In a further aspect the present invention relates to a method of treating or preventing pain in a child comprising administering to said child an effective dosage of an aqueous composition for intranasal administration by spray comprising a mixture of (a) sufentanil, a salt and/or analogs thereof and (b) ketamine, a salt and/or analogs thereof in solution from a pre-filled and ready to use nasal spray device of the present invention. In a further embodiment the pre-filled and ready to use nasal spray device comprising an aqueous composition for intranasal administration by spray comprising a mixture of (a) sufentanil, a salt and/or analogs thereof and (b) ketamine, a salt and/or analogs thereof in solution is located in an emergency vehicle, such as an ambulance. In a still further embodiment the pre-filled and ready to use nasal spray device comprising an aqueous composition for intranasal administration by spray comprising a mixture of (a) sufentanil, a salt and/or analogs thereof and (b) ketamine, a salt and/or analogs thereof in solution is handled by a paramedic. The above described embodiments for the composition also apply for this aspect.

In a further aspect the present invention relates to an aqueous composition for intranasal administration by spray comprising (a) sufentanil, a salt and/or analogs thereof in solution. In an embodiment (a) is sufentanil or a salt thereof. Typically, (a) is a pharmaceutically acceptable acid addition salt of sufentanil. Preferably, (a) is sufentanil citrate. In a still further embodiment (a) is fentanyl or a salt thereof. Typically, (a) is a pharmaceutically acceptable acid addition salt of fentanyl. Preferably, (a) is fentanyl citrate. In a further embodiment (a) is alfentanil or a salt thereof. Typically, (a) is a pharmaceutically acceptable acid addition salt of alfentanil. Preferably, (a) is alfentanil hydrochloride. In a still further embodiment the composition of the present invention has a volume from 25 μl to 5 ml. Typically, the volume is from 0.1 to 2 ml. Preferably, the volume is from 0.5 to 2 ml, such as 1 ml. In a further embodiment the solution contains a buffer. The buffer is able to maintain pH at a constant level, such as a pH between 4 and 8. Thus, e.g. pH may be 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5 or 8, typically 5.0-6.5, such as about 6. The buffer may be any suitable buffer, such as a phosphate buffer or a Citric acid buffer. In a still further embodiment the concentration of (a) is 25-200 μg/ml. Typically, the concentration of (a) is 40-150 μg/ml, such as 40-100 μg/ml, e.g. 50-70 μg/ml. In a further embodiment the concentration of (a) is 65-85 μg/ml. In a still further embodiment the concentration of (a) is 80-100 μg/ml. In a further embodiment the concentration of (a) is 140-160 μg/ml. In a still further embodiment the composition of the present invention further comprises an additional pharmaceutically acceptable additive, such as a preservative. Alternatively, the composition of the present invention may also be sterilized, so as to provide a sterile composition.

In a further aspect the present invention relates to an aqueous composition for intranasal administration by spray comprising (b) ketamine, a salt and/or analogs thereof in solution. In an embodiment (b) is ketamine or a salt thereof. Typically, (b) is a pharmaceutically acceptable acid addition salt of ketamine. Preferably, (b) is ketamine hydrochloride. In a further embodiment (b) is S-ketamine or a salt thereof. Typically, (b) is a pharmaceutically acceptable acid addition salt of S-ketamine. Preferably, (b) is S-ketamine hydrochloride. In a still further embodiment the composition of the present invention has a volume from 25 μl to 5 ml. Typically, the volume is from 0.1 to 2 ml. Preferably, the volume is from 0.5 to 2 ml, such as 1 ml. In a further embodiment the solution contains a buffer. The buffer is able to maintain pH at a constant level, such as a pH between 4 and 8. Thus, e.g. pH may be 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5 or 8, typically 5.0-6.5, such as about 6. The buffer may be any suitable buffer, such as a phosphate buffer or a Citric acid buffer. In a further embodiment the concentration of (b) is 25-200 mg/ml. Typically, the concentration of (b) is 40-150 μg/ml, such as 40-100 μg/ml, e.g. 50-70 μg/ml. In a further embodiment the concentration of (b) is 65-85 mg/ml. In a still further embodiment the concentration of (b) is 80-100 mg/ml. In a further embodiment the concentration of (b) is 140-160 mg/ml. In a still further embodiment the composition of the present invention further comprises an additional pharmaceutically acceptable additive, such as a preservative. Alternatively, the composition of the present invention may also be sterilized, so as to provide a sterile composition.

In a broader aspect the present invention concerns an aqueous composition for intranasal administration by spray comprising (a) sufentanil, a salt and/or analogs thereof in solution and an aqueous composition for intranasal administration by spray comprising (b) ketamine, a salt and/or analogs thereof in solution, for use in a method for the treatment or prevention of pain in a child.

It should be clear that even though the experiments herein are carried out by using a mixture of (a) and (b) in solution, such mixture can take place after (a) and (b) leaves the spray for intranasal delivery or can take place in a mixer chamber as part of a device for intranasal administration by spray, or can even take place from separate nasal spray devices wherein one contains (a) and another contains (b).

In an embodiment the compositions are administered via a pre-filled and ready to use nasal spray device. In a further embodiment the device comprises a first chamber for (a) and a second chamber for (b). In a still further embodiment the device comprises a further chamber for mixing (a) and (b) before intranasal administration by spray. In another embodiment the device is constructed to deliver (a) and (b) separately and simultaneously by intranasal administration by spray.

The above described embodiments for the aqueous composition comprising (a) or (b) also apply for this aspect. In a further embodiment the compositions are administered via a nasal spray device, such as a pre-filled and ready to use nasal spray device, typically, a pre-assembled, pre-filled and ready to use nasal spray device.

In a still further embodiment a dosage volume of 0.05-0.5 ml containing (a) and a dosage volume of 0.05-0.5 ml containing (b) are administered to a nostril of a human subject. Typically, the dosage volume is 0.05-0.3 ml containing (a). Typically, the dosage volume is 0.05-0.3 ml containing (b). In a further embodiment the dosage volume of 0.05-0.1 ml containing (a) and the dosage volume of 0.05-0.1 ml containing (b) are administered one time. In another embodiment the dosage volume of 0.05-0.1 ml containing (a) and the dosage volume of 0.05-0.1 ml containing (b) are administered two times, typically with 10 minutes apart in each nostril. In a still further embodiment the composition of the present invention is for use in a method for the prevention of pain in a child. In a further embodiment the pain is procedural pain. In a still further embodiment the pain is acute pain. In a further embodiment the pain is procedural and acute pain. In a still further embodiment the child is 17 years or younger, such as under 17 years. In a particular embodiment the child is under 2 years, such as under 1 year, e.g. 3-6 months. In a further embodiment the child weighs below 60 kg. In some instances the children weighs below 50 kg, such as below 35 kg, below 25 kg, below 10 kg, all of which constitutes individual embodiments of the present invention.

In a still further aspect the present invention concerns a pre-filled and ready to use nasal spray device comprising an aqueous composition for intranasal administration by spray comprising (a) sufentanil, a salt and/or analogs thereof in solution and an aqueous composition for intranasal administration by spray comprising (b) ketamine, a salt and/or analogs thereof in solution. In an embodiment pre-filled and ready to use nasal spray device is for use in an emergency vehicle, such as an ambulance. The above described embodiments for the compositions also apply for this aspect.