AU2023230563A1

AU2023230563A1 - Medication

Info

Publication number: AU2023230563A1
Application number: AU2023230563A
Authority: AU
Inventors: Hartley Atkinson
Original assignee: AFT Pharmaceuticals Ltd
Current assignee: AFT Pharmaceuticals Ltd
Priority date: 2022-03-08
Filing date: 2023-02-23
Publication date: 2024-09-05
Also published as: EP4489751A1; EP4489751A4; AU2023222825A1; WO2023172148A1; AU2022201576A1

Abstract

This invention relates to the use of paracetamol, ibuprofen and xylometazoline (or a pharmaceutically acceptable salt thereof) in the production of a medication for use in treating cold and/or flu in a human, by administering or taking: a) 1,000 mg (±5%) paracetamol, orally; b) 300 mg (±5%) ibuprofen orally; and c) 0.12 mg (±5%) xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied as one or more droplets, into each nostril.

Description

TITLE

Medication

FIELD OF INVENTION

This invention relates to medication for use in treating cold or flu.

BACKGROUND

Cold and flu in humans are associated with body aches, pain and congestion of the nasal passages. It is desirable to overcome or to remediate these symptoms as the affected person recovers. It is an object of the invention to go at least some way towards achieving this.

DEFINITIONS

The term “comprises” or “has”, if and when used in this document in connection with a combination of features, should not be seen as excluding the option of further features that have not been mentioned. The same applies to derivative terms such as “comprising” and “having”.

References in this document to a “day” mean a 24 hour period.

In this document a weight amounts are given forxylometazoline per se and it should be understood that these applies to the amount of xylometazoline base. When in salt form the weight will be higher depending on the molecular weight of the salt component. By way of example, 0.12 mg xylometazoline base weighs about the same as 0.14 mg of xylometazoline hydrochloride, i.e. on account of the extra weight attributable to the hydrochloride component.

SUMMARY OF THE INVENTION

First Aspect - Use in Manufacture

According to one aspect, the invention involves the use of paracetamol, ibuprofen and xylometazoline (or a pharmaceutically acceptable salt thereof) in the production of a medication for use in treating cold and/or flu in a human, by administering or taking (optionally during the same day): a) 1 ,000 mg (±5%) paracetamol, orally; b) 300 mg (±5%) ibuprofen orally; and c) 0.12 mg (±5%) xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied [e.g. via a dropper] as one or more droplets, into each nostril.

Optionally the medication is for use in treating cold and/or flu in a human, by administering or taking (optionally during the same day): a) about 1 ,000 mg paracetamol orally, about 300 mg ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed into each nostril; or b) about 975 mg paracetamol orally, about 293 mg (e.g. 292.5 mg) ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed into each nostril.

Optionally the paracetamol, ibuprofen and xylometazoline (or the pharmaceutically acceptable salt) are for administering or taking at the same dosage event, on at least some occasions during the same day.

Optionally the paracetamol and ibuprofen are for administering or taking at the same dosage event, and the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking at a different dosage event, on at least some occasions during the same day.

Optionally the medication is such that the paracetamol and ibuprofen are for administering or taking in the amounts stated four times each day, and the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking in the amount stated two to three times during the same day.

Optionally the medication is such that the paracetamol and ibuprofen are for administering or taking in one or more uniform combination tablets or capsules.

Optionally the medication is such that the amounts of paracetamol and ibuprofen are for administering or taking in two or three uniform combination tablets or capsules. Optionally the medication is such that the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking in a liquid carrier.

Optionally the xylometazoline (or the pharmaceutically acceptable salt) is in the form of the pharmaceutically acceptable salt, for example xylometazoline hydrochloride.

Optionally the medication is such that the xylometazoline hydrochloride is for administering or taking in an amount of about 0.14 mg per nostril each time the xylometazoline hydrochloride is taken or administered.

Second Aspect - Method of Treatment

According to a further aspect, the invention involves a method of treating cold and/or flu in a human, comprising administering or taking (optionally during the same day): a) 1 ,000 mg (±5%) paracetamol orally; b) 300 mg (±5%) ibuprofen orally; and c) 0.12 mg (±5%) xylometazoline (or an equivalent amount of a pharmaceutically acceptable salt thereof) sprayed, or applied [e.g. via a dropper] as one or more droplets, into each nostril.

Optionally the method comprises administering or taking (optionally during the same day): a) about 1 ,000 mg paracetamol orally, about 300 mg ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied [e.g. via a dropper] as one or more droplets, into each nostril; or b) about 975 mg paracetamol orally, about 293 mg (e.g. about 292.5 mg) ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied [e.g. via a dropper] as one or more droplets, into each nostril.

Optionally the paracetamol, ibuprofen and xylometazoline (or the pharmaceutically acceptable salt) are administered or taken at the same dosage event on at least some occasions during the same day. Optionally the paracetamol and ibuprofen are taken or administered at the same dosage event, and the xylometazoline (or the pharmaceutically acceptable salt) is administered or taken at a different dosage event, on at least some occasions during the same day.

Optionally the paracetamol and ibuprofen are administered or taken in the amounts stated four times each day, and the xylometazoline (or the pharmaceutically acceptable salt) is administered or taken in the amount stated two to three times in the same day.

Optionally the paracetamol and ibuprofen are administered or taken in one or more uniform combination tablets or capsules.

Optionally the amounts of paracetamol and ibuprofen are administered or taken in two or three uniform combination tablets or capsules.

Optionally the xylometazoline (or the pharmaceutically acceptable salt) is in a liquid carrier.

Optionally the method comprises administering or taking the pharmaceutically acceptable salt, for example xylometazoline hydrochloride.

Optionally the xylometazoline hydrochloride is administered or taken in an amount of about 0.14 mg per nostril each time the xylometazoline hydrochloride is taken or administered.

Third Aspect - Product for Use in Treatment

According to a third aspect, the invention involves a medication comprising paracetamol, ibuprofen and xylometazoline (or a pharmaceutically acceptable salt thereof), for use in treating cold and/or flu in a human by administering or taking (optionally during the same day): a) 1 ,000 mg (±5%) paracetamol orally; b) 300 mg (±5%) ibuprofen orally; and c) 0.12 mg (±5%) xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied [e.g. via a dropper] as one or more droplets, into each nostril. Optionally the medication is for use in treating cold and/or flu in a human by administering or taking (optionally during the same day): a) about 1 ,000 mg paracetamol orally, about 300 mg ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied [e.g. via a dropper] as one or more droplets, into each nostril; or b) about 975 mg paracetamol orally, about 293 mg (e.g. about 292.5 mg) ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied [e.g. via a dropper] as one or more droplets, into each nostril.

Optionally the paracetamol and ibuprofen are for administering or taking in the amounts stated four times each day, and the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking in the amount stated two to three times during the same day.

Optionally the paracetamol and ibuprofen are for administering or taking in one or more uniform combination tablets or capsules.

Optionally the medication is such that the amounts of paracetamol and ibuprofen are for administering or taking in two or three uniform combination tablets or capsules.

Optionally the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking in a liquid carrier. Optionally the pharmaceutically acceptable salt, for example xylometazoline hydrochloride.

Optionally the xylometazoline hydrochloride is for administering or taking in an amount of about 0.14 mg per nostril each time the xylometazoline hydrochloride is taken or administered.

DETAILED DESCRIPTION

In a preferred embodiment the invention involves a medication comprising the active agents paracetamol, ibuprofen and xylometazoline, and the use of the medication, for treating cold and/or flu in a human.

The paracetamol and ibuprofen are for oral administration and the xylometazoline is for administration as a nasal spray. The medication may therefore be in the form of a pack or kit of more than one dosage form. For example the paracetamol and ibuprofen are preferably in the form of tablets or capsules where each of these comprises a combination of both actives. The xylometazoline is preferably in the form of a nasal spray, the active being dissolved or suspended in a suitable carrier liquid, preferably an aqueous carrier, in a spray bottle.

In some embodiments the paracetamol and ibuprofen may be in different tablets or capsules, and the xylometazoline may be in a liquid, preferably aqueous, carrier in a spray bottle.

Preferably the paracetamol is taken at each dosage event in the amount 1 ,000 mg or 975 mg orally, split evenly between two or three tablets or capsules. And preferably the ibuprofen is taken at each dosage event in the amount 300 mg, split evenly between the same two or three tablets or capsules. For example each tablet or capsule may comprise 500 mg paracetamol + 150 mg ibuprofen, or 325 mg paracetamol + about 98 (e.g. 97.5) mg ibuprofen.

Preferably the xylometazoline is taken as one spray of a 1 mg/ml xylometazoline hydrochloride aqueous solution per nostril. This equates with about 0.14 mg xylometazoline hydrochloride, or 0.12 mg xylometazoline base, per nostril. Preferably the paracetamol and ibuprofen are taken in the amounts mentioned at each dosage event up to four times daily, and the xylometazoline is taken in the amount mentioned at dosage event up to two or three time daily. The dosage events for taking paracetamol + ibuprofen may or may not coincide with the dosage events for taking the xylometazoline. On at least some occasions all three may be taken at the same time, and on at least some occasions just the paracetamol + ibuprofen may be taken, or just the xylometazoline.

Clinical Trial

A randomised, single dose, three-way crossover open label study was run to evaluate the pharmacokinetic parameters of paracetamol and ibuprofen taken orally and xylometazoline hydrochloride sprayed into the nostrils.

The trial involved 30 healthy adult participants, aged 18-50, who were each given Treatment A, B or C below under fasting conditions (10 hours fasting prior, and 4 hours fasting after).

The participants had not taken any prescription medications for 14 days, or over-the- counter medications for 7 days, prior to the trial except for contraceptives in the case of fertile female participants. During the trial only the test medications were taken, except for contraceptives as above. At the conclusion of the trial blood samples were drawn from the participants over a 12 hour period. The samples were collected 10, 20, 30, 45, 60, 85, 110, 120, 180, 240, 360, 480, 600 and 720 minutes after administering Treatments A, B and C.

The blood samples were tested for C_max, or in otherwise to see what the maximum concentration of active ingredient was in the blood, and also T_max, or in other words the time it took to get to the maximum concentration in the blood. The trial results are as follows.

Ibuprofen Uptake

The results show that when ibuprofen + paracetamol is taken with xylometazoline, the Cmax (maximum blood concentration) achieved for the ibuprofen is 10% less than when taken without xylometazoline. Further, the sample that included xylometazoline has a Tmax 33% greater, meaning that it took 33% longer for the ibuprofen to get to its maximum blood concentration. The lowered Cmax coupled with the increased Tmax means that ibuprofen was delivered to the blood in a more even or sustained-relief manner. It is commensurate with likely improved tolerability and a smoothed-out absorption profile. It is believed to reduce or avoid the need for a sustained release tablet matrix when formulating a medication.

The results were surprising because one would not expect xylometazoline to have any impact on the uptake of orally ingested ibuprofen. In this regard it is notable that the results did not show any significant difference in the uptake of the paracetamol or of the xylometazoline hydrochloride.

The above findings are significant in that it is reported by researchers that higher doses of NSAIDs (e.g. ibuprofen), and also paracetamol, may be associated with a greater risk of hypertension. By combining xylometazoline with ibuprofen or another NSAID these risks may be reduced through moderating the impact of the NSAID (e.g. ibuprofen).

Optionally for all embodiments of the invention the medication is taken daily for at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days , 8 days, 9 days 10 days. Optionally for all embodiments the medication is taken daily for 4-5 days, 4-6 days, 4-7 days, 4-8 days, 4-9 days or 4-10 days.

While some forms of the invention have been described by way of example it should be appreciated that modifications and improvements can be made without departing from the scope of the accompanying claims.

In terms of disclosure, this document envisages and hereby posits any feature mentioned herein in combination with itself or any other feature or features mentioned herein, even if the combination is not claimed.

Claims

1. Use of paracetamol, ibuprofen and xylometazoline (or a pharmaceutically acceptable salt thereof) in the production of a medication for use in treating cold and/or flu in a human, by administering or taking (optionally during the same day): a) 1 ,000 mg (±5%) paracetamol, orally; b) 300 mg (±5%) ibuprofen orally; and c) 0.12 mg (±5%) xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied as one or more droplets, into each nostril.

2. The use of claim 1 , where the medication is for use in treating cold and/or flu in a human, by administering or taking (optionally during the same day): a) about 1 ,000 mg paracetamol orally, about 300 mg ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed , or applied as one or more droplets, into each nostril; or b) about 975 mg paracetamol orally, about 293 mg ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied as one or more droplets, into each nostril.

3. The use according to claim 1 or 2, where the paracetamol, ibuprofen and xylometazoline (or the pharmaceutically acceptable salt) are for administering or taking at the same dosage event, on at least some occasions during the same day.

4. The use according to claim 1 or 2, where the paracetamol and ibuprofen are for administering or taking at the same dosage event, and the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking at a different dosage event, on at least some occasions during the same day.

5. The use of any one of claims 1 -4, where the medication is such that the paracetamol and ibuprofen are for administering or taking in the amounts stated four times each day, and the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking in the amount stated two to three times during the same day. The use of any one of the preceding claims, where the medication is such that the paracetamol and ibuprofen are for administering or taking in one or more uniform combination tablets or capsules. The use of any one of the preceding claims, where the medication is such that the amounts of paracetamol and ibuprofen are for administering or taking in two or three uniform combination tablets or capsules. The use of any one of the preceding claims, where the medication is such that the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking in a liquid carrier. A use of any one of the preceding claims, wherein the xylometazoline (or the pharmaceutically acceptable salt) is in the form of the pharmaceutically acceptable salt, for example xylometazoline hydrochloride. The use according to claim 9, where the medication is such that the xylometazoline hydrochloride is for administering or taking in an amount of about 0.14 mg per nostril each time the xylometazoline hydrochloride is taken or administered. A method of treating cold and/or flu in a human, comprising administering or taking during a day: a) 1 ,000 mg (±5%) paracetamol orally; b) 300 mg (±5%) ibuprofen orally; and c) 0.12 mg (±5%) xylometazoline (or an equivalent amount of a pharmaceutically acceptable salt thereof) sprayed, or applied as one or more droplets, into each nostril. The method of claim 11 , comprising administering or taking during a day: a) about 1 ,000 mg paracetamol orally, about 300 mg ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied as one or more droplets, into each nostril; or b) about 975 mg paracetamol orally, about 293 mg ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied as one or more droplets, into each nostril. The method of claim 11 or 12, where the paracetamol, ibuprofen and xylometazoline (or the pharmaceutically acceptable salt) are administered or taken at the same dosage event on at least some occasions during the same day. The method of claim 11 or 12, where the paracetamol and ibuprofen are taken or administered at the same dosage event, and the xylometazoline (or the pharmaceutically acceptable salt) is administered or taken at a different dosage event, on at least some occasions during the same day. The method of any one of claims 10-14, where the paracetamol and ibuprofen are administered or taken in the amounts stated four times each day, and the xylometazoline (or the pharmaceutically acceptable salt) is administered or taken in the amount stated two to three times in the same day. The method of any one of claims 10-15, where the paracetamol and ibuprofen are administered or taken in one or more uniform combination tablets or capsules. The method of any one of claims 10-16, where the amounts of paracetamol and ibuprofen are administered or taken in two or three uniform combination tablets or capsules. The method of any one of claims 10-17, where the xylometazoline (or the pharmaceutically acceptable salt) is in a liquid carrier. The method of any one of claims 10-18, comprising administering or taking the pharmaceutically acceptable salt, for example xylometazoline hydrochloride. The method of any one of claims 10-19, where the xylometazoline hydrochloride is administered or taken in an amount of about 0.14 mg per nostril each time the xylometazoline hydrochloride is taken or administered. Medication comprising paracetamol, ibuprofen and xylometazoline (or a pharmaceutically acceptable salt thereof), for use in treating cold and/or flu in a human by administering or taking (optionally during the same day): a) 1 ,000 mg (±5%) paracetamol orally; b) 300 mg (±5%) ibuprofen orally; and c) 0.12 mg (±5%) xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied as one or more droplets, into each nostril. Medication according to claim 21 , for use in treating cold and/or flu in a human by administering or taking (optionally during the same day): a) about 1 ,000 mg paracetamol orally, about 300 mg ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied as one or more droplets, into each nostril; or b) about 975 mg paracetamol orally, about 293 mg ibuprofen orally, and about 0.12 mg xylometazoline (or an equivalent amount of the pharmaceutically acceptable salt) sprayed, or applied as one or more droplets, into each nostril. Medication according to claim 21 or 22, wherein the paracetamol, ibuprofen and xylometazoline (or the pharmaceutically acceptable salt) are for administering or taking at the same dosage event, on at least some occasions during the same day. Medication according to claim 21 or 22, wherein the paracetamol and ibuprofen are for administering or taking at the same dosage event, and the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking at a different dosage event, on at least some occasions during the same day. Medication according to any one of claims 21-24, where the paracetamol and ibuprofen are for administering or taking in the amounts stated four times each day, and the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking in the amount stated two to three times during the same day. Medication according to any one of claims 21-25, where the paracetamol and ibuprofen are for administering or taking in one or more uniform combination tablets or capsules. Medication according to any one of claims 21-26, where the medication is such that the amounts of paracetamol and ibuprofen are for administering or taking in two or three uniform combination tablets or capsules. Medication according to any one of claims 21-27, where the xylometazoline (or the pharmaceutically acceptable salt) is for administering or taking in a liquid carrier. Medication according to any one of claims 21-24, comprising the pharmaceutically acceptable salt, for example xylometazoline hydrochloride. Medication according to claim 29, where the xylometazoline hydrochloride is for administering or taking in an amount of about 0.14 mg per nostril each time the xylometazoline hydrochloride is taken or administered.