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Curcumin and curcuminoid inhibition of angiogenesis

a curcumin and curcumin technology, applied in the field of inhibition of angiogenesis, can solve the problems of limited effectiveness of current treatments for cancer and related diseases, numerous serious unintended effects, and interventions that may have serious unanticipated effects, and achieve the effects of inhibiting angiogenesis, reducing the risk of recurrence, and increasing the level of bfg

Inactive Publication Date: 2009-01-15
EMORY UNIVERSITY
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  • Description
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Benefits of technology

[0013]Methods for treating diseases or disorders of the skin which are characterized by angiogenesis have been developed using curcumin and curcumin analogs. Based on the results obtained with curcumin, it has been determined that other angiogenesis inhibitors can also be used to treat these skin disorders. It was also discovered that curcumin acts to inhibit angiogenesis in part by inhibition of basic fibroblast growth factor (bFGF), and thereby provides a means for treating other disorders characterized by elevated levels of bFGF, such as bladder cancer, using curcumin and other analogues which also inhibit bFGF.
[0014]Curcumin and demethoxycurcumin are the preferred agents for treating these disorders. The preferred means of administration is to apply the curcumin topically, for example, as an ointment or hydrogel containing between one-half percent (0.5%) and five percent (5%) of the curcumin, or regionally, orally to treat disorders of the gastrointestinal tract or by instillation, to treat bladder or cervical cancer. In alternative embodiments, the curcumin or its analogs can be implanted in the form of one or more pellets of a pharmaceutically acceptable vehicle encapsulating or encorporating the curcumin, or by one or more injections of a pharmaceutically acceptable aqueous solut...

Problems solved by technology

Current treatments of cancer and related diseases have limited effectiveness and numerous serious unintended effects.
Efforts continue to discover the origins of cancer at the genetic level, and correspondingly new treatments, but such interventions also may have serious unanticipated effects.
The metabolic and physiologic needs of mammalian cells are met by their proximity to capillaries, and limited resources may be diverted by imbalance of this supply system.
The mechanisms involved in angiogenesis are quite complicated, however, and no one appears to be the sole controlling mechanism.
Stimulation of angiogenesis in adult mammals, other than as a part of normal tissue repair, pregnancy or the menstrual cycle, is abnormal and often pathological.
Development of effective preventive and treatment means has been hampered by inadequate understanding of the factors controlling this process.

Method used

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  • Curcumin and curcuminoid inhibition of angiogenesis
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  • Curcumin and curcuminoid inhibition of angiogenesis

Examples

Experimental program
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Effect test

example 1

Curcumin Inhibition of Endothelial Cell Proliferation is Dependent on Curcumin Dose and the Presence or Absence of Basic Fibroblast Growth

[0076]Endothelial cells were stimulated to proliferate in the presence of 1 ng / ml bFGF. Curcumin was added in concentrations ranging from 0.5 to 10 μM to primary endothelial cells.

[0077]FIGS. 1A-C describe the effect of curcumin on endothelial cell proliferation in the absence of basic fibroblast growth factor (FGF; FIG. 1A), in the presence of bFGF (FIG. 1B) and in the absence of bFGF, where the endothelial cells have been transformed (FIG. 1C). A steep decrease in cell number was seen at 10 μM. No evidence of cytotoxicity was observed, and the number of cells at the end of treatment was not significantly less than the number cells originally plated. This decrease in proliferation due to curcumin concentration of 10 μM was observed in both the presence or absence of bFGF.

[0078]In addition, curcumin was able to inhibit the growth of endothelial ce...

example 2

Curcumin Inhibition of Corneal Neovascularization is Dependent on the Presence of Basic Fibroblast Growth Factor

[0079]The ability of curcumin to inhibit bFGF-induced corneal neovascularization in vivo was measured. Pellets were prepared containing 80 ng of bFGF and curcumin, or a control aromatic ketone, tetraphenylcyclopentadienone (TPCPD). TPCPD was added to rule out the possibility that the inhibition of neovascularization due to curcumin was not secondary to dilution. Neovascularization was assessed by slit lamp at 5 days after implantation, and the corneas were photographed.

[0080]FIGS. 2A-2B describe the effect of curcumin on the extent of bFGF-stimulated neovascularization in the mouse cornea (FIG. 2A), in relation to bFGF-stimulated neovascularization in the absence of curcumin (FIG. 2B). There was no difference in neovascularization in mice containing bFGF pellets in the presence or absence of TPCPD. Both the vessel length and sectpr sizes were significantly reduced in the p...

example 3

Curcumin and Other Curcumin Analog Inhibition of Corneal Neovascularization in the Presence of Basic Fibroblast Growth Factor is Dependent on the Dose and Structure of the Curcuminoid

[0081]Three curcumin analogs were assayed for their ability to inhibit bFGF-induced corneal neovascularization as described above.

[0082]FIGS. 3A and 3B describe the effect of curcumin and other curcuminoids, tetrahydrocurcumin, bisdemethoxycurcumin, and demethoxycurcumin, on corneal neovascularization, as measured by vessel length (FIG. 3A) and by sector size (FIG. 3B). All analogs showed inhibitory activity, with demethoxycurcumin showing the greatest activity on both sector size and vessel length, tetrahydrocurcumin having the least effect on sector size, and bisdemethoxycurcumin having the least effect on vessel length. All of the curcumin analogs showed significant inhibition of bFGF-mediated neovascularization compared with control pellets.

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Abstract

Methods for treating diseases or disorders of the skin which are characterized by angiogenesis have been developed using curcumin and curcumin analogs. Based on the results obtained with curcumin, it has been determined that other angiogenesis inhibitors can also be used to treat these skin disorders. It has further been discovered that curcumin acts to inhibit angiogenesis in part by inhibition of basic fibroblast growth factor (bFGF), and thereby provides a means for treating other disorders characterized by elevated levels of bFGF, such as bladder cancer, using curcumin and other analogues which also inhibit bFGF. Representative skin disorders to be treated include the malignant diseases angiosarcoma, hemangioendothelioma, basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Karposi's sarcoma, and the non-malignant diseases or conditions including psoriasis, lymphangiogenesis, hemangioma of childhood, Sturge-Weber syndrome, verruca vulgaris, neurofibromatosis, tuberous sclerosis, pyogenic granulomas, recessive dystrophic epidermolysis bullosa, venous ulcers, acne, rosacea, eczema, molluscum contagious, seborrheic keratosis, and actinic keratosis.

Description

[0001]The United States government has rights in this invention by virtue of grant R03 AR44947 from the National Institutes of Health.BACKGROUND OF THE INVENTION[0002]The invention is generally in the field of methods of inhibiting angiogenesis, and more specifically is drawn to methods and compositions for inhibiting angiogenesis.[0003]Current treatments of cancer and related diseases have limited effectiveness and numerous serious unintended effects. Based primarily on chemical, radiation and surgical therapy, these treatments have progressed only incrementally during more than thirty years of intensive research to discover the origins and devise improved therapies of neoplastic diseases.[0004]Current research strategies emphasize the search for effective therapeutic modes with less risk, including the use of natural products and biological agents. This change in emphasis has been stimulated by the fact that many of the consequences, to patients and their offspring, of conventiona...

Claims

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Application Information

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IPC IPC(8): A61K31/12A61P1/00A61K31/198A61K31/336A61K31/341A61K31/404A61K31/454
CPCA61K31/12A61K31/198A61K31/454A61K31/341A61K31/404A61K31/336A61P1/00
Inventor ARBISER, JACK L.
Owner EMORY UNIVERSITY
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