Continued...
TABLE-US-00001 TABLE 1 Silicone Oil Compositions Example Ingredient Amount (weight %) 1 Silicone Oil (1000 cSt viscosity) 40% Low level cross-linked Hyaluronic 2% Acid (
HA) Sterile Water for Injection Approximately 58% (QS to make 100%) 2 Silicone Oil (1000 cSt viscosity) 20% Low level cross-linked
HA 2% Sterile Water for Injection Approximately 78% (QS to make 100%) 3 ADATO-SIL 5000 (5000 cSt 40% viscosity) Low level cross-linked
HA 2% Sterile Water for Injection Approximately 58% (QS to make 100%) 4 ADATO-SIL 5000 (5000 cSt 20% viscosity) Low level cross-linked
HA 2% Sterile Water for Injection Approximately 78% (QS to make 100%) 5 ADATO-SIL 5000 (5000 cSt 40% viscosity) Non-Crosslinked 2% Carboxymethylcellulose (CMC) Sterile Water for Injection Approximately 58% (QS to make 100%) 6 ADATO-SIL 5000 (5000 cSt 20% viscosity) Non-Crosslinked CMC 2% Sterile Water for Injection Approximately 78% (QS to make 100%) 7 Silicone Oil (12500 cSt viscosity) 40% Non-Crosslinked CMC 2% Sterile Water for Injection Approximately 58% (QS to make 100%) 8 Silicone Oil (12500 cSt viscosity) 20% Non-Crosslinked CMC 2% Sterile Water for Injection Approximately 78% (QS to make 100%) 9 Silicone Oil (12500 cSt viscosity) 40% Lactated Ringers Solution 29% Non-Crosslinked CMC 2% Sterile Water for Injection Approximately 29% (QS to make 100%) 10 Silicone Oil (12500 cSt viscosity 20% Lactated Ringers Solution 29% Non-Crosslinked CMC 2% Sterile Water for Injection Approximately 49% (QS to make 100%) 11 Silicone Oil (12500 cSt viscosity) 40% Lactated Ringers Solution 29% Low-level Crosslinked CMC 2% 1,4-Butanediol Diglycidyl Ether 0.1% (BDDE) Sterile Water for Injection Approximately 29% (QS to make 100%) 12 Silicone Oil (12500 cSt viscosity) 20% Lactated Ringers Solution 29% Low-level Crosslinked CMC 2% 1,4-Butanediol Diglycidyl Ether 0.1% (BDDE) Sterile Water for Injection Approximately 49% (QS to make 100%)
TABLE-US-00002 TABLE 2 Quantitative Results Pre- Post- Ex- Oil Cross- Treatment Treatment am- Viscosity Thick- linking of
Girth (cm)
Girth (cm) ple (cSt) ener Thickener
Flaccid Erect Flaccid Erect 1 1000
HA Low 9.5 11.4 11.4 13.3 2 1000
HA Low 9.5 11.4 10.8 12.7 3 5000
HA Low 10 12.7 12 14.6 4 5000
HA Low 9 10.8 10 12 5 5000 CMC None 9.5 11.4 10.5 13.3 6 5000 CMC None 10.8 13.3 12 14.6 7 12500 CMC None 10 12.7 12.7 15.2 8 12500 CMC None 10 12.7 12 14.6 9 12500 CMC None 9.5 11.4 12 14 10 12500 CMC None 9 10.8 10.8 12.7 11 12500 CMC Low 9 10.8 10.5 13.3 12 12500 CMC Low 10 12.7 12 14.6
TABLE-US-00003 TABLE 3 Qualitative Results Migration (Incidence of Incidence Ex- Incidence of Palpable Lumps of Skin am- Palpable Lumps on Pubic or Ulceration or ple on Shaft Scrotal Areas) Irritation
Girth Gain 1 High High High Good 2 High High Moderate Fair to Good 3 Low to Moderate Low to Moderate Low Good 4 Low to Moderate Low to Moderate Very Low Fair to Good 5 Low to Moderate Low to Moderate Low Good 6 Low to Moderate Low to Moderate Very Low Fair to Good 7 Very Low Very Low Very Low Very Good 8 Very Low Very Low Very Low Good 9 Very Low Very Low Very Low Very Good 10 Very Low Very Low Very Low Good 11 Rare Rare Rare Very Good 12 Rare Rare Rare Very Good
The data show that oils with increasing viscosities provided better clinical results with fewer side effects. More specifically, the trends observed using high viscosity 12500 cSt oil resulted in rare incidences of lumpiness (oil coalescence) and migration of the oil. Oils with high viscosity have reduced oil droplet coalescence, which prevents the formation of larger oil droplets and lumps, and significantly reduces the risk of migration.
The data also show that low level crosslinking of the thickener yields better results than non-crosslinked thickener. The best results were seen using a combination of high viscosity oil with a low level crosslinked thickener. CMC is inherently more difficult to break down by the human body than
HA (5-7 days vs. 48-72 hours respectively). Thus, non-crosslinked CMC is preferable to non-crosslinked
HA, but low cross-linked CMC is preferable to both.
While not tested, it is expected that the use of non-cross linked
HA would yield unacceptable clinical results due to prematurely dissolving, resulting in the increased risk of oil coalescence, lumpy formation, and greater migration into the pubic and scrotal areas.
Highly crosslinked
HA (e.g., as found in commercial products such as JUVEDERM and
Restylane) would be expected to dissolve too slowly to provide scaffolding for collagen growth in a reasonable time frame. This is particularly problematic for the penile enlargement patient for several reasons.
First, the patient will not wait up to 1.5 years for the collagen to be produced before resuming intercourse. Engaging in sexual intercourse before the collagen has completely formed will physically push the unconverted non-stable mixture into the pubic and or scrotal areas. Highly crosslinked
HA will unduly delay collagen formation, which will result in delaying the anchoring of collagen to the surrounding tissues causing instability and mobility of filler during physical duress.
Second, there is a high risk of imbalance and asymmetrical shape development due to long-term collagen production with an organ that expands, contracts, bends, etc., on a daily basis, increasing the shifting and movement of the filler material which in turn increases the risk of misshaping.
In addition, the use of a longer acting filler, such as JUVEDERM, in the volumes necessary for appreciable augmentation of the penile shaft, glans and/or scrotal areas, would result in an extended opportunity for large amounts of filler to migrate before being anchored by collagen formation. The risk of such longer acting fillers migrating into the pubic and or scrotal areas would be unacceptably high, essentially precluding the use of such fillers in large volumes. While it is theoretically possible to reduce the risk of large volume filler migration by injecting lesser amounts of longer acting fillers over an extended period of time, the number of procedures necessary to achieve an appreciable augmentation makes this method of treatment impractical and unappealing to patients.
The above composition and method variants of this example demonstrate that the compositions and methods of the present invention are useful for stimulating collagen production for
Male Enhancement. The compositions and methods of the present invention are also useful for, e.g., stimulating collagen production for face or body skin wrinkle reduction, smoothing cellulite, scar
Repair, hernia
Repair, and breast enhancement.
While the invention has been described in detail and with reference to specific examples thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof.
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