US5681561A
Expired / Lapsed
US
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Compositions and methods for improving autologous fat grafting
Assignee: Technion Research and Development Foundation Ltd
•
Filing: 1995-06-07
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Granted: 1997-10-28
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Expires: 2015-06-07
Abstract
Abstract The present invention relates to compositions and methods for enhancing the success of autologous fat grafting in a patient. The compositions according to the present invention are useful for enhancing autologous fat grafting by improving the survival rate of lipocytes which are injected into a patient as part of a fat grafting procedure. These compositions comprise a fat grafting effective amount of autologous lipocytes in combination with a lipocyte growth effective amount of a non-steroidal anabolic hormone selected from insulin, triiodothyronine/thyroxine (T 3 or T 4 ), mixtures thereof, and optionally, growth hormone, most preferably a mixture of all three hormones because of the favorable effect these three hormones exhibit in combination to promote autologous fat grafting, the hormones being further combined with a lipocyte growth effective amount of a nutrient medium, preferably a serum free nutrient medium as at least a minimum essential medium.
Inventors
- 👤 Bernard Hirshowitz
- 👤 Ella Lindenbaum
- 👤 Yaron Har-Shai
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 13:13
CPC Classifications
C; C12; C12N; C12N5/00; C12N5/06; C12N5/0602; C12N5/0652; C12N5/0653; A; A61; A61K; A61K31/00; A61K35/00; A61K35/12; A61K35/35; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/1808; A61K38/1841; A61K38/1858; A61K38/22; A61K38/28; A61K38/30; A61K45/00; A61K45/06
Claims Analysis
Total Claims: 52
Claim 1
Independent Claim
106 words
A composition for use in autologous fat grafting procedures comprising an adipocyte growth effective amount of at least one anabolic hormone selected from insulin, triiodothyronine, thyroxine or mixtures thereof in combination with a nutrient medium comprising adipocyte growth effective amounts of essential amino acids, a mixture of vitamins comprising effective amounts of folate, niacinamide, pantothenate, pyridoxine, riboflavin and thiamin, a mixture of inorganic ions selected from calcium, sodium, potassium, magnesium and chloride and glucose in aqueous solution, said composition further including a fat graft effective number of autologous adipocytes within the range of about 5×10 8 to about 5×10 12 cells per ml of said medium.
Claim 2
Dependent Claim
106 words
A composition for use in autologous fat grafting procedures comprising an adipocyte growth effective amount of at least one anabolic hormone selected from insulin, triiodothyronine, thyroxine or mixtures thereof in combination with a nutrient medium comprising adipocyte growth effective amounts of essential amino acids, a mixture of vitamins comprising effective amounts of folate, niacinamide, pantothenate, pyridoxine, riboflavin and thiamin, a mixture of inorganic ions selected from calcium, sodium, potassium, magnesium and chloride and glucose in aqueous solution, said composition further including a fat graft effective number of autologous adipocytes within the range of about 5×10 8 to about 5×10 12 cells per ml of said medium.
Claim 3
Dependent Claim
16 words
The composition according to claim 1 further including adipocyte growth effective amounts of non-essential amino acids.
Claim 4
Dependent Claim
23 words
The composition according to claim 2 wherein said anabolic hormone is insulin at a concentration of about 500 ng/ml to about 100 ug/ml.
Claim 5
Dependent Claim
22 words
The composition according to claim 3 wherein said insulin is included at a concentration of about 500 ng/ml to about 5 ug/ml.
Claim 6
Dependent Claim
11 words
The composition according to claim 3 further including triiodothyronine or thyroxine.
Claim 7
Dependent Claim
23 words
The composition according to claim 5 wherein said triiodothyronine is included in an amount ranging from about 1.0 ng/ml to about 50 ng/ml.
Claim 8
Dependent Claim
23 words
The composition according to claim 5 wherein said thyroxine is included in an amount ranging from about 5 ng/ml to about 100 ng/ml.
Claim 9
Dependent Claim
22 words
The composition according to claim 1 further including growth hormone in an amount ranging from about 0.5 ng/ml to about 50 ng/ml.
Claim 10
Dependent Claim
22 words
The composition according to claim 5 further including growth hormone in an amount ranging from about 0.5 ng/ml to about 50 ng/ml.
Claim 11
Dependent Claim
22 words
The composition according to claim 7 further including growth hormone in an amount ranging from about 0.5 ng/ml to about 50 ng/ml.
Claim 12
Dependent Claim
85 words
The composition according to claim 2 wherein said nutrient medium is selected from the group consisting of F10, F12, RPMI 1640, BGJ Medium, Dulbecco's Modified Essential Medium, Yamane, IMEM-20, Glasgow Modification Eagle Medium, L-15, McCoy's 5A Medium, Medium 199, Medium 199 with Earle's salt base, Medium 199 with Hank's salt base, CMRL 1415, CMRL 1969, CMRL 1066, NCTC 135, MB 75261, MAB 8713, DM 145, Williams'G, Neuman & Tytell, Higuchi, MCDB 301, MCDB 202, MCDB 501, MCDB 401, MCDB 411, MDBC 153 and MCDB 105.
Claim 13
Dependent Claim
85 words
The composition according to claim 8 wherein said nutrient medium is selected from the group consisting of F10, F12, RPMI 1640, BGJ Medium, Dulbecco's Modified Essential Medium, Yamane, IMEM-20, Glasgow Modification Eagle Medium, L-15, McCoy's 5A Medium, Medium 199, Medium 199 with Earle's salt base, Medium. 199 with Hank's salt base, CMRL 1415, CMRL 1969, CMRL 1066, NCTC 135, MB 75261, MAB 8713, DM 145, Williams'G, Neuman & Tytell, Higuchi, MCDB 301, MCDB 202, MCDB 501, MCDB 401, MCDB 411, MDBC 153 and MCDB 105.
Claim 14
Dependent Claim
41 words
The composition according to claim 2 further including an effective amount of a cellular growth factor or transforming factor selected from the group consisting of epithelial growth factor, transforming growth factor, platelet derived growth factor, insulin-like growth factor and mixtures, thereof.
Claim 15
Dependent Claim
170 words
A composition for use in autologous fat grafting procedures comprising an adipocyte growth effective amount of at least one anabolic hormone selected from insulin, triiodothyronine, thyroxine or mixtures thereof in combination with a nutrient medium selected from the group consisting of Minimum Essential Medium Eagle, F10, F12, RPMI 1640, BGJ Medium, Basal Medium Eagle, Dulbecco's Modified Eagle Medium, Minimum Essential Medium Eagle with Earle's salt base, Minimum Essential Medium Eagle with Hank's salt base, Minimum Essential Medium Eagle with non-essential amino acids, Yamane, IMEM-20, Glasgow Modification Eagle Medium, L-15, McCoy's 5A Medium, Medium 199, Medium 199 with Earle's salt base, Medium 199 with Hank's salt base, CMRL 1415, CMRL 1969, CMRL 1066, NCTC 135, MB 75261, MAB 8713, DM 145, Williams'G, Neuman & Tytell, Higuchi, MCDB 301, MCDB 202, MCDB 501, MCDB 401, MCDB 411, MDBC 153 and MCDB 105, said composition further including a fat graft effective number of autologous adiocytes within the range of about 5×10 8 to about 5 ×10 12 cells per ml of said medium.
Claim 16
Dependent Claim
170 words
A composition for use in autologous fat grafting procedures comprising an adipocyte growth effective amount of at least one anabolic hormone selected from insulin, triiodothyronine, thyroxine or mixtures thereof in combination with a nutrient medium selected from the group consisting of Minimum Essential Medium Eagle, F10, F12, RPMI 1640, BGJ Medium, Basal Medium Eagle, Dulbecco's Modified Eagle Medium, Minimum Essential Medium Eagle with Earle's salt base, Minimum Essential Medium Eagle with Hank's salt base, Minimum Essential Medium Eagle with non-essential amino acids, Yamane, IMEM-20, Glasgow Modification Eagle Medium, L-15, McCoy's 5A Medium, Medium 199, Medium 199 with Earle's salt base, Medium 199 with Hank's salt base, CMRL 1415, CMRL 1969, CMRL 1066, NCTC 135, MB 75261, MAB 8713, DM 145, Williams'G, Neuman & Tytell, Higuchi, MCDB 301, MCDB 202, MCDB 501, MCDB 401, MCDB 411, MDBC 153 and MCDB 105, said composition further including a fat graft effective number of autologous adiocytes within the range of about 5×10 8 to about 5 ×10 12 cells per ml of said medium.
Claim 17
Dependent Claim
23 words
The composition according to claim 14 wherein said anabolic hormone is insulin at a concentration of about 500 ng/ml to about 100 ug/ml.
Claim 18
Dependent Claim
11 words
The composition according to claim 15 further including triiodothyronine or thyroxine.
Claim 19
Dependent Claim
23 words
The composition according to claim 16 wherein said thyroxine is included in an amount ranging from about 5 ng/ml to about 100 ng/ml.
Claim 20
Dependent Claim
22 words
The composition according to claim 16 further including growth hormone in an amount ranging from about 0.5 ng/ml to about 50 ng/ml.
Claim 21
Independent Claim
98 words
A method for treating tissue depressions or augmenting tissue in patients comprising injecting into said tissue a composition comprising an adipocyte growth effective amount of at least one anabolic hormone selected from insulin, triiodothyronine, thyroxine or mixtures thereof in combination with a nutrient medium comprising lipocyte growth effective amounts of essential amino acids, a mixture of vitamins comprising effective amounts of folate, niacinamide, pantothenate, pyridoxine, riboflavin and thiamin, a mixture of inorganic ions selected from calcium, sodium, potassium, magnesium and chloride and glucose in aqueous solution, said composition further including a fat graft effective amount of autologous adipocytes.
Claim 22
Independent Claim
98 words
A method for treating tissue depressions or augmenting tissue in patients comprising injecting into said tissue a composition comprising an adipocyte growth effective amount of at least one anabolic hormone selected from insulin, triiodothyronine, thyroxine or mixtures thereof in combination with a nutrient medium comprising lipocyte growth effective amounts of essential amino acids, a mixture of vitamins comprising effective amounts of folate, niacinamide, pantothenate, pyridoxine, riboflavin and thiamin, a mixture of inorganic ions selected from calcium, sodium, potassium, magnesium and chloride and glucose in aqueous solution, said composition further including a fat graft effective amount of autologous adipocytes.
Claim 23
Dependent Claim
23 words
The method according to claim 19 wherein said anabolic hormone is insulin at a concentration of about 500 ng/ml to about 100 ug/ml.
Claim 24
Dependent Claim
22 words
The method according to claim 20 wherein said insulin is included at a concentration of about 500 ng/ml to about 5 ug/ml.
Claim 25
Dependent Claim
11 words
The method according to claim 20 further including triiodothyronine or thyroxine.
Claim 26
Dependent Claim
23 words
The method according to claim 22 wherein said triiodothyronine is included in an amount ranging from about 1.0 ng/ml to about 50 ng/ml.
Claim 27
Dependent Claim
23 words
The method according to claim 22 wherein said thyroxine is included in an amount ranging from about 5 ng/ml to about 100 ng/ml.
Claim 28
Dependent Claim
22 words
The method according to claim 19 further including growth hormone in an amount ranging from about 0.5 ng/ml to about 50 ng/ml.
Claim 29
Dependent Claim
22 words
The method according to claim 23 further including growth hormone in an amount ranging from about 0.5 ng/ml to about 50 ng/ml.
Claim 30
Dependent Claim
22 words
The method according to claim 24 further including growth hormone in an amount ranging from about 0.5 ng/ml to about 50 ng/ml.
Claim 31
Dependent Claim
120 words
The method according to claim 19 wherein said nutrient medium is selected from the group consisting of Minimum Essential Medium Eagle, Basal Medium Eagle, Dulbecco's Modified Eagle Medium, Minimum Essential Medium Eagle with Earle's salt base, Minimum Essential Medium Eagle with Hank's salt base, Minimum Essential Medium Eagle with non-essential amino acids, F10, F12, RPMI 1640, BGJ Medium, Dulbecco's Modified Essential Medium, Yamane, IMEM-20, Glasgow Modification Eagle Medium, L-15, McCoy's 5A Medium, Medium 199, Medium 199 with Earle's salt base, Medium 199 with Hank's salt base, CMRL 1415, CMRL 1969, CMRL 1066, NCTC 135, MB 75261, MAB 8713, DM 145, Williams'G, Neuman & Tytell, Higuchi, MCDB 301, MCDB 202, MCDB 501, MCDB 401, MCDB 411, MDBC 153 and MCDB 105.
Claim 32
Dependent Claim
120 words
The method according to claim 27 herein said nutrient medium is selected from the group consisting of Minimum Essential Medium Eagle, Basal Medium Eagle, Dulbecco's Modified Eagle Medium, Minimum Essential Medium Eagle with Earle's salt base, Minimum Essential Medium Eagle with Hank's salt base, Minimum Essential Medium Eagle with non-essential amino acids, F10, F12, RPMI 1640, BGJ Medium, Dulbecco's Modified Essential Medium, Yamane, IMEM-20, Glasgow Modification Eagle Medium, L-15, McCoy's 5A Medium, Medium 199, Medium 199 with Earle's salt base, Medium 199 with Hank's salt base, CMRL 1415, CMRL 1969, CMRL 1066, NCTC 135, MB 75261, MAB 8713, DM 145, Williams'G, Neuman & Tytell, Higuchi, MCDB 301, MCDB 202, MCDB 501, MCDB 401, MCDB 411, MDBC 153 and MCDB 105.
Claim 33
Dependent Claim
16 words
The method according to claim 29 wherein said nutrient medium is MCDB 105 or BJG medium.
Claim 34
Dependent Claim
25 words
The method according to claim 27 wherein said adipocytes are substantially separated from triglycerides, cell fragments, blood components, blood cells and large connective tissue fragments.
Claim 35
Dependent Claim
43 words
The method according to claim 19 further including an adipocyte growth effective amount of a cellular growth factor or transforming factor selected from the group consisting of epithelial growth factor, transforming growth factor, platelet derived growth factor, insulin-like growth factor and mixture, thereof.
Claim 36
Independent Claim
122 words
A method for improving the engrafting of fat in an autologous fat graft procedure comprising utilizing in said fat graft procedure a composition comprising an adipocyte growth effective amount of at least one non-steroidal anabolic hormone selected from insulin, triiodothyronine, thyroxine or mixtures thereof, in combination with a nutrient medium comprising adipocyte growth effective amounts of essential amino acids, a mixture of vitamins comprising effective amounts of folate, niacinamide, pantothenate, pyridoxine, riboflavin and thiamin, a mixture of inorganic ions selected from calcium, sodium, potassium, magnesium and chloride and glucose in aqueous solution, said composition further including a fat graft effective amount of autologous adipocytes, said lipocytes being substantially separated from triglycerides, cell fragments, blood components, blood cells and large connective tissue fragments.
Claim 37
Independent Claim
122 words
A method for improving the engrafting of fat in an autologous fat graft procedure comprising utilizing in said fat graft procedure a composition comprising an adipocyte growth effective amount of at least one non-steroidal anabolic hormone selected from insulin, triiodothyronine, thyroxine or mixtures thereof, in combination with a nutrient medium comprising adipocyte growth effective amounts of essential amino acids, a mixture of vitamins comprising effective amounts of folate, niacinamide, pantothenate, pyridoxine, riboflavin and thiamin, a mixture of inorganic ions selected from calcium, sodium, potassium, magnesium and chloride and glucose in aqueous solution, said composition further including a fat graft effective amount of autologous adipocytes, said lipocytes being substantially separated from triglycerides, cell fragments, blood components, blood cells and large connective tissue fragments.
Claim 38
Dependent Claim
20 words
The method according to claim 33 wherein said composition further comprises an adipocyte growth effective amount of non-essential amino acids.
Claim 39
Dependent Claim
23 words
The method according to claim 34 wherein said anabolic hormone is insulin at a concentration of about 500 ng/ml to about 100 ug/ml.
Claim 40
Dependent Claim
22 words
The method according to claim 35 wherein said insulin is included at a concentration of about 500 ng/ml to about 5 ug/ml.
Claim 41
Dependent Claim
35 words
The method according to claim 35 further including triiodothyronine in an amount ranging from about 1.0 ng/ml to about 50 ng/ml or thyroxine in an amount ranging from about 5 ng/ml to about 100 ng/ml.
Claim 42
Dependent Claim
22 words
The method according to claim 34 further including growth hormone in an amount ranging from about 0.5 ng/ml to about 50 ng/ml.
Claim 43
Dependent Claim
22 words
The method according to claim 37 further including growth hormone in an amount ranging from about 0.5 ng/ml to about 50 ng/ml.
Claim 44
Dependent Claim
119 words
The method according to claim 33 wherein said nutrient medium is selected from the group consisting of Minimum Essential Medium Eagle, Basal Medium Eagle, Dulbecco's Modified Eagle Medium, Minimum Essential Medium Eagle with Earle's salt base, Minimum Essential Medium Eagle with Hank's salt base, Minimum Essential Medium Eagle with non-essential amino acids, F10, F12, RPMI 1640, BGJ Medium, Dulbecco's Modified Essential Medium, Yamane, IMEM-20, Glasgow Modification Eagle Medium, L-15, McCoy's 5A Medium, Medium 199, Medium 199 with Earle's salt base, Medium 199 with Hank's salt base, CMRL 1415, CMRL1969, CMRL 1066, NCTC 135, MB 75261, MAB 8713, DM 145, Williams'G, Neuman & Tytell, Higuchi, MCDB 301, MCDB 202, MCDB 501, MCDB 401, MCDB 411, MDBC 153 and MCDB 105.
Claim 45
Dependent Claim
120 words
The method according to claim 39 wherein said nutrient medium is selected from the group consisting of Minimum Essential Medium Eagle, Basal Medium Eagle, Dulbecco's Modified Eagle Medium, Minimum Essential Medium Eagle with Earle's salt base, Minimum Essential Medium Eagle with Hank's salt base, Minimum Essential Medium Eagle with non-essential amino acids, F10, F12, RPMI 1640, BGJ Medium, Dulbecco's Modified Essential Medium, Yamane, IMEM-20, Glasgow Modification Eagle Medium, L-15, McCoy's 5A Medium, Medium 199, Medium 199 with Earle's salt base, Medium 199 with Hank's salt base, CMRL 1415, CMRL 1969, CMRL 1066, NCTC 135, MB 75261, MAB 8713, DM 145, Williams'G, Neuman & Tytell, Higuchi, MCDB 301, MCDB 202, MCDB 501, MCDB 401, MCDB 411, MDBC 153 and MCDB 105.
Claim 46
Dependent Claim
16 words
The method according to claim 41 wherein said nutrient medium is MCDB 105 or BJG medium.
Claim 47
Dependent Claim
43 words
The method according to claim 33 further including an adipocyte growth effective amount of a cellular growth factor or transforming factor selected from the group consisting of epithelial growth factor, transforming growth factor, platelet derived growth factor, insulin-like growth factor and mixtures thereof.
Claim 48
Independent Claim
122 words
A method for improving the engrafting of fat in an autologous fat graft procedure comprising utilizing in said fat graft procedure a composition comprising an adipocyte growth effective amount of a combination of insulin, human growth hormone and triiodothyronine or thyroxine in combination with a nutrient medium comprising adipocyte growth effective amounts of essential amino acids, non-essential amino acids, a mixture of vitamins comprising effective amounts of folate, niacinamide, pantothenate, pyridoxine, riboflavin and thiamin, a mixture of inorganic ions selected from calcium, sodium, potassium, magnesium and chloride and glucose in aqueous solution, said composition further including a fat graft effective amount of autologous adipocytes, said adipocytes being substantially separated from triglycerides, cell fragments, blood components, blood cells and large connective tissue fragments.
Claim 49
Independent Claim
122 words
A method for improving the engrafting of fat in an autologous fat graft procedure comprising utilizing in said fat graft procedure a composition comprising an adipocyte growth effective amount of a combination of insulin, human growth hormone and triiodothyronine or thyroxine in combination with a nutrient medium comprising adipocyte growth effective amounts of essential amino acids, non-essential amino acids, a mixture of vitamins comprising effective amounts of folate, niacinamide, pantothenate, pyridoxine, riboflavin and thiamin, a mixture of inorganic ions selected from calcium, sodium, potassium, magnesium and chloride and glucose in aqueous solution, said composition further including a fat graft effective amount of autologous adipocytes, said adipocytes being substantially separated from triglycerides, cell fragments, blood components, blood cells and large connective tissue fragments.
Claim 50
Dependent Claim
68 words
The method according to claim 44 wherein said insulin is included in said composition at a concentration ranging from about 500 ng/ml to about 100 ug/ml, said growth hormone is included in said composition at a concentration ranging from about 0.5 ng/ml to aobut 50 ng/ml and said triidothyronine or thyroxine is included in said composition at a concentration ranging from about 1.0 ng/ml to about 100 ng/ml.
Claim 51
Dependent Claim
84 words
The method according to claim 45 wherein said medium is selected from the group consisting of F10, F12, RPMI 1640, BGJ Medium, Dulbecco's Modified Essential Medium, Yamane, IMEM-20, Glasgow Modification Eagle Medium, L-15, McCoy's 5A Medium, Medium 199, Medium 199 with Earle's salt base, Medium 199 with Hank's salt base, CMRL 1415, CMRL 1969, CMRL 1066, NCTC 135, MB 75261, MAB 8713, DM 145, Williams'G, Neuman & Tytell, Higuchi, MCDB 301, MCDB 202, MCDB 501, MCDB 401, MCDB 411, MDBC 153 and MCDB 105.
Claim 52
Dependent Claim
16 words
The method according to claim 44 wherein said nutrient medium is MCDB 105 or BJG medium.
References Cited (Backward Citations)
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