caking agent, and contains no greater than ICH Q3C (R3) limits of organic volatile impurities, wherein a 10% aqueous solution of the solid sodium thiosulfate pentahydrate at 25° C. is colorless and has a pH between 6.0 and 8.0, and wherein the solid sodium thiosulfate pentahydrate is odorless crystals,
wherein the pharmaceutical composition is formulated for parenteral administration; and
wherein the pharmaceutically acceptable carrier or excipient is an aqueous vehicle; a water-miscible vehicle; a non-aqueous vehicle; an antimicrobial agent or preservative against the growth of microorganisms; a stabilizer; a solubility enhancer; an isotonic agent; a buffering agent; an antioxidant; a local anesthetic; a suspending or dispersing agent; a wetting or emulsifying agent; a complexing agent; a sequestering or chelating agent; a cryoprotectant; a lyoprotectant; a thickening agent; a pH adjusting agent; or an inert gas.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the sodium thiosulfate pentahydrate has a positive identification test for sodium.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein the sodium thiosulfate pentahydrate has a positive identification test for thiosulfate.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition is formulated as a single dosage form.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable carrier or excipient is an aqueous vehicle.

### Claim 6 (depends on 5)

The pharmaceutical composition of claim 5, wherein the aqueous vehicle is water, saline, physiological saline, phosphate buffered saline, sodium chloride injection, Ringers injection, isotonic dextrose injection, sterile water injection, dextrose or lactated Ringers injection.

### Claim 7 (depends on 1)

The pharmaceutical composition of claim 1, wherein the non-aqueous vehicle is a fixed oil of vegetable origin, castor oil, corn oil, cottonseed oil, olive oil, peanut oil, peppermint oil, safflower oil, sesame oil, soybean oil, hydrogenated vegetable oil, hydrogenated soybean oil, medium-chain triglycerides of coconut oil, or palm seed oil.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1, wherein the water-miscible vehicle is ethanol, 1,3-butanediol, liquid polyethylene glycol, propylene glycol, glycerin, N-methyl-2-pyrrolidone, N,N-dimethylacetamide, or dimethyl sulfoxide.

### Claim 9 (depends on 8)

The pharmaceutical composition of claim 8, wherein the liquid polyethylene glycol is polyethylene glycol 300 or polyethylene glycol 400.

### Claim 10 (depends on 1)

The pharmaceutical composition of claim 1, wherein the antimicrobial agent or preservative against the growth of microorganisms is a phenol, a cresol, a mercurial, benzyl alcohol, chlorobutanol, methyl propyl p-hydroxybenzoate, propyl p-hydroxybenzoate, thimerosal, benzalkonium chloride, benzethonium chloride, a methyl-paraben, a propyl-paraben, or sorbic acid.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, wherein the isotonic agent is potassium chloride, mannitol, sodium chloride, dextran, glucose, glycerin, or dextrose.

### Claim 12 (depends on 1)

The pharmaceutical composition of claim 1, wherein the buffering agent is phosphate or citrate.

### Claim 13 (depends on 1)

The pharmaceutical composition of claim 1, wherein the antioxidant is bisulfite or sodium metabisulfite.

### Claim 14 (depends on 1)

The pharmaceutical composition of claim 1, wherein the local anesthetic is procaine hydrochloride.

### Claim 15 (depends on 1)

The pharmaceutical composition of claim 1, wherein the suspending or dispersing agent is sodium carboxymethylcelluose, hydroxypropyl methylcellulose, or polyvinylpyrrolidone.

### Claim 16 (depends on 1)

The pharmaceutical composition of claim 1, wherein the emulsifying agent is polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monooleate 80, or triethanolamine oleate.

### Claim 17 (depends on 1)

The pharmaceutical composition of claim 1, wherein the sequestering or chelating agent is EDTA.

### Claim 18 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pH adjusting agent is an acid or a base.

### Claim 19 (depends on 18)

The pharmaceutical composition of claim 18, wherein the acid is boric acid, hydrochloric acid, citric acid or lactic acid and the base is sodium hydroxide.

### Claim 20 (depends on 1)

The pharmaceutical composition of claim 1, wherein the complexing agent is a cyclodextrin.

### Claim 21 (depends on 20)

The pharmaceutical composition of claim 20, wherein the cyclodextrin is α-cyclodextrin, β-cyclodextrin, hydroxypropyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, and sulfobutylether 7-β-cyclodextrin.