Repair of tissue in animals

Claim 2

A composition for the promotion of cell proliferation and tissue repair in animals whose active ingredients consist essentially of: - beta-type transforming growth factors (TGF-β); and - at least one activating agent present in an amount sufficient to activate said TGF-β, selected from the group consisting of epidermal growth factors (EGF) and alpha-type transforming growth factors (TGF-a), - which active ingredients are present in an amount sufficient to promote cell proliferation.

Claim 3

The composition of Claim 1, used for the topical promotion of fibroblast cell proliferation in mammals wherein the TGF-β and at least one activating agent are present in approximately equimolar amounts.

Claim 4

The composition of Claim 2, wherein said TGF-β is present in an amount of at least 1.0 nanogram per milliliter of composition.

Claim 5

The composition of Claim 3, wherein said TGF-β is present in an amount up to 1 milligram per milliliter of composition.

Claim 6

The composition of Claim 2, wherein the activating agent is an EGF.

Claim 7

The composition of Claim 2, wherein the activating agent is a TGF-a.

Claim 8

The composition of Claim 2 further containing at least one pharmaceutically acceptable carrier.

Claim 9

The composition of Claim 7, wherein the carrier is a purified collagen and the composition is a suspension for topical application.

Claim 10

The composition of Claim 7, wherein the carrier is a physiological saline solution and.the composition is an irrigant.

Claim 11

The composition of Claim 1, used for the systemic promotion of cell proliferation and tissue repair in manmals wherein the ZGF-β and at least one activating agent are present in approximately equimolar amounts and wherein the composition further contains a pharmaceutically acceptable carrier.

Claim 12

A method of treating mammalian topical wounds, burns, ulcers or other traumata comprising at least one topical application of the composition of Claim 2 in a pharmaceutically acceptable carrier. decubitus ulcers, and many other conditions, at present there is no practical way to accelerate wound healing with pharmacological agents. Although it is suggested in Tissue Growth Factors, supra, at p. 123 that EGF might be of benefit in this area, it has yet to be extensively used in a practical way for wound healing.

Claim 13

SUMMARY OF THE INVENTION

Claim 14

SUMMARY OF THE INVENTION

Claim 15

This invention affords compositions for the promotion of cell proliferation in animals, especially fibroblast cells in human beings. The compositions have as their active ingredients, beta-type transforming growth factor (TGF-a) and an activating agent. The activating agents of this invention are selected from at least one of epidermal growth factor (EGF) and alpha-type transforming growth factor (TGF-a).

Claim 16

This invention affords compositions for the promotion of cell proliferation in animals, especially fibroblast cells in human beings. The compositions have as their active ingredients, beta-type transforming growth factor (TGF-a) and an activating agent. The activating agents of this invention are selected from at least one of epidermal growth factor (EGF) and alpha-type transforming growth factor (TGF-a).

Claim 17

The TGF-B and the activating agent are preferably present in about equimolar amounts, and the active ingredients are present in an amount at least sufficient to stimulate cell proliferation (tissue repair).

Claim 18

The TGF-B and the activating agent are preferably present in about equimolar amounts, and the active ingredients are present in an amount at least sufficient to stimulate cell proliferation (tissue repair).

Claim 19

As another embodiment, the activated TGF-B compositions of this invention may be admixed with other (secondary) growth factors to enhance their activity.

Claim 20

As another embodiment, the activated TGF-B compositions of this invention may be admixed with other (secondary) growth factors to enhance their activity.

Claim 21

The compositions may be formulated in any suitable carrier for topical application, such as physiological saline solution or purified collagen suspension. The compositions also may be formulated in any suitable carrier for systemic administration.

Claim 22

The compositions may be formulated in any suitable carrier for topical application, such as physiological saline solution or purified collagen suspension. The compositions also may be formulated in any suitable carrier for systemic administration.

Claim 25

As a further embodiment, the compositions of this invention may be administered systemically by injection, enterally, transdermal patches, and the like, depending upon the nature and site of the traumata to be treated.

Claim 26

As a further embodiment, the compositions of this invention may be administered systemically by injection, enterally, transdermal patches, and the like, depending upon the nature and site of the traumata to be treated.

Claim 27

DETAILED DESCRIPTION OF_THE INVENTION

Claim 28

DETAILED DESCRIPTION OF_THE INVENTION

Claim 29

The term, "transforming growth factor" (T GF ) has been defined to include the set of polypeptides which confer the transformed phenotype on untransformed indicator cells. The transformed phenotype is operationally defined by the loss of density-dependent inhibition of growth in monolayer, overgrowth in monolayer, characteristic change in cellular morphology, and acquisition of anchorage independence, with the resultant ability to grow in soft agar. Untransformed, non-neoplastic cells will not form progressively growing colonies in soft agar, while the property of anchorage-independent growth of cells in culture has a particularly high correlation with neoplastic growth in vivo.

Claim 30

The term, "transforming growth factor" (T GF ) has been defined to include the set of polypeptides which confer the transformed phenotype on untransformed indicator cells. The transformed phenotype is operationally defined by the loss of density-dependent inhibition of growth in monolayer, overgrowth in monolayer, characteristic change in cellular morphology, and acquisition of anchorage independence, with the resultant ability to grow in soft agar. Untransformed, non-neoplastic cells will not form progressively growing colonies in soft agar, while the property of anchorage-independent growth of cells in culture has a particularly high correlation with neoplastic growth in vivo.

Claim 31

Although TGFs were first discovered in the conditioned medium of virally-transformed neoplastic mouse cells, the application of the acid/ethanol method for extraction of peptides from tissues has now shown that TGFs can be found in almost all tissues, both neoplastic and non-neoplastic, from all species of animals that have been examined thus far. Although TGF activity is usually measured with an in vitro phenotypic transformation assay, this does not imply that TGF

Claim 32

Although TGFs were first discovered in the conditioned medium of virally-transformed neoplastic mouse cells, the application of the acid/ethanol method for extraction of peptides from tissues has now shown that TGFs can be found in almost all tissues, both neoplastic and non-neoplastic, from all species of animals that have been examined thus far. Although TGF activity is usually measured with an in vitro phenotypic transformation assay, this does not imply that TGF

Claim 33

A transforming growth factor having an amino acid composition consisting essentially of the following residues per mole based upon an apparent molecular weight of 25,000: (wherein ND means not determined)

Claim 34

A transforming growth factor having an amino acid composition consisting essentially of the following residues per mole based upon an apparent molecular weight of 25,000: (wherein ND means not determined)

Claim 35

A transforming growth factor having a partial amino acid sequence as determined by - Edman Degredation consisting essentially of the following for each of its two subunits: where CMC is Half-cystine or cysteine, determined as S-carboxymethylcysteine.

Claim 36

A transforming growth factor having a partial amino acid sequence as determined by - Edman Degredation consisting essentially of the following for each of its two subunits: where CMC is Half-cystine or cysteine, determined as S-carboxymethylcysteine.

Claim 37

A method of treating mammalian topical wounds, burns, ulcers or other traumata comprising at least one topical application of the composition of Claim 23 in a pharmaceutically acceptable carrier.

Claim 38

A method of treating mammalian systemic traumata comprising at least one systemic administration of the composition of Claim 23 in a pharmaceutically acceptable carrier.