Thermogelling anaesthetic compositions
View Patent ↗The present invention relates to a thermogelling pharmaceutical composition comprising local anaesthetics in base form and which is suitable for topical administration. The compositions further comprise a polyoxyethylene castor oil and one or more surfactants to obtain thermogelling characteristics.
1. A pharmaceutical composition comprising:
(a) 1 to 10% by weight of one or more local anaesthetics in base form solubilized in 10 to 30% by weight of a polyoxyethylene castor oil, said one or more local anaesthetics being selected from the group consisting of lidocaine, prilocaine, mepivacaine, ropivacaine, bupivacaine, and levobupivacaine;
(b) 15% to 30% by weight of one or more non-ionic block copolymers of poly(oxyethylene) and poly(oxypropylene) type; and
(c) water,
wherein the pH of the composition is at least the value of the lowest pK a of said one or more local anaesthetics.
2. A method of treating pain during an obstetric or gynaecological procedure which method comprises:
(i) providing in a container a composition comprising:
1 to 10% by weight of one or more local anaesthetics in base form solubilized in 10 to 30% by weight of a polyoxyethylene castor oil, said one or more local anaesthetics being selected from the group consisting of lidocaine, prilocaine, mepivacaine, ropivacaine, bupivacaine, and levobupivacaine,
15 to 30% by weight of one or more non-ionic block copolymers of poly(oxyethylene) and poly(oxypropylene) type, and
water,
wherein the pH of the composition is at least the value of the lowest pK a of said one or more local anaesthetics; and
(ii) applying said composition from said container to an internal mucosal surface of a patient in need of such pain treatment by intravaginal, intracervical, pericervical or intrauteral administration wherein the composition after said applying forms a thermogel on said mucosal surface.
3. The method according to claim 2 wherein said one or more local anesthetics is lidocaine, prilocaine, mepivacaine, or any combination thereof.
4. The method according to claim 2 wherein said application is carried out during an obstetric procedure.
5. The method according to claim 4 wherein said obstetric procedure is labour.
6. The method according to claim 2 wherein said application is carried out during a gynaecological procedure.
7. The method according to claim 6 wherein said gynaecological procedure is an abortion, application of an intrauterine device, a hysteroscopy, in vitro fertilization or a general vaginal examination.
8. The method according to claim 2 wherein the composition further comprises an additional solubilizer in an amount of 1 to 5% by weight.
9. The method according to claim 8 wherein the additional solubilizer is a lower alcohol.
10. The method according to claim 8 wherein the additional solubilizer is selected from the group consisting of glycerol formal, glycofural, polysorbate 80, and ethyl acetate.
11. The method according to claim 2 wherein the amount of the one or more local anaesthetics is 1 to 7% by weight.
12. The method according to claim 2 wherein the amount of the one or more local anaesthetics is 3 to 5% by weight.
13. The method according to claim 2 wherein the polyoxyethylene castor oil is polyoxyethylene 35 castor oil.
14. The method according to claim 2 wherein the block copolymers comprise a higher molecular weight poloxamer and a lower molecular weight poloxamer, and wherein the higher molecular weight poloxamer and the lower molecular weight poloxamer are present in about equal amounts.
15. The method according to claim 2 wherein the block copolymers are poloxamer 188 and poloxamer 407.
16. The method according to claim 3 wherein the composition has an elasticity modulus (G′) below 20 Pa at room temperature and an elasticity modulus (G′) in the range of 50 to 10000 PA at body temperature.
17. A method of treating pain during an obstetric or gynaecological procedure which method consists essentially of:
(i) application to a mucosal surface of a patient in need of such pain treatment of a composition comprising:
1 to 10% by weight of one or more local anaesthetics solubilized in 10 to 30% by weight of a polyoxyethylene castor oil, said one or more local anaesthetics being selected from the group consisting of lidocaine, prilocaine, mepivacaine, ropivacaine, bupivacaine, and levobupivacaine,
15 to 30% by weight of one or more non-ionic block copolymers of poly(oxyethylene) and poly(oxypropylene) type, and
water, wherein the pH of the composition is at least the value of the lowest pK a of said one or more local anaesthetics, and
wherein said application is carried out by intravaginal, intracervical, pericervical or intrauteral administration of said composition; and
(ii) formation of a thermogel on said mucosal surface.
18. The pharmaceutical composition according to claim 1 wherein the one or more local anaesthetics is lidocaine, prilocaine, mepivacaine, or any combination thereof.
19. The pharmaceutical composition according to claim 1 wherein the composition further comprises and additional solubilizer in an amount of 1 to 5% by weight.
20. The pharmaceutical composition according to claim 19 wherein the additional solubilizer is a lower alcohol.
21. The pharmaceutical composition according to claim 19 wherein the additional solubilizer is selected from the group consisting of glycerol formal, glycofural, polysorbate 80, and ethyl acetate.
22. The pharmaceutical composition according to claim 1 wherein the amount of the one or more local anaesthetics is 1 to 7% by weight.
23. The pharmaceutical composition according to claim 1 wherein the amount of the one or more local anaesthetics is 3 to 5% by weight.
24. The pharmaceutical composition according to claim 1 wherein the polyoxyethylene castor oil is polyoxyethylene 35 castor oil.
25. The pharmaceutical composition according to claim 1 wherein the block copolymers comprise a higher molecular weight poloxamer and a lower molecular weight poloxamer, and wherein the higher molecular weight poloxamer and the lower molecular weight poloxamer are present in about equal amounts.
26. The pharmaceutical composition according to claim 1 wherein the block copolymers are poloxamer 188 and poloxamer 407.
27. The pharmaceutical composition according to claim 1 wherein the composition has an elasticity modulus (G′) below 20 Pa at room temperature and an elasticity modulus (G′) in the range of 50 to 10000 PA at body temperature.