COMBINATION COMPOSITION

Abstract

An intravenous composition for providing relief for pain and/or inflammation, the composition having ibuprofen and paracetamol in combination for delivering to a human at each dose: a) approximately 125 mg to approximately 175 mg ibuprofen in combination with approximately 475 mg to approximately 525 mg paracetamol; or b) approximately 275 mg to approximately 325 mg ibuprofen in combination with approximately 975 mg to approximately 1,025 mg paracetamol.

Claims

1. A method of treating pain by intravenously administering to a human, 100 ml of an aqueous solution comprising: a) 150 mg ibuprofen in combination with 500 mg paracetamol; or b) 300 mg ibuprofen in combination with 1000 mg paracetamol.

2. The method according to claim 1, wherein the aqueous solution is administered on a 6 hourly basis.

3. The method of claim 1, wherein the aqueous solution comprises 150 mg ibuprofen in combination with 500 mg paracetamol.

4. The method of claim 1, wherein the aqueous solution comprises 300 mg ibuprofen in combination with 1000 mg paracetamol.

5. The method of claim 2, wherein the aqueous solution comprises 150 mg ibuprofen in combination with 500 mg paracetamol.

6. The method of claim 2, wherein the aqueous solution comprises 300 mg ibuprofen in combination with 1000 mg paracetamol.

7. A method of treating pain by intravenously administering to a human, an aqueous solution comprising: a) 150 mg ibuprofen in combination with 500 mg paracetamol; or b) 300 mg ibuprofen in combination with 1000 mg paracetamol, wherein the administration takes place over 15 minutes.

8. The method according to claim 7, wherein the aqueous solution is administered on a 6 hourly basis.

9. The method of claim 7, wherein the aqueous solution comprises 150 mg ibuprofen in combination with 500 mg paracetamol.

10. The method of claim 7, wherein the aqueous solution comprises 300 mg ibuprofen in combination with 1000 mg paracetamol.

11. The method of claim 8, wherein the aqueous solution comprises 150 mg ibuprofen in combination with 500 mg paracetamol.

12. The method of claim 8, wherein the aqueous solution comprises 300 mg ibuprofen in combination with 1000 mg paracetamol.

13. A method of treating pain by intravenously administering to a human, 100 ml of an aqueous solution comprising: a) 150 mg ibuprofen in combination with 500 mg paracetamol; or b) 300 mg ibuprofen in combination with 1000 mg paracetamol, wherein the administration takes place over 15 minutes.

14. The method according to claim 13, wherein the aqueous solution is administered on a 6 hourly basis.

15. The method of claim 13, wherein the aqueous solution comprises 150 mg ibuprofen in combination with 500 mg paracetamol.

16. The method of claim 13, wherein the aqueous solution comprises 300 mg ibuprofen in combination with 1000 mg paracetamol.

17. The method of claim 14, wherein the aqueous solution comprises 150 mg ibuprofen in combination with 500 mg paracetamol.

18. The method of claim 14, wherein the aqueous solution comprises 300 mg ibuprofen in combination with 1000 mg paracetamol.

Description

DETAILED DESCRIPTION

[0032] In a preferred embodiment of the invention an intravenous solution is provided for use in treating pain or inflammation in human patients. The solution is a combination medication comprising ibuprofen, paracetamol and suitable excipients as will be known to those with ordinary skills in the art of formulating intravenous medicines. The excipients may include suitable antioxidants, pH modulators, buffering agents isotonicity agents and purified water.

[0033] The following examples illustrate preferred embodiments of the invention in the form of intravenous infusion solutions.

TABLE-US-00001 Example 1 Example 2 mg/100 ml mg/100 ml Ingredient vial vial Ibuprofen 150 300 Paracetamol 500 1,000

[0034] For each of the above examples the two active ingredients are mixed with suitable standard excipients to give the vial volumes indicated above.

[0035] The infusion solutions are for delivery to a patient as a full dose, for example in each case the patient receives the complete vial contents as a 15 minute infusion every 6 hours. Example 1 is a child's dose and Example 2 is an adult dose. In the case of very young or small children only part of the vial contents of Example 1 may be dosed on a body weight basis, commensurate with instructions from the prescribing physician.

[0036] Paracetamol at 4,000 mg per 24 hour period, taken in 4 doses of 1,000 mg every 6 hours, has long been considered sufficient for relieving low level pain but for many patients suffering significant pain, for example in some post operative situations, it is not sufficient. However it is generally not advisable to dose paracetamol at more than 1,000 mg per dose or at more than 4,000 mg per 24 hour period, because to do so can lead to undesirable side effects.

[0037] It is known to treat severe pain with ibuprofen in doses of 800 mg every 8 hours. However, doses as high as 800 mg can lead to undesirable side effects, for example adverse cardio renal conditions, renal problems, thrombotic risks and gastrointestinal bleeding. Reducing the amount of ibuprofen at each dosing event may reduce the risk of side effects but at the same time may provide substantially less pain relief.

[0038] Surprisingly, an intravenous medicine comprising 150 mg or 300 mg ibuprofen, plus 500 mg or 1,000 mg paracetamol, respectively, for use every 6 hours, provides adequate pain relief for some patients that would otherwise need to take, respectively, 400 mg or 800 mg every 8 hours. The lower dose of ibuprofen reduces the risk of undesirable side effects in some patients but the effectiveness of the medication for such patients is not compromised due to the presence of the paracetamol. This is unexpected because for many patients one would not predict the presence of paracetamol to assist to any significant degree. The combination is counterintuitive because, for example, 400 mg ibuprofen for relief of pain is generally seen as an 8 hourly medicament, and 1,000 mg paracetamol is generally seen as a 6 hourly medicament. The normal dosage regimens for these active ingredients are out of step with one another, ie 8 hourly versus 6 hourly, and thus to the normally skilled artesian they would not, at the doses of the present invention, be seen as suitable for a combination medication.

[0039] Similar considerations apply in the case of 150 mg ibuprofen, in combination with 500 mg paracetamol, for treating children suffering from pain. In this regard, surprisingly, some children that would normally be given 200 mg ibuprofen for pain can be given, as an alternative, 150 mg ibuprofen in combination with 500 mg paracetamol.

[0040] Administering an intravenous combination solution comprising 300 mg ibuprofen plus 1,000 mg paracetamol to an adult, or an intravenous combination solution comprising 150 mg ibuprofen plus 500 mg paracetamol to a child, on an ongoing basis, for example every 6 hours, provides a surprising level of pain relief compared to administering the same doses orally, for example by way of a tablet. The intravenous administration reduces the need for rescue pain relief in at least some patients recovering from surgical procedures. The intravenous administration may for example be by way of injection or infusion.

Example 3

[0041] In a particular embodiment of the invention an intravenous solution may be prepared by mixing the following active ingredients and excipients:

TABLE-US-00002 ACTIVE INGREDIENTS AMOUNT Paracetamol 1000 mg Ibuprofen arginine  553 mg EXCIPIENTS AMOUNT Reduced glutathione (as antioxidant)  20 mg Sodium hydroxide or hydrochloric sufficient to give acid (as a pH modulator) a pH of 5-6 Sodium citrate  10 mg Sodium chloride sufficient to impart (as an isotonicity agent) isotonicity Purified water Sufficient to bring the composition to 100 ml

[0042] The solution is for administration to an adult as a single intravenous dose and further equivalent doses may be repeated every 6 hours if need be, commensurate with instructions from the prescribing physician.

Example 4

[0043] In a further embodiment of the invention an intravenous solution may be prepared by mixing the following active ingredients and excipients:

TABLE-US-00003 ACTIVE INGREDIENTS AMOUNT Paracetamol   500 mg Ibuprofen arginine 276.5 mg EXCIPIENTS AMOUNT Reduced glutathione   10 mg (as antioxidant) Sodium hydroxide or hydrochloric sufficient to acid (as a pH modulator) give a pH of 5-6 Sodium citrate    5 mg (as a buffering agent) Sodium chloride sufficient to (as an isotonicityagent) impart isotonicity Purified water Sufficient to bring the composition to 100 ml

[0044] The solution is for administration to a child as a single intravenous dose and further equivalent doses may be repeated every 6 hours if need be, commensurate with instructions from the prescribing physician.

[0045] While some preferred forms of the invention have been described by way of example it should be appreciated that modifications and improvements can occur without departing from the scope of the following claims.