US5516533A
Expired / Lapsed
US
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Fluidized intestinal submucosa and its use as an injectable tissue graft
Assignee: Methodist Hospital
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Filing: 1994-11-22
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Granted: 1996-05-14
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Expires: 2014-11-22
Abstract
Abstract A fluidized, injectable tissue graft composition is described. The composition comprises comminuted intestinal submucosa or protease-digested intestinal submucosa. Methods for the preparation and use of injectable tissue graft compositions are described. In preferred embodiments the tissue graft material is prepared from the intestinal submucosa comprising the tunica submucosa, the muscularis mucosa and the stratum compactum of a segment of intestinal tissue of a warm-blooded vertebrate. Effective amounts of the fluidized graft compositions can be injected to promote repair tissue defects by inducing formation of endogenous tissues.
Inventors
- 👤 Stephen F. Badylak
- 👤 Robert J. Demeter
- 👤 Michael Hiles
- 👤 Sherry Voytik
- 👤 Peter M. Knapp, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 07:14
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/36; A61L27/3683; A61L27/3695; A61F; A61F2/00; A61F2/02; A61F2/28; A61K; A61K35/00; A61K35/12; A61K35/37; A61K35/38; A61L27/3604; A61L27/3629; A61L27/3641; A61L27/3645; A61L27/365; A61L27/367; A61L27/3691; A61P; A61P3/00; A61P43/00; A61F2002/2835; A61F2/30; A61F2002/30001; A61F2002/30003; A61F2002/3006; A61F2002/30062; A61F2002/30667; A61F2002/30677; A61F2210/00; A61F2210/0004; A61L2400/00; A61L2400/06
Claims Analysis
Total Claims: 39
Claim 1
Independent Claim
72 words
A method of preparing a tissue graft composition, said method comprising the steps of comminuting intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising intestinal submucosa delaminated from both the tunlea muscularis and at least the luminal portion of the tunica mucosa, and hydrating the resultant comminuted intestinal tissue to provide said tissue graft composition as a fluid having a viscosity of about 2 to about 300,000 cps at 25° C.
Claim 2
Independent Claim
72 words
A method of preparing a tissue graft composition, said method comprising the steps of comminuting intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising intestinal submucosa delaminated from both the tunlea muscularis and at least the luminal portion of the tunica mucosa, and hydrating the resultant comminuted intestinal tissue to provide said tissue graft composition as a fluid having a viscosity of about 2 to about 300,000 cps at 25° C.
Claim 3
Dependent Claim
23 words
The method of claim 1, wherein the comminuting step includes the step of freezing the intestinal tissue and grinding the frozen intestinal submucosa.
Claim 4
Dependent Claim
23 words
The method of claim 1 wherein the comminuting step includes the steps of freeze-drying the intestinal tissue and grinding the freeze-dried intestinal tissue.
Claim 5
Dependent Claim
22 words
The method of claim 1 wherein the comminuting step includes the step of processing the intestinal tissue in a high shear blender.
Claim 6
Dependent Claim
15 words
The method of claim 1 further comprising the step of sterilizing the tissue graft composition.
Claim 7
Dependent Claim
30 words
The method of claim 1 wherein the intestinal tissue consists essentially of the tunica submucosa and the basilar portion of the tunica mucosa of the intestine of a warm-blooded vertebrate.
Claim 8
Dependent Claim
39 words
The method of claim 1 further comprising the step of digesting the comminuted intestinal tissue with a protease for a period of time sufficient to solubilize said tissue to provide the tissue graft composition as a substantially homogeneous solution.
Claim 9
Dependent Claim
19 words
The method of claim 7, further comprising the step of neutralizing the substantially homogeneous solution to inactivate the protease.
Claim 10
Dependent Claim
30 words
The method of claim 7 wherein the intestinal tissue consists essentially of the tunica submucosa and the basilar portion of the tunica mucosa of the intestine of a warm-blooded vertebrate.
Claim 11
Dependent Claim
19 words
The method of claim 9, further comprising the step of separating the solubilized tissue from the substantially homogeneous solution.
Claim 12
Independent Claim
66 words
A method of preparing a tissue graft composition, said method comprising the step of digesting intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, in aqueous solution with a protease for a period of time sufficient to solubilize said intestinal tissue to form a substantially homogeneous solution.
Claim 13
Independent Claim
66 words
A method of preparing a tissue graft composition, said method comprising the step of digesting intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, in aqueous solution with a protease for a period of time sufficient to solubilize said intestinal tissue to form a substantially homogeneous solution.
Claim 14
Dependent Claim
19 words
The method of claim 11, further comprising the step of neutralizing the substantially homogeneous solution to inactivate the protease.
Claim 15
Dependent Claim
19 words
The method of claim 11, further comprising the step of separating the solubilized tissue from the substantially homogeneous solution.
Claim 16
Dependent Claim
33 words
The method of claim 11, wherein the intestinal tissue consists essentially of the tunica submucosa and a basilar portion of the tunica mucosa of a segment of small intestine of a warm-blooded vertebrate.
Claim 17
Dependent Claim
40 words
A composition comprising a suspension of comminuted intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising the tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, in an aqueous medium.
Claim 18
Dependent Claim
40 words
A composition comprising a suspension of comminuted intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising the tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, in an aqueous medium.
Claim 19
Dependent Claim
18 words
The composition of claim 15 having a viscosity of about 2 to about 300,000 cps at 25° C.
Claim 20
Dependent Claim
31 words
The composition of claim 15, wherein the intestinal tissue comprises the tunica submucosa and a basilar portion of the tunica mucosa of a segment of small intestine of a warm-blooded vertebrate.
Claim 21
Dependent Claim
38 words
A composition comprising protease digested intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising the tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, in an aqueous carrier.
Claim 22
Dependent Claim
38 words
A composition comprising protease digested intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising the tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, in an aqueous carrier.
Claim 23
Dependent Claim
18 words
The composition of claim 18 having a viscosity of about 2 to about 300,000 cps at 25° C.
Claim 24
Dependent Claim
31 words
The composition of claim 18, wherein the intestinal submucosa comprises the tunica submucosa and a basilar portion of the tunica mucosa of a segment of small intestine of a warm-blooded vertebrate.
Claim 25
Dependent Claim
13 words
The composition of claim 18, wherein the composition is substantially free of protease.
Claim 26
Independent Claim
101 words
A method of promoting wound healing comprising the step of applying to a wound in need of healing an effective amount of a tissue graft composition comprising a suspension of comminuted intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, in an aqueous medium or a solution of protease digested intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, in an aqueous carrier.
Claim 27
Independent Claim
101 words
A method of promoting wound healing comprising the step of applying to a wound in need of healing an effective amount of a tissue graft composition comprising a suspension of comminuted intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, in an aqueous medium or a solution of protease digested intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, in an aqueous carrier.
Claim 28
Dependent Claim
35 words
Dried intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, said tissue being in powder form.
Claim 29
Dependent Claim
35 words
Dried intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, said tissue being in powder form.
Claim 30
Dependent Claim
36 words
Dried protease-solubilized intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, said tissue being in powder form.
Claim 31
Dependent Claim
36 words
Dried protease-solubilized intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, said tissue being in powder form.
Claim 32
Independent Claim
88 words
A method for inducing the formation of endogenous tissue of a warm-blooded vertebrate in a locale at which formation of endogenous tissue is desired, said method comprising providing to the locale a tissue graft composition comprising a suspension of comminuted intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, or a protease digest of said intestinal tissue in an amount effective to induce endogenous tissue growth in the locale.
Claim 33
Independent Claim
88 words
A method for inducing the formation of endogenous tissue of a warm-blooded vertebrate in a locale at which formation of endogenous tissue is desired, said method comprising providing to the locale a tissue graft composition comprising a suspension of comminuted intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, or a protease digest of said intestinal tissue in an amount effective to induce endogenous tissue growth in the locale.
Claim 34
Dependent Claim
31 words
The method of claim 25 wherein the intestinal tissue comprises the tunica submucosa and a basilar portion of the tunica mucosa of a segment of small intestine of a warm-blooded vertebrate.
Claim 35
Dependent Claim
21 words
The method of claim 25 wherein the growth induced endogenous tissue is bone or connective tissue comprising collagen, elastin or muscle.
Claim 36
Dependent Claim
31 words
The method of claim 25 wherein the tissue graft composition is injected into tissue forming a sphincter in a warm-blooded mammal and the growth induced tissue is tissue forming the sphincter.
Claim 37
Independent Claim
71 words
A method of augmenting sphincter function in a warm-blooded mammal, the method comprising the step of injecting into tissue forming said sphincter an effective amount of a tissue graft composition comprising a suspension of comminuted intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, or a protease digest of said intestinal tissue.
Claim 38
Independent Claim
71 words
A method of augmenting sphincter function in a warm-blooded mammal, the method comprising the step of injecting into tissue forming said sphincter an effective amount of a tissue graft composition comprising a suspension of comminuted intestinal tissue of a warm-blooded vertebrate, said intestinal tissue comprising tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa, or a protease digest of said intestinal tissue.
Claim 39
Dependent Claim
51 words
The method of claim 29, wherein the intestinal tissue comprises the tunica submucosa and a basilar portion of the tunica mucosa of a segment of small intestine of a warm-blooded vertebrate, said intestinal tissue being delaminated from the tunica muscularis and the luminal portion of the tunica mucosa of said segment.
References Cited (Backward Citations)
US4902508A
Cited
US4956178A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-05-14 | 1999-11-13 | 2000-05-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-05-14 | 2003-11-13 | 2004-05-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-05-14 | 2007-11-13 | 2008-05-14 | $7700.00 | Window Closed / Lapsed |