EP2278980A2

EP2278980A2 - Treatment of migraines without aura in pregnant women by inhalation of dioxygen gas

Info

Publication number: EP2278980A2
Application number: EP09731419A
Authority: EP
Inventors: Marc Lemaire; Nathalie Noel
Original assignee: Air Liquide SA; LAir Liquide SA pour lEtude et lExploitation des Procedes Georges Claude
Current assignee: Air Liquide SA; LAir Liquide SA pour lEtude et lExploitation des Procedes Georges Claude
Priority date: 2008-04-02
Filing date: 2009-03-30
Publication date: 2011-02-02
Also published as: FR2929513B1; CA2711212A1; WO2009125140A3; WO2009125140A2; FR2929513A1

Abstract

Inhalable medicament containing dioxygen gas (O2) in a proportion greater than 22% by volume, intended to treat, minimize or prevent a migraine state of the type without aura in pregnant women.

Description

Treatment of migraines without aura in pregnant women by inhalation of gaseous oxygen

The present invention relates to the use of oxygen (O ₂ ) as an inhalable drug and / or to manufacture an inhalable pharmaceutical composition for treating migraines without aura in pregnant women.

A person is said to have a migraine without aura, commonly referred to as a 'headache', when the following criteria of the International Headache Society (IHS) are met, namely that the person must have been subjected to at least 5 migraine attacks meeting the criteria listed below:

- Headache attacks lasting 4 to 72 hours (without treatment).

- Headache having at least two of the following characteristics: unilateral, pulsatile, moderate or severe, aggravation by routine physical activities, such as climbing or descending stairs. - During headaches, the person is prone to at least one of the following: nausea and / or vomiting, photophobia and / or phonophobia.

- And at least one of the following conditions is met:

. The history, physical and neurological examination of the person does not suggest a coded condition in symptomatic headache groups,. Or these have been dismissed by the complementary investigations,

. Or these exist but migraine attacks have not occurred for the first time in close relationship with these conditions.

Moreover, for pregnant woman means a woman between his ^era the week of gestation and birth of the newborn. Currently, there is no effective therapy for treating migraines without the aura of the pregnant woman due to the potential risks to the fetus or newborn when NSAID-like drugs (anti-inflammatory drugs) are administered. non-steroids), common or specific analgesics, such as Triptans. There is therefore a medical problem which is to be able to provide an effective treatment against migraines without aura in pregnant women who constitute a particular patient population because they can not be treated with conventional drugs because of the risks for the fetus or newborn. The object of the present invention is therefore to provide a pharmaceutical composition, that is to say a drug, effective to treat migraine without having pregnant women.

By effective drug is meant a composition, a substance or a product which, when administered to a pregnant woman suffering from a migraine without aura, allows, on the one hand, to at least decrease and preferentially to make completely disappear the migraine and, on the other hand, does not pose a risk to its fetus or newborn, as in the case of conventional antimigraine drugs.

A solution according to the invention is an inhalable drug containing gaseous oxygen (O 2) in a proportion greater than 22% by volume intended to treat, minimize or prevent an aura-free migraine condition in a pregnant woman, preferably completely or partially treat the intensity of the headache, thus at least decrease the intensity of the headache.

In the context of the present invention: all the gaseous proportions are expressed in percentages by volume that will be written indifferently "%" or "vol. % ".

- the term "medicinal product" is considered to be strictly equivalent to "pharmaceutical composition" or any other similar name.

Depending on the case, the medicament of the invention may comprise one or more of the following characteristics:

it contains a proportion of oxygen greater than 30%, preferably greater than 40%.

it contains a proportion of oxygen greater than 50%.

it contains a proportion of oxygen greater than 70%, typically of the order of 90 to 100%.

it contains a proportion of dioxygen of the order of 100%.

- It contains, in addition, one or more additional compounds selected from nitrogen, helium, argon or xenon.

it is packaged in a gas bottle, preferably in a gas cylinder having a capacity of 0.47 to 5 liters (in water).

- It is intended to be administered during the migraine attack, preferably as soon as possible after the onset of crisis and the administration is continued preferably until complete or partial disappearance of migraine symptoms. - The inhalation time of the pharmaceutical composition is chosen to lead to a disappearance of migraine, preferably the inhalation time is at least 10 minutes, preferably of the order of 15 minutes to 3 hours.

the administration of the oxygen is continuous or discontinuous, preferably continuously, at a flow rate of 0.5 l / min to 30 l / min, preferably of the order of 10 l / min.

In other words, the invention also relates to the use of oxygen gas (O 2) in a proportion greater than 22% by volume to produce an inhalable gaseous drug according to the invention for treating, minimizing or preventing a migraine state. of type without aura in a pregnant woman.

According to the invention, in order to treat migraines without aura, a pregnant woman suffering from such migraine without aura is given a gas rich in oxygen, that is to say containing more than 22% in vol. 'disappearance or alleviation of headache.

Typically, the oxygen-rich gas should preferably contain from about 50 to 100% of O ₂ , and even more preferably more than 70% of O ₂ , for example of the order of 95 to 100% of O ₂ .

The oxygen can be used alone or, as the case may be, diluted with one (or more) other inert gas, in particular with N ₂ , He, Ar or Xe.

The inhalation of gaseous oxygen has a content greater than 22%, advantageously greater than 50%, is done during the migraine attack, preferably as soon as possible after the onset of crisis and is continued preferentially until total or partial disappearance of migraine symptoms without aura.

Advantageously, the inhalation time must be sufficient to lead to a disappearance of the migraine. In general, the inhalation of O ₂ will last at least 10 minutes, preferably of the order of 15 minutes to 3 hours, for example about 30 minutes to 1 hour, at a flow rate of at least 10 1 / min. Such an administration of O ₂ poses no risk for pregnant women because the oxygen (O ₂ ) has no effect of toxicity on the reproductive function, embryo-fetal, perinatal, mutagenic or carcinogenic.

O ₂ may be administered via any gas administration system and in particular by means of a mask or nasal goggles and / or a mouthpiece connected to a source of oxygen-rich gas, for example a a gas cylinder containing the oxygen-rich gas (> 22%) in pre-packaged and ready-to-use form, or a gas mixer to which is connected a source of pure oxygen, such as a bottle of O ₂ or a pipeline of oxygen, and a source of a diluent gas, such as nitrogen or air to allow diluting the oxygen to the desired proportion, or to a mechanical ventilation device fed with oxygen or a gas rich in oxygen to deliver pure oxygen or a mixture containing more than 22% of oxygen. Oxygen administration is continuous or discontinuous, preferably continuously.

The pure dioxygen or the mixture rich in oxygen is preferably packaged in small bottles of gas, typically bottles having a capacity of 0.47 to 5 liters of water, so as to facilitate their transport and / or the ambulation of the patients.

Example

In order to demonstrate the efficacy of such O ₂ administration in pregnant women suffering from migraines without aura, the following test was performed.

A group of about 30 pregnant women with migraines was administered without having:

Test group (25 women): 100% pure O ₂ , control group (5 women): medical air as placebo (with O ₂ content about 21%).

The administration of O ₂ or medical air is via a conventional breathing mask connected to a gas cylinder provided with a flow control tap and / or gas pressure. The duration of continuous administration of the gas is 30 minutes at a rate of 10 liters / minute at the time of the migraine attack.

The main criterion of evaluation is the disappearance of migraine, 120 minutes after the start of administration of the gas (IHS criterion). The results obtained show that, in the Test Group, a significant proportion of pregnant women have a disappearance of their migraine at 120 minutes.

These test results show the therapeutic interest of a use of O ₂ gas in a proportion greater than 22% by volume, preferably greater than 50%, typically of the order of 90 to 100%, as or for producing an inhalable gaseous pharmaceutical composition for treating or preventing an aura-free migraine condition in a pregnant woman.

In other words, the invention also relates to a method of therapeutic treatment of a pregnant woman suffering from migraine without aura, in which the pregnant woman is administered by inhalation a gas or a gaseous mixture containing a proportion of oxygen greater than 22% by volume, preferably greater than 50%, typically of the order of 90 to 100%, ie pure dioxygen.

The administration of O ₂ is preferably continued until the migraine disappears.

Claims

claims

1. Inhalable drug containing gaseous oxygen (O 2) in a proportion greater than 22% by volume for treating, minimizing or preventing an aura-free migraine condition in a pregnant woman.

2. Medicament according to claim 1, characterized in that it contains a proportion of oxygen greater than 30%, preferably greater than 40%.

3. Medicament according to one of claims 1 or 2, characterized in that it contains a proportion of oxygen greater than 50%.

4. Medicament according to one of claims 1 to 3, characterized in that it contains a proportion of oxygen greater than 70%, typically of the order of 90 to 100%.

5. Medicament according to one of claims 1 to 4, characterized in that it contains a proportion of dioxygen of the order of 100%.

6. Medicament according to one of claims 1 to 5, characterized in that it contains, in addition, one or more additional compounds selected from nitrogen, helium, argon or xenon.

7. Medicament according to one of claims 1 to 6, characterized in that it is packaged in a gas bottle, preferably in a gas cylinder having a capacity of 0.47 to 5 liters (in water).

8. Medicament according to one of claims 1 to 7, characterized in that it is intended to be administered during the migraine attack, preferably as soon as possible after the onset of crisis and the administration is continued until total or partial disappearance of migraine symptoms.

9. Medicament according to one of claims 1 to 8, characterized in that the inhalation time of the pharmaceutical composition is chosen to lead to a disappearance migraine, preferably the inhalation time is at least 10 minutes, preferably of the order of 15 minutes to 3 hours.

10. Drug according to one of claims 1 to 9, characterized in that the administration of oxygen is continuous or discontinuous, preferably continuously, at a flow rate of 0.5 1 / min at 30 1 / min, preferably of the order of 10 1 / min.

11. Use of gaseous oxygen (O 2) in a proportion greater than 22% by volume to manufacture an inhalable gaseous drug according to one of claims 1 to 10, for treating, minimizing or preventing a migraine state of type without aura. in a pregnant woman.