Emulsions of Perfluorocarbons
The subject application provides for an emulsion comprising an amount of a perfluorocarbon liquid dispersed as particles within, a continuous liquid phase, wherein the dispersed particles have a monomodal particle size distribution and uses thereof. The subject application also provides for a method of manufacturing a perfluorocarbon emulsion, a process for preparing a pharmaceutical product containing a PFC emulsion and a process for validating a batch of an emulsion for pharmaceutical use.
1 . An emulsion comprising an amount of a perfluorocarbon liquid dispersed as particles within a continuous liquid phase, wherein the dispersed particles have a monomodal particle size distribution.
2 . The emulsion of claim 1 , containing less than 40 ppm residual fluoride by weight of the emulsion.
3 . The emulsion of claim 1 , containing less than 7 g/L lysophosphatidylcholine (LPTC or LPC) by weight of the emulsion.
4 . The emulsion of claim 1 , wherein 90% or more of the total amount by volume of the dispersed particles have a size of less than 700 nm.
5 . The emulsion of claim 1 , wherein 50% or more of the total amount by volume of the dispersed particles have a size of less than 400 nm.
6 . The emulsion of claim 1 , wherein the perfluorocarbon is perfluoro(tert-butylcyclohexane), perfluorodecalin, perfluoroisopropyldecalin, perfluoro-tripropylamine, perfluorotributylamine, perfluoro-methylcyclohexylpiperidine, perfluoro-octylbromide, perfluoro-decylbromide, perfluoro-dichlorooctane, perfluorohexane, dodecafluoropentane, or a mixture thereof.
7 . The emulsion of claim 1 , wherein the perfluorocarbon contains less than 5 ppm residual conjugated olefin by weight of the perfluorocarbon.
8 . The emulsion of claim 1 , wherein the perfluorocarbon contains less than 20 ppm residual organic hydrogen by weight of the perfluorocarbon.
9 . The emulsion of claim 1 , wherein the emulsion comprises 20-80% w/v perfluorocarbon.
10 . The emulsion of claim 1 , further comprising an emulsifier.
11 . The emulsion of claim 10 , comprising 1-10% w/v emulsifier.
12 - 20 . (canceled)
21 . The A method of increasing the firmness of the skin or reducing the appearance of fine lines, wrinkles or scars in a subject comprising topically administering to the skin of the subject the emulsion of claim 1 effective to increase the firmness of the subject's skin or reduce the appearance of fine lines, wrinkles or scars on the subject's skin.
22 . A method of manufacturing a perfluorocarbon emulsion comprising the steps:
a) mixing an emulsifier and aqueous medium together;
b) adding perfluorocarbon to the mixture of step a);
c) mixing the mixture of step b) to form a coarse emulsion;
d) obtaining a sample of the coarse emulsion of step c) and determining particle size distribution of the sample;
e) if the sample of step d) has a monomodal particle size distribution, then homogenizing the coarse emulsion of step c); and
f) obtaining the emulsion.
23 . The method of claim 22 , wherein in step e) the coarse emulsion of step c) is homogenized only if the median particle size of the sample of step d) is less than 20 μm.
24 . The method of claim 22 , wherein in step e) the coarse emulsion is homogenized at or above 7,000 psi.
25 . A process for preparing a pharmaceutical product containing a PFC emulsion, the process comprising:
a) obtaining a batch of perfluorocarbon emulsion or coarse emulsion;
b)1) determining the particle size distribution of the batch;
2) determining the total amount of residual fluoride present in the batch; or 3) determining the total amount of lysophosphatidylcholine (LPTC) present in the batch; and
c) preparing the pharmaceutical product from the batch only if 1) the batch is determined to have a monomodal particle size distribution; 2) the batch is determined to have less than 40 ppm residual fluoride by weight of the emulsion; or 3) the batch is determined to have less than 7 g/L lysophosphatidylcholine (LPTC) by weight of the emulsion.
26 . A process for validating a batch of an emulsion for pharmaceutical use, the process comprising:
a)1) determining the particle size distribution of a sample of the batch;
2) determining the total amount of residual fluoride in a sample of the batch; or 3) determining the total amount of lysophosphatidylcholine (LPTC) in a sample of the batch; and
b) validating the batch for pharmaceutical use only if 1) the sample of the batch has a monomodal particle size distribution; 2) the batch contains less than 40 ppm residual fluoride by weight of the emulsion; or 3) the batch contains less than 7 g/L lysophosphatidylcholine (LPTC) by weight of the emulsion.
27 . The process of claims 26 , wherein in steps a)1)-a)3) are performed after the sample of the batch has been subjected to stability testing.