JPWO2021154845A5

JPWO2021154845A5 -

Info

Publication number: JPWO2021154845A5
Application number: JP2022545858A
Authority: JP
Publication date: 2024-07-11

Claims

1. A self-assembling biopolymer for filling a tissue void or defect in a patient, comprising:
introducing the self-assembling biopolymer into a tissue void or defect;
and polymerizing the self-assembling biopolymer to form a shape-retaining matrix.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises an in situ polymerizable oligomeric collagen.

The self-assembling biopolymer of claim 2, wherein the in situ polymerizable oligomeric collagen comprises collagen molecules.

The self-assembling biopolymer of claim 3, wherein at least a portion of the collagen molecules are covalently linked by one or more intermolecular crosslinks.

The self-assembling biopolymer of claim 1, wherein the patient is a mammal.

The self-assembling biopolymer of claim 1, wherein the patient is a human.

The self-assembling biopolymer of claim 1, wherein the introducing is accomplished under sterile conditions.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises an in situ polymerizable collagen and the shape-retaining matrix comprises a collagen fibril matrix.

The self-assembling biopolymer of claim 8, wherein the self-assembling biopolymer comprises liquid type I collagen.

The self-assembling biopolymer of claim 8, wherein the self-assembling biopolymer comprises type I oligomeric collagen derived from porcine dermis.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises a solution containing lyophilized type I oligomeric collagen and an acid.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises a solution containing lyophilized type I oligomeric collagen and hydrochloric acid.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises a solution containing lyophilized type I oligomeric collagen and hydrochloric acid, the solution further comprising a buffer.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises an oligomeric collagen solution and a buffer, the oligomeric collagen solution comprising lyophilized type I oligomeric collagen and an acid.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises an oligomeric collagen solution and a buffer, the oligomeric collagen solution comprising lyophilized type I oligomeric collagen and an acid, and the ratio of oligomeric collagen solution to buffer is about 9:1.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises a solution containing lyophilized type I oligomeric collagen and 0.01 N hydrochloric acid, the solution having a concentration of about 8 mg/mL based on the dry weight of the lyophilized type I oligomeric collagen.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises a solution containing lyophilized type I oligomeric collagen and hydrochloric acid, the solution being clarified using ultracentrifugation.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises a solution containing lyophilized type I oligomeric collagen and hydrochloric acid, the solution being clarified using ultracentrifugation and then filtered through a sterile membrane filter.

The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises a solution containing lyophilized type I oligomeric collagen and hydrochloric acid, the solution being clarified using ultracentrifugation, irradiated with ultraviolet light, and then filtered through a sterile membrane filter.

10. The self-assembling biopolymer of claim 1, wherein the self-assembling biopolymer comprises a solution containing lyophilized type I oligomeric collagen and hydrochloric acid, which has been clarified using ultracentrifugation, irradiated with 500 mJ/ ^cm2 ultraviolet light, and then filtered through a sterile membrane filter.

The self-assembling biopolymer of claim 1, wherein introducing comprises injecting the self-assembling biopolymer into the tissue void or defect via a syringe.

The self-assembling biopolymer of claim 1, wherein the tissue void or defect is caused by a lumpectomy procedure.

The self-assembling biopolymer of claim 1, wherein the tissue void or defect is caused by a mastectomy procedure.

The self-assembling biopolymer of claim 1, wherein filling a tissue void or defect does not result in defect atrophy or scar tissue formation.

The self-assembling biopolymer of claim 1, wherein filling a tissue void or defect does not result in inflammatory mediators, an inflammatory response, or a foreign body reaction.

The self-assembling biopolymer of claim 1, wherein filling voids or defects in tissue results in a compression modulus or range of compression moduli substantially identical to that of native tissue.

The self-assembling biopolymer of claim 1, wherein filling the tissue voids or defects results in the production of breast tissue, including adipose tissue, mammary gland tissue, or a combination thereof.

The self-assembling biopolymer of claim 1, wherein the tissue implant response to filling tissue voids or defects is not adversely affected by irradiation, such that one or more of lipid cysts, microcalcifications, focal masses, and/or areas of high opacity are not observed.

1. An oligomeric collagen solution for filling a tissue void or defect in a patient, the tissue void or defect resulting from a lumpectomy or mastectomy procedure;
The oligomeric collagen solution is
introducing a mixture comprising an oligomeric collagen solution and a buffer into the tissue void or defect;
polymerizing the oligomeric collagen solution to form a collagen-fibrillar matrix;
1. An oligomeric collagen solution comprising freeze-dried type I oligomeric collagen and an acid.

The oligomeric collagen solution of claim 29, wherein the ratio of oligomeric collagen solution to buffer is about 9:1.

The oligomeric collagen solution of claim 29, wherein the acid comprises 0.01 N hydrochloric acid and the concentration of the oligomeric collagen solution is about 8 mg/mL based on the dry weight of the lyophilized type I oligomeric collagen.

1. An oligomeric collagen solution for filling a tissue void or defect in a patient, the tissue void or defect resulting from a lumpectomy or mastectomy procedure;
The oligomeric collagen solution is
introducing a mixture comprising an oligomeric collagen solution and a buffer into the tissue void or defect;
polymerizing the oligomeric collagen solution to form a collagen-fibrillar matrix;
The oligomeric collagen solution comprises lyophilized type I oligomeric collagen and 0.01 N hydrochloric acid;
The concentration of the oligomeric collagen solution is about 8 mg/mL based on the dry weight of lyophilized type I oligomeric collagen;
The oligomeric collagen solution, wherein the ratio of oligomeric collagen solution to buffer is about 9:1.

The oligomeric collagen solution of claim 32, wherein the oligomeric collagen solution has been clarified using ultracentrifugation, filtered through a sterile membrane filter, irradiated with ultraviolet light, or a combination thereof.

The oligomeric collagen solution of claim 32, wherein the tissue void or defect comprises a wound.

The oligomeric collagen solution of claim 32, wherein the tissue void or defect comprises a surgical wound.

The oligomeric collagen solution of claim 32, wherein the tissue void or defect results from tumor removal.

The oligomeric collagen solution of claim 32, wherein the tissue void or defect results from the removal of a breast tumor.

The oligomeric collagen solution of claim 32, wherein the self-assembling biopolymer comprises a tissue filler.

The oligomeric collagen solution of claim 32, wherein filling tissue voids or defects does not result in defect atrophy or scar tissue formation.

The oligomeric collagen solution of claim 32, wherein filling a tissue void or defect does not result in inflammatory mediators, an inflammatory response, or a foreign body reaction.

33. The oligomeric collagen solution of claim 32, wherein filling the tissue voids or defects results in a compression modulus or range of compression moduli substantially the same as that of native tissue.

The oligomeric collagen solution of claim 32, wherein filling the tissue voids or defects results in the production of breast tissue, including adipose tissue, glandular tissue, or a combination thereof.

33. The oligomeric collagen solution of claim 32, wherein the tissue implant response to filling tissue voids or defects is not adversely affected by irradiation, such that one or more of lipid cysts, microcalcifications, focal masses, and/or areas of high opacity are not observed.

1. An oligomeric collagen solution for filling a wound, comprising:
The oligomeric collagen solution is
introducing into the wound a mixture comprising an oligomeric collagen solution and a buffer;
polymerizing the oligomeric collagen solution to form a collagen-fibrillar matrix;
1. An oligomeric collagen solution, the oligomeric collagen solution comprising freeze-dried oligomeric collagen and an acid.

The oligomeric collagen solution of claim 44, wherein the freeze-dried type of oligomeric collagen comprises freeze-dried type I oligomeric collagen.

The oligomeric collagen solution of claim 44, wherein the wound comprises a surgical wound.

The oligomeric collagen solution of claim 46, wherein the surgical wound results from tumor removal.

The oligomeric collagen solution of claim 46, wherein the surgical wound results from removal of a breast tumor.

The oligomeric collagen solution of claim 44, wherein the oligomeric collagen solution comprises a tissue filler.

The oligomeric collagen solution of claim 44, wherein filling a wound does not result in defect atrophy and scar tissue formation.

The oligomeric collagen solution of claim 44, wherein filling the wound does not result in inflammatory mediators, an inflammatory response, or a foreign body reaction.

The oligomeric collagen solution of claim 44, wherein filling the wound results in a compression modulus or range of compression modulus substantially the same as that of native tissue.

The oligomeric collagen solution of claim 44, wherein filling the wound results in the production of breast tissue, including adipose tissue, glandular tissue, or a combination thereof.

The oligomeric collagen solution of claim 44, wherein the tissue implant response to filling the wound is not adversely affected by irradiation, such that one or more of lipid cysts, microcalcifications, focal masses, and/or areas of high opacity are not observed.

1. A self-assembling biopolymer for repairing and regenerating skeletal muscle tissue in a tissue void or defect in a patient, comprising:
The self-assembling biopolymer comprises:
introducing a self-assembling biopolymer into a tissue void or defect;
and polymerizing the self-assembling biopolymer to form a shape-retaining matrix.
Self-assembling biopolymers.

The self-assembling biopolymer of claim 55, wherein the tissue void or defect comprises a wound.

The self-assembling biopolymer of claim 55, wherein the tissue void or defect comprises a surgical wound.

The self-assembling biopolymer of claim 55, wherein the tissue void or defect results from tumor removal.

56. The self-assembling biopolymer of claim 55, wherein restoring and regenerating skeletal muscle tissue in tissue voids or defects does not result in defect atrophy or scar tissue formation.

56. The self-assembling biopolymer of claim 55, wherein restoring and regenerating skeletal muscle tissue in a tissue void or defect does not result in inflammatory mediators, an inflammatory response, or a foreign body reaction.

56. The self-assembling biopolymer of claim 55, wherein the restoration and regeneration of skeletal muscle tissue in tissue voids or defects results in a compression modulus or range of compression moduli substantially identical to that of native tissue.

The self-assembling biopolymer of claim 55, wherein restoring and regenerating skeletal muscle tissue in tissue voids or defects results in the production of skeletal muscle along with adipose tissue.

56. The self-assembling biopolymer of claim 55, wherein the tissue implant response to repair and regenerate skeletal muscle tissue is not adversely affected by irradiation, such that one or more of lipid cysts, microcalcifications, focal masses, and/or areas of high opacity are not observed.

1. An oligomeric collagen solution for repairing and regenerating skeletal muscle tissue in tissue voids or defects, comprising:
The oligomeric collagen solution is
introducing a mixture comprising an oligomeric collagen solution and a buffer into the tissue void or defect;
polymerizing the oligomeric collagen solution to form a collagen-fibrillar matrix;
1. An oligomeric collagen solution, the oligomeric collagen solution comprising lyophilized type I oligomeric collagen and an acid.

The oligomeric collagen solution of claim 64, wherein the tissue void or defect comprises a wound.

The oligomeric collagen solution of claim 64, wherein the tissue void or defect comprises a surgical wound.

The oligomeric collagen solution of claim 64, wherein the tissue void or defect results from tumor removal.

The oligomeric collagen solution of claim 64, wherein restoring and regenerating skeletal muscle tissue in tissue voids or defects does not result in defect atrophy or scar tissue formation.

The oligomeric collagen solution of claim 64, wherein restoring and regenerating skeletal muscle tissue in tissue voids or defects does not result in inflammatory mediators, inflammatory responses, or foreign body reactions.

The oligomeric collagen solution of claim 64, wherein the restoration and regeneration of skeletal muscle tissue in tissue voids or defects results in a compression modulus or range of compression modulus substantially identical to that of native tissue.

The oligomeric collagen solution of claim 64, wherein the restoration and regeneration of skeletal muscle tissue in tissue voids or defects results in the production of skeletal muscle along with adipose tissue.

The oligomeric collagen solution of claim 64, wherein the tissue implant response to repair and regenerate skeletal muscle tissue is not adversely affected by irradiation, such that one or more of lipid cysts, microcalcifications, focal masses, and/or areas of high opacity are not observed.

A collagen matrix prepared by introducing a self-assembling biopolymer into a tissue void or defect and polymerizing the self-assembling biopolymer to form a shape-retaining matrix, wherein the pH of the self-assembling biopolymer ranges from about 5.5 to about 8.5, the self-assembly time of the self-assembling biopolymer ranges from about 0.2 minutes to about 1.5 minutes, the shear storage modulus (G') of the collagen matrix ranges from about 2.0 kPa to about 4.0 kPa, the shear loss modulus (G") of the collagen matrix ranges from about 0.1 kPa to about 0.7 kPa, and the compressive modulus of the collagen matrix ranges from about 5.0 kPa to about 10.0 kPa.

74. The collagen matrix of claim 73, wherein the pH of the self-assembling biopolymer is about 7.25±about 0.25, the self-assembly time of the self-assembling biopolymer is about 0.8 minutes±about 0.3 minutes, the shear storage modulus (G') of the collagen matrix is about 3.1 kPa±about 0.4 kPa, the shear loss modulus (G") of the collagen matrix is about 0.4 kPa±about 0.1 kPa, and the compression modulus of the collagen matrix is about 7.7 kPa±about 1.9 kPa.

A kit for repairing and regenerating tissue in a tissue void or defect, comprising an in situ polymerizable collagen composition and a buffer.

The kit of claim 75, wherein the in situ polymerizable collagen composition comprises liquid type I collagen.

The kit of claim 75, wherein the in situ polymerizable collagen composition comprises type I oligomeric collagen derived from porcine dermis.

The kit of claim 75, wherein the in situ polymerizable collagen composition comprises a solution comprising lyophilized oligomeric collagen and an acid.

The kit of claim 75, wherein the in situ polymerizable collagen composition comprises a solution containing lyophilized type I oligomeric collagen and an acid.

The kit of claim 75, wherein the in situ polymerizable collagen composition comprises a solution containing lyophilized type I oligomeric collagen and hydrochloric acid.

76. The kit of claim 75, wherein the ratio of the in situ polymerizable collagen composition to buffer is about 9:1.

76. The kit of claim 75, wherein the in situ polymerizable collagen composition comprises a solution containing lyophilized type I oligomeric collagen and 0.01 N hydrochloric acid, and the concentration of collagen in the solution of the in situ polymerizable collagen composition is about 8 mg/mL based on the dry weight of the lyophilized type I oligomeric collagen.

76. The kit of claim 75, wherein the in situ polymerizable collagen composition comprises a solution comprising lyophilized type I oligomeric collagen and hydrochloric acid, and the solution of the in situ polymerizable collagen composition is clarified using ultracentrifugation.

76. The kit of claim 75, wherein the in situ polymerizable collagen composition comprises a solution comprising lyophilized type I oligomeric collagen and hydrochloric acid, and the solution of the in situ polymerizable collagen composition is clarified using ultracentrifugation and then filtered through a sterile membrane filter.

76. The kit of claim 75, wherein the in situ polymerizable collagen composition comprises a solution containing lyophilized type I oligomeric collagen and hydrochloric acid, and the solution of the in situ polymerizable collagen composition has been clarified using ultracentrifugation, irradiated with ultraviolet light, and then filtered through a sterile membrane filter.

76. The kit of claim 75, wherein the in situ polymerizable collagen composition comprises a solution comprising lyophilized type I oligomeric collagen and hydrochloric acid, and the solution of in situ polymerizable collagen composition has been clarified using ultracentrifugation, irradiated with 500 mJ/ ^cm2 ultraviolet light, and then filtered through a sterile membrane filter.

76. The kit of claim 75, further comprising a syringe configured to deliver a mixture of the in situ polymerizable collagen composition and a buffer solution to a void or defect in a tissue.

76. The kit of claim 75, wherein the buffer comprises about 0.03 mM to about 0.2 mM _MgCl2 .

76. The kit of claim 75, wherein the buffer comprises about 0.002 mM to about 0.02 mM _MgCl2 .

76. The kit of claim 75, wherein the buffer comprises less than about 0.02 mM _MgCl2 .

76. The kit of claim 75, wherein the buffer does not contain _MgCl2 .

76. The kit of claim 75, wherein the buffer further comprises about 0.003 M to about 0.03 _M _KH2PO4 .

76. The kit of claim 75, wherein the buffer further comprises about 0.01 M to about 0.1 _M _Na2HPO4 .

The kit of claim 75, wherein the buffer further comprises about 0.001 M to about 0.04 M KCl.

The kit of claim 75, wherein the buffer further comprises about 0.2 M to about 3.0 M NaCl.

The kit of claim 75, wherein the buffer further comprises about 0.02 N to about 0.2 N NaOH.

76. The kit of claim 75, wherein the buffer further comprises about 0.2 weight percent to about 5 weight percent glucose.

The kit of claim 75, wherein the buffer contains about 0.5 weight percent or less glucose.

The kit of claim 75, wherein the buffer does not contain glucose.

The kit of claim 75, wherein the concentration of collagen in the in situ polymerizable collagen composition is from about 0.1 mg/ml to about 40 mg/ml.

The kit of claim 75, wherein the concentration of collagen in the in situ polymerizable collagen composition is about 7 mg/mL to about 8 mg/mL.

The kit of claim 75, wherein the concentration of collagen in the neutralized collagen filler comprising the in situ polymerizable collagen composition and a buffer is about 6.3 to about 7.2 mg/mL.

The kit of claim 75, wherein the collagen solution comprises about 0.005N hydrochloric acid to about 0.1N hydrochloric acid.

76. The kit of claim 75, wherein the buffer is configured to polymerize the in situ polymerizable collagen composition in a single mixing step that includes mixing the in situ polymerizable collagen composition with the buffer.

The kit of claim 75, wherein the in situ polymerizable collagen composition and the buffer are in separate containers.

The kit of claim 105, wherein the individual containers comprise sterile vials.

The kit of claim 106, wherein the separate containers comprise separate compartments of a dual barrel syringe.

The kit of claim 107, wherein the dual barrel syringe includes a mixing element.

The kit according to claim 107, wherein the dual barrel syringe is sterile.

The kit of claim 75, further comprising instructions for using the components of the kit.

The kit of claim 75, further comprising at least one therapeutic agent configured for localized delivery to a tissue void or defect.

The kit of claim 111, wherein the at least one therapeutic agent comprises a chemotherapeutic agent, an anti-inflammatory agent, an antibiotic agent, an analgesic agent, or a combination thereof.

The kit of claim 75, wherein the tissue void or defect comprises a wound.

The kit of claim 75, wherein the tissue void or defect comprises a surgical wound.

The kit of claim 75, wherein the tissue void or defect results from removal of a tumor.

The kit of claim 75, wherein the tissue void or defect results from removal of a breast tumor.

The kit according to claim 75, for regenerating tissue after breast-conserving surgery.

The kit according to claim 75, for preparing a matrix in a tissue void or defect.

The kit of claim 78, wherein the in situ polymerizable collagen composition or the lyophilized oligomeric collagen is sterilized using ultraviolet radiation.

The kit of claim 119, wherein the collagen matrix obtained from the polymerization of the in situ polymerizable collagen composition maintains polymerization properties compared to a non-irradiated collagen composition or a non-irradiated lyophilized collagen, respectively.

The kit according to claim 119, wherein the polymerization property is a shear storage modulus.

The kit of claim 119, wherein the radiation dose ranges from about 5 mJ/ ^cm2 to about 800 mJ/ ^cm2 .

The kit of claim 119, wherein the radiation dose ranges from about 30 mJ/ ^cm2 to about 300 mJ/ ^cm2 .

The kit of claim 119, wherein the sterilization inactivates viruses.

The kit of claim 119, wherein the in situ polymerizable collagen composition or the lyophilized oligomeric collagen is sterilized using UVC irradiation.

The kit of claim 119, wherein the collagen composition or lyophilized oligomeric collagen is sterilized using UVC irradiation and sterile filtration.