# US 11,111,218 B2 · Crystalline form of 5-amino-2,3-dihydrophthalazine-1,4-dione

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- Number: US 11,111,218 B2
- Document ID: US11111218B2
- Status: Granted
- Kind: B2
- Application number: 15/999,447
- Filed: 2017-02-15
- Published: 2020-11-26
- Granted: 2021-09-07
- Earliest claimed: 2016-02-16
- Assignees: MetrioPharm AG
- Applicants: Metriopharm AG
- Inventors: Thomas Martin; Josef Breu; Juliane Fleissner; Wolfgang Brysch; Jörg Von Wegerer
- Web page: https://patentgrep.com/patent/US11111218B2

## CPC

- C07D 237/32: with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
- 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 9/0073: {Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M)}
- A61K 31/502: ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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 11/00: Drugs for disorders of the respiratory system
- A61P 17/00: Drugs for dermatological disorders
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

A new crystalline form of 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol) is provided. Advantageous uses for this crystalline form as a detecting agent or as an agent for forensic purposes are disclosed, as well a pharmaceutical composition containing said crystalline form.

## Claims

### Claim 1

Crystalline Form II of 5-amino-2,3-dihydrophthalazine-1,4-dione of the following formula:
wherein the crystalline Form II is characterized by a powder X-ray diffraction pattern comprising diffraction peaks at angles (° 2θ) of 7.5°, 12.6°, 13.1°, 13.4°, 25.9°, and 27.2°.

### Claim 2 (depends on 1)

The crystalline Form II according to claim 1, wherein the crystalline Form II is further characterized by a powder X-ray diffraction pattern comprising additional diffraction peaks at angles (° 2θ) of 10.2°, 10.9°, and 26.7°.

### Claim 3 (depends on 1)

A pharmaceutical composition comprising the crystalline Form II according to claim 1 and at least one pharmaceutically acceptable excipient.

### Claim 4 (depends on 3)

The pharmaceutical composition according to claim 3, wherein the at least one pharmaceutically acceptable excipient is selected from the group consisting of an acidifier, an antioxidant, an aromatic substance, a binding agent, a buffer, a carrier, a consistency enhancer, a colorant, a diluent, a disintegrant, an emulsifier, a fatiquor, a flavoring substance, a glidant, a hydrotope, a lubricant, a pH regulator, a permeation enhancer, a preservative, a solubilizing agent, a solvent, a sweetener, and a thickening agent, or a combination thereof.

### Claim 5 (depends on 3)

The pharmaceutical composition according to claim 3, wherein the pharmaceutical composition is administered topically.

### Claim 6 (depends on 3)

The pharmaceutical composition according to claim 3, wherein the pharmaceutical composition further comprises at least one additional pharmaceutically active agent.

### Claim 7 (depends on 1)

A process for producing the crystalline Form II according to claim 1, wherein the process comprises the following steps:
(a) providing a solution of 5-amino-2,3-dihydrophthalazine-1,4-dione sodium salt dissolved in demineralized water;
(b) adding a 10%-38% v/v hydrochloric acid solution to the solution provided in step (a) at a temperature in the range of 5° C. to 50° C. for a period of 1 second to 3600 seconds, to provide a precipitate;
(c) filtering the precipitate provided in step (b);
(d) washing the precipitate provided in step (c) at least one time with demineralized water; and
(e) drying the precipitate provided in step (d) at room temperature for a period of 6 hours to 48 hours, to produce the crystalline Form II according to claim 1.

### Claim 8 (depends on 1, 7)

The process according to claim 7, wherein the process comprises the following steps:
(b) adding a 17% v/v hydrochloric acid solution to the solution provided in step (a) at room temperature for a period of 1800 seconds, to provide a precipitate;
(c) filtering the precipitate provided in step (b);
(d) washing the precipitate provided in step (c) three times with demineralized water; and
(e) drying the precipitate provided in step (d) at room temperature for a period of 12 hours, to produce the crystalline Form II according to claim 1.

### Claim 9 (depends on 1, 7)

The process according to claim 7, wherein step (e) of the process comprises:
(e) drying the precipitate provided in step (d) in a vacuum dryer at a pressure in the range of 5 mbar to 1100 mbar, to produce the crystalline Form II according to claim 1; or
(e) drying the precipitate provided in step (d) in a lyophilizer and removing any residual solvent content by sublimation at 0.1 mbar, to produce the crystalline Form II according to claim 1; or
(e) drying the precipitate provided in step (d) in a rotary evaporator at a pressure in the range of 1 mbar to 1050 mbar, to produce the crystalline Form II according to claim 1.