Compositions and methods for soft tissue augmentation
Inventors
Niklason, Laura • Li, Yuling • Blum, Juliana • Dahl, Shannon • Erickson, Geoffrey • Zeigler, Frank
Assignees
Publication Number
US-8198245-B2
Publication Date
2012-06-12
Expiration Date
2028-07-24
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Abstract
The present invention provides compositions comprising isolated human collagen, isolated human elastin and a pharmaceutically acceptable carrier wherein the human elastin is substantially insoluble in water with a molecular weight greater than 100 kDa. The present invention further provides methods and kits for soft tissue augmentation.
Core Innovation
The invention provides compositions comprising isolated human collagen, isolated human elastin, and a pharmaceutically acceptable carrier, wherein the human elastin is substantially insoluble in water with a molecular weight greater than 100 kDa. These compositions are designed for soft tissue augmentation, including dermal and subdermal applications, and can include additional components such as glycosaminoglycans, active agents, cells, or tissues to enhance tissue repair and volume.
The problem addressed by the invention stems from drawbacks of existing injectable tissue bulking agents. Synthetic materials like silicone, oils, and waxes have healing complications and are viscous and difficult to inject. Animal-derived materials such as bovine collagen and hyaluronic acid from rooster combs cause immune reactions or have non-human origins, resulting in inflammation or limited persistence in vivo. Existing elastin preparations often induce calcification upon implantation, limiting their safety and efficacy.
The invention solves these problems by providing highly pure extracellular matrix components derived from human vascular tissues cultured and decellularized to remove cellular components, reducing immunogenicity and inflammation. The compositions combine isolated human collagen with cross-linked, insoluble human elastin of high molecular weight, thus mimicking native skin extracellular matrix more closely and improving longevity, tissue integration, and elasticity. The elastin isolated by this method does not induce calcification in vivo, addressing a critical limitation of prior art elastin formulations.
Claims Coverage
The patent contains one independent composition claim, and additional claims addressing filler compositions, kits, and method features related to the compositions. The main inventive features focus on the preparation and characteristics of isolated human elastin and its combination with collagen for soft tissue augmentation.
Injectable composition comprising isolated human elastin from non-frozen human vascular tissue processed by decellularization, strong base, and primary alcohol treatment
An injectable composition comprising isolated human elastin and a pharmaceutically acceptable carrier in solution, where the elastin is isolated from human vascular tissue which has not been frozen, by decellularizing the vascular tissue, exposing it to a strong base, and subsequently to a primary alcohol, and wherein the elastin is substantially insoluble in water with a molecular weight greater than 100 kDa.
Cross-linked human elastin
The isolated human elastin in the composition is cross-linked.
Concentration ranges of isolated human elastin
The composition comprises about 2 to about 60 mg/ml, preferably about 3 to 30 mg/ml, of isolated human elastin.
Inclusion of isolated human glycosaminoglycans and cells
The composition may further include isolated human glycosaminoglycans, adipose tissue, or dermal fibroblasts.
Incorporation of one or more active agents
The composition may further include active agents selected from anti-inflammatory agents, tissue formation agents, adipose tissue formation agents, anesthetics, antioxidants, heparin, growth factors, connective tissue activating peptides, tumor necrosis factors, interleukins, colony stimulating factors, erythropoietin, nerve growth factors, interferons, or combinations thereof.
Dermal or subdermal filler comprising the composition
A dermal or subdermal filler comprising the composition containing the isolated human elastin and pharmaceutically acceptable carrier as described.
Non-calcifying elastin in vivo
The elastin in the composition does not induce calcification in vivo in a human.
Kit for soft tissue augmentation
A kit comprising the injectable composition, a syringe, and a sterile wrapper providing a sterile environment, optionally including agents such as heparin, growth factors, peptides, and other biologically active molecules.
Specific reagents for elastin isolation
The strong base used to treat the decellularized tissue is NaOH, and the primary alcohol used is ethanol.
Human vascular tissue source
The human vascular tissue used for elastin isolation is human aorta.
Compositions comprising both isolated human collagen and elastin
The composition further includes isolated human collagen in mixture with isolated human elastin and the pharmaceutically acceptable carrier, where the collagen is isolated from micro-bead culture, has a molecular weight of about 100 to 500 kDa, and is present at about 10-100 mg/ml, preferably about 30 mg/ml.
Overall, the claims cover injectable compositions comprising highly purified isolated human elastin obtained by a specific decellularization and chemical treatment method from human aorta tissue, with defined molecular weight and solubility properties, cross-linking, optionally combined with isolated human collagen and other agents, used for soft tissue augmentation, including filler products and kits.
Stated Advantages
The compositions comprising human-derived extracellular matrix components reduce immune reaction and inflammation compared to animal-derived materials.
The combination of collagen and elastin mimics native human skin extracellular matrix more closely, improving elasticity, tissue augmentation, and persistence in vivo.
Isolated human elastin does not induce calcification in vivo, overcoming a significant limitation of existing elastin preparations.
Deriving materials from engineered and decellularized human vascular tissue results in highly pure products with reduced potential for adverse tissue reactions.
Documented Applications
Soft tissue augmentation including dermal and subdermal fillers to treat lines, folds, wrinkles, minor facial depressions, cleft lips, deformities due to aging or disease, vocal cord or glottis deformities, lip deformities, crow's feet, and orbital grooves around the eye.
Augmentation of tissue volume in areas such as the face, breast, chin, cheek, and nose, including correction of indentations due to injury, surgery, acne, scars, radiation damage, or trauma.
Filling indentations or volume loss in pelvic floor tissue, peri-urethral area, neck of the urinary bladder, or junction of the urinary bladder and ureter.
Use of kits comprising compositions and syringes to perform soft tissue augmentation.
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