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EP-4740953-A1 - PHARMACEUTICAL COMPOSITION COMPRISING CO2 FOR USE IN THE TREATMENT OF CONDITIONS ASSOCIATED WITH HEADACHE

EP4740953A1EP 4740953 A1EP4740953 A1EP 4740953A1EP-4740953-A1

Abstract

The present invention relates to a pressurized pharmaceutical composition comprising carbon dioxide (CO 2 ) for use in the treatment or prevention of a disorder or condition associated with headache or a disorder or condition involving the trigeminal nervous system in a subject. Furthermore, the present disclosure relates to a device useful for the intranasal application of such compositions. Furthermore, the present invention relates to kits comprising such compositions for use as well as such a device.

Inventors

  • SEIMETZ, Diane
  • BREMER, Chris-Carol
  • LOHRMANN, MARC
  • MEHLER, THOMAS
  • KLEINERT, Regina

Assignees

  • Migrainy UG (haftungsbeschränkt)

Dates

Publication Date
20260513
Application Date
20241108

Claims (15)

  1. A pressurized composition comprising carbon dioxide (CO 2 ) for use - in the treatment or prevention of a disorder or condition associated with headache, or a disorder or condition involving the trigeminal nervous system in a subject, or - in the treatment or prevention of allergic rhinitis, rhinosinusitis, trigeminal neuralgia, post-traumatic headache, temporomandibular joint disorder, epilepsy or seizures in a subject, wherein the composition comprising carbon dioxide is administered to the nasal cavity of the subject by intranasal administration in the form of a gaseous composition comprising carbon dioxide, and wherein the gaseous composition comprising carbon dioxide is administered to the nasal cavity of the subject via both nostrils of the subject.
  2. The composition for use according to claim 1, wherein the pressurized composition comprising carbon dioxide comprises carbon dioxide in a concentration of at least 50 mol-% or of at least 75 mol-% or of at least 90 mol-% (with regard to the total composition).
  3. The composition for use according to claim 1 or 2, wherein the gaseous composition comprising carbon dioxide is administered in the form of a first dose administered within a treatment period of 10 min.
  4. The composition for use according to any one of the preceding claims, wherein the gaseous composition is administered in the form of a sole dose, specifically in the form of a sole dose administered within the treatment period of 10 minutes.
  5. The composition for use according to any one of the preceding claims, wherein during administration of the gaseous composition comprising carbon dioxide the subject does not inhale (breathe)/refrains from inhaling/breathing, specifically, wherein during administration of the gaseous composition comprising carbon dioxide the subject does not inhale (breathe)/refrains from inhaling/breathing through the nose.
  6. The composition for use according to any one of the preceding claims, wherein the disorder or condition or condition associated with headache is migraine.
  7. The composition for use according to any one of the preceding claims, wherein the gaseous composition is administered to the nasal cavity simultaneously via both nostrils of the subject.
  8. The composition for use according to any one of the preceding claims, wherein the gaseous composition is administered to the nasal cavity of the subject at a temperature within range of from about 0 °C to about 18 °C or of from about 5 °C to about 15 °C.
  9. The composition for use according to any one of the preceding claims, wherein the gaseous composition is administered to the nasal cavity of the subject at a pressure within the range of from about 1.5 bar to about 8 bar or of from about 4 bar to about 6 bar.
  10. The composition for use according to any one of the preceding claims, wherein the gaseous composition is administered to the nasal cavity of the subject within a period of from about 5 s to about 30 s.
  11. The composition for use according to any one of the preceding claims, wherein the gaseous composition is administered using an applicator device (1), preferably wherein the applicator device is adapted to generate an atmosphere enriched with carbon dioxide in the nasal cavity of the subject, specifically adapted to generate an atmosphere comprising a concentration of carbon dioxide within the range of from about 70 mol-% to about 99.9 mol-%.
  12. The composition for use according to claim 11, wherein the applicator device (1) comprises: a) a storage unit (10) for holding and/or providing the composition comprising carbon dioxide in pressurized form (12); b) a pre-conditioning unit (20) comprising a pre-conditioning chamber (21) fluidically connected with the storage unit for transforming the composition comprising carbon dioxide in pressurized form into a gaseous composition comprising carbon dioxide (24); and c) an application unit (30) fluidically connected with the pre-conditioning unit (20), specifically with the pre-conditioning chamber (21), for introducing the gaseous composition comprising carbon dioxide into the nasal cavity of the subject via both nostrils of the subject; and optionally d) a housing (40) for holding the storage unit, the pre-conditioning unit, the application unit and optionally further functional units of the applicator device.
  13. The composition for use according to claim 11 or 12, wherein the application device (1) further comprises: e) a control unit (50) for controlling at least one of the amount, pressure, temperature and flow rate at which the gaseous composition comprising carbon dioxide (24) is administered to the nasal cavity of the subject.
  14. An applicator device (1) for the intranasal administration of a gaseous composition comprising carbon dioxide (24) to a subject, preferably for the intranasal administration of the composition comprising carbon dioxide for use according to any one of claims 1 to 13, wherein the application device is adapted for the administration of the gaseous composition comprising carbon dioxide into the nasal cavity of the subject by intranasal administration via both nostrils of the subject, preferably via simultaneous administration via both nostrils of the subject.
  15. The applicator device (1) according to claim 14, wherein the applicator device is a hand-held device that may be held and/or operated with one or two hands of a user.

Description

TECHNICAL FIELD The present invention relates to a pressurized pharmaceutical composition comprising carbon dioxide (CO2) for use in the treatment or prevention of a disorder or condition associated with headache or a disorder or condition involving the trigeminal nervous system in a subject. Furthermore, the present disclosure relates to a device useful for the intranasal application of such compositions. Furthermore, the present invention relates to kits comprising such compositions for use as well as such a device. In general, the present disclosure relates to pressurized compositions comprising carbon dioxide for use in the treatment or prevention of conditions or disorders associated with headache such as migraine. More particularly, this invention is concerned with alleviating migraine and other headache-associated disorders by administering pressurized compositions comprising carbon dioxide intranasally. The invention further pertains to pressurized compositions comprising carbon dioxide for use in the treatment or prevention of conditions involving the trigeminal nerve system, CGRP-involving reactions, pH shift, temporomandibular joint disorder, post-traumatic headache, and/or secondary headache. BACKGROUND Migraine is a type of headache characterized by recurrent attacks of moderate to severe throbbing and pulsating pain on one or both sides of the head. The pain is, amongst others, caused by the activation of nerve fibers within the wall of brain blood vessels traveling inside the meninges (three layers of membranes protecting the brain and spinal cord). Untreated attacks last from four to 72 hours. Other common symptoms include increased sensitivity to light, noise, and odors; nausea; and vomiting. The two major types of migraine are (i) migraine with aura, previously called classic migraine, which includes visual disturbances and other neurological symptoms that appear about 10 to 60 minutes before the actual headache and usually last no more than an hour; and (ii) migraine without aura, or common migraine, which is the more frequent form of migraine. Examples of triggers of migraine are: stress related, e.g., anxiety, anger, worry, excitement, shock, depression, overexertion, changes of routine and changes of climate, food-related, e.g., chocolate, cheese and other dairy products, red wine, fried food and citrus fruits, sensory-related, e.g., bright lights or glare, loud noises and intense or penetrating smells, hormonal changes, menstruation and contraceptive drugs. Migraine affects approximately 8% of the global population. Migraine also most commonly occurs at productive age, in which the frequency of migraine headache days correlate with increased disability, leading to a decreased quality of life involving negative psychological impacts on performances within social and familial contexts. Moreover, the disease represents a significant burden to the health care system. The pathophysiology of migraine remains poorly understood. However, some specific vasoactive substances and neurotransmitters probably play a role in the mechanism of neurovascular and cortical spreading depression. Calcitonin gene-related peptide (CGRP), neurokinin A, nitric oxide, and substance P are released with perivascular nerve activity. They likely interact with the blood vessel wall, causing dilation, protein extravasation, and sterile inflammation. The stimulation of the trigeminocervical complex by these chemical substances is relayed to the thalamus and cortex, both of which register pain. Known drugs for the treatment of migraine include acetaminophen, nonsteroidal anti- inflammatory drugs (NSAIDs), triptans, antiemetics, ergot alkaloids, and combination analgesics. Acetaminophen and nonsteroidal anti-inflammatory drugs are first-line treatments for mild to moderate migraines, whereas triptans are first-line treatments for moderate to severe migraines. Although triptans are effective, they may not be (sufficiently) effective in all patients. Other medications such as dihydroergotamine and antiemetics are recommended for use as second- or third-line therapy for select patients or for those with refractory migraine. Calcitonin gene-related peptide (CGRP) antagonists are a class of medications that act as antagonists of the CGRP receptor or ligand. They can be divided into monoclonal antibodies and non-peptide small molecules, also known as gepants. CGRP antagonists were the first oral agents specifically designed to prevent migraines. Some patients, however, respond only poorly or not at all to CGRP antagonists. Administration of carbon dioxide has also been proposed as treatment option for migraine, see, e.g., US 2023/0166061 A1, WO 2001/064280 A1, and US 7,017,573 B1. C. Vause et al. report in Headache. 2007; 47(10): 1385-1397 on the effect of carbon dioxide on calcitonin gene-related peptide secretion from trigeminal neurons. The authors report that CO2 treatment under isohydric conditions resulted in a decrease