Ready-to-use esthetic compositions
Described are ready-to-use injectable compositions comprising polymeric microspheres or microparticles of non-animal origin, a hydrogel comprising water and a cellulose-derivative gelling agent, and polysorbate 80. Further described are methods of using the ready-to-use injectable compositions for reparative or plastic surgery, esthetic dermatology, facial contouring, body contouring, and gingival augmentation.
1 . A ready-to-use composition comprising:
(a) microspheres or microparticles of poly-L-lactic acid that are between 20 to 100 μm in size, wherein the poly-L-lactic acid is in an amount of 10 to 30 mg/mL, relative to the volume of the composition;
(b) a hydrogel comprising water and a carboxymethylcellulose in an amount of 1% to 3% by weight, relative to the weight of the composition;
(c) polysorbate 80 in an amount of about 0.5% to about 1.0% by weight, relative to the weight of the composition; and
(d) 10 mM phosphate buffer;
wherein the composition exhibits no foaming after shaking when observed at 20-22° C. after 1 day; and
wherein the ready-to-use composition is not reconstituted from a freeze-dried or lyophilized composition after storage and prior to administration.
2 . The composition of claim 1 , wherein the poly-L-lactic acid is in an amount of about 17 to about 18 mg/mL, relative to the volume of the composition.
3 . The composition of claim 1 , wherein the carboxymethylcellulose is in an amount of about 2% by weight, relative to the weight of the composition.
4 . The composition of claim 1 , wherein the polysorbate 80 occurs in an amount of 0.5% by weight, relative to the weight of the composition.
5 . The composition of claim 1 , wherein:
the is poly-L-lactic acid is present in an amount of 17 to 18 mg/mL, relative to the volume of the composition;
the carboxymethylcellulose is in an amount of 2% by weight, relative to the weight of the composition; and
the polysorbate 80 occurs in an amount of 0.5% by weight, relative to the weight of the composition.
6 . The composition of claim 1 , wherein the composition exhibits a viscosity between 5 to 45 mPas.
7 . The composition of claim 1 , wherein the ratio between the carboxymethylcellulose and the polysorbate 80 is between 6:1 to 1:1.
8 . The composition of claim 1 , wherein the composition further comprises a local anesthetic.
9 . The composition of claim 8 , wherein the local anesthetic is selected from the group consisting of: bupivacaine, butanilicaine, carticaine, cinchocaine, clibucaine, ethyl parapiperidinoacetylaminobenzoate, etidocaine, lignocaine, mepivacaine, oxethazaine, prilocaine, ropivacaine, tolycaine, trimecaine, vadocaine, articaine, levobupivacaine, amylocaine, cocaine, propanocaine, clormecaine, cyclomethycaine, proxymetacaine, amethocaine, benzocaine, butacaine, butoxycaine, butyl aminobenzoate, chloroprocaine, dimethocaine, oxybuprocaine, piperocaine, parethoxycaine, procaine, propoxycaine, and tricaine; and a combination thereof.
10 . The composition of claim 1 , wherein the composition is aseptic.
11 . The composition of claim 1 , wherein the composition further comprises sodium chloride and a pharmaceutically acceptable carrier.
12 . The composition of claim 11 , wherein the sodium chloride is present in a concentration of 0.9% w/v.
13 . A ready-to-use composition comprising:
(a) microspheres or microparticles of poly-L-lactic acid in an amount of 10 to 20 mg/mL, relative to the volume of the composition;
(b) a hydrogel comprising water and carboxymethylcellulose in an amount of about 160 to 180 mg/mL, relative to the volume of the composition;
(c) polysorbate 80, wherein the ratio of concentrations between carboxymethylcellulose and the polysorbate 80 is between about 3.6:1 to 1:1, and wherein the polysorbate-80 is present in an amount of about 0.5% to about 1.0% by weight; and
(d) 10 mM phosphate buffer;
wherein the composition exhibits no foaming after shaking when observed at 20-22° C. after 1 day;
wherein the ready-to-use composition is not reconstituted from a freeze-dried or lyophilized composition after storage and prior to administration.
14 . The composition of claim 13 , wherein the ratio of concentrations between the carboxymethylcellulose and the polysorbate 80 is between about 2:1 to 1:1.
15 . The composition of claim 13 , wherein the carboxymethylcellulose is in an amount of about 170 to 180 mg/mL, relative to the volume of the composition.
16 . The composition of claim 13 , wherein the poly-L-lactic acid is in an amount of about 15 to 20 mg/mL, relative to the volume of the composition.
17 . A ready-to-use composition comprising:
(a) microspheres or microparticles of poly-L-lactic acid that are between 20 to 100 μm in size, wherein the poly-L-lactic acid is in an amount of about 10 to about 40 mg/mL, relative to the volume of the composition;
(b) a hydrogel comprising water and carboxymethylcellulose in an amount of 1% to 3% by weight;
(c) polysorbate 80 in an amount of 0.5% to 1% by weight, relative to the weight of the composition; and
(d) 10 mM phosphate buffer;
wherein the composition exhibits no foaming after shaking when observed at 20-22° C. after 1 day; and
wherein the ready-to-use composition is not reconstituted from a freeze-dried or lyophilized composition after storage and prior to administration.
18 . The composition of claim 1 , wherein the composition exhibits a decreased rate of sedimentation by at least 5% relative to a control composition lacking the carboxymethylcellulose in an amount between 1% to 3% by weight, relative to the weight of the composition.
19 . The ready-to-use composition of claim 13 , wherein the composition exhibits a decreased rate of sedimentation by at least 5% relative to a control composition lacking the carboxymethylcellulose in an amount of about 160 to 180 mg/mL, relative to the volume of the composition.
20 . The ready-to-use composition of claim 17 , wherein the composition exhibits a decreased rate of sedimentation by at least 5% relative to a control composition lacking the carboxymethylcellulose in an amount of 1% to 3% by weight, relative to the weight of the composition.
21 . The composition of claim 1 , wherein the compositions exhibits no foaming after shaking when observed at 20-22° C. after about 4 hours.
22 . The ready-to-use composition of claim 13 , wherein the composition exhibits no foaming after shaking when observed at 20-22° C. after about 4 hours.
23 . The ready-to-use composition of claim 17 , wherein the compositions exhibits no foaming after shaking when observed at 20-22° C. after about 4 hours.
24 . A ready-to-use composition comprising:
(a) microspheres or microparticles of poly-L-lactic acid (PLLA) in an amount of about 18.75 mg/mL, relative to the volume of the composition;
(b) about 10 mM phosphate buffer;
(c) about polysorbate 80 in an amount of about 0.5% weight relative to the composition;
(d) carboxymethylcellulose in an amount of about 22.5 mg/mL, relative to the volume of the composition; and
(e) water;
wherein the composition is provided in a vial or pre-filled syringe, and is not reconstituted from a freeze-dried or lyophilized composition after storage and prior to administration; and
wherein the composition exhibits no foaming after shaking when observed at 20-22° C. after about 4 hours.
25 . The ready-to-use composition of claim 24 , wherein the composition comprises 150 mg of PLLA, 10 mM phosphate buffer, 0.5% polysorbate 80, 180 mg CMC, and 8 mL of water.
26 . The ready-to-use composition of claim 24 , wherein the composition comprises 150 mg of PLLA microparticles or microspheres, lidocaine, 10 mM phosphate buffer, 0.5% polysorbate 80, 180 mg CMC, and 8 mL of water.