Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
1997-07-11
2003-07-22
Peselev, Elli (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S171000
Reexamination Certificate
active
06596703
ABSTRACT:
FIELD OF INVENTION
This invention relates to the use of angiostatic steroids, which are known to have reduced or no systemic side effects typical of glucocorticoids, mineralocorticoids and sex steroids, for the promotion of angiogenesis and thus wound healing when used in combination with hyaluronan (for example hyaluronan and pharmaceutically acceptable salts thereof). This invention in one particular application may be used in creams, lotions, sprays, suppositories, and gels and the like for application in wound healing for delivery of for example an effective amount of tetrahydro steroids in combination with an effective amount of hyaluronic acid to the wound site, for example to treat incisions, burns, skin lesions, and ulcers. Equally appropriate applications would be administration of the invention intradermally, transdermally, intermuscularly, intramuscularly and intravenously when appropriate.
It is well documented that tetrahydro steroids such as tetrahydrocortisol (TH-F), tetrahydrocortisone (TH-E) and tetrahydrocortexolone (TH-S) are known not to possess the detrimental systemic side effects normally associated with glucocorticoids, mineralocorticoids and sex steroids since they do not bind to appropriate receptors such as do known glucocorticoids, mineralocorticoids and sex steroids. Typically, the continued use of glucocorticoids, mineralocorticoids and sex steroids for chronic ailments may result in a number of well known documented side effects such as bone wasting, fluid retention and infections. Therefore, these glucocorticoid steroids, mineralocorticoids and sex steroids are normally not recommended for a chronic program of treatment for patients. Thus for wound healing for chronic type wounds such as dermatitis, skin ulcers, hemorrhoids, and the like although they would benefit from the use of these aforementioned steroids, the expected systemic side effects would materialize.
The tetrahydra steroids are themselves angiostatic steroids. Other steroids are also angiostatic or anti-angiogenic steroids. They are known not to possess detrimental systemic side effects normally associated with glucocorticoids, mineralocorticoids and sex steroids. These angiostatic steroids have therefore very much reduced detrimental side effects (and in some instances are known not to possess these side effects). These angiostatic steroids are also normally associated with the inhibition of new blood vessel formation. For a discussion of the various research and use of angiostatic steroids, the reader is referred to the following listing of patents, patent applications and technical articles which are representative only and are not in any way implied to be an exhaustive listing. Throughout this disclosure, “angiostatic steroids” or the like are to be assumed to mean those steroids not possessing significant angiogenetic properties.
Title of
Country
Patent No.
Invention
Inventors
Assignee
US
4,771,042
Inhibition of
John M. Braughler;
The Upjohn
Angiogenesis
Edward D. Hall,
Company,
Involving the
both of Portage;
Kalamazoo,
Coadministra-
John M. McCall,
Mich.
tion of Steroids
Kalamazoo;
with Heparin or
Wendell Wierenga,
Heparin
Oshtemo Township,
Fragments
Kalamazoo County,
Mich.; Judah
Folkman, Brookline,
Mass.
US
4,975,537
Angiostatic
Paul A. Aristoff,
The Upjohn
Steroids
Portage; Harvey I.
Company,
Skulnick; Wendell
Kalamazoo,
Wierenga, both of
Mich.
Kalamazoo, all of
Mich.
US
5,336,767
Total or Partial
Francesco della
Fidia,
Esters of
Valle, Padova;
S.p.A.,
Hyaluronic
Aurelio Romeo,
Abano
Acid
Rome, both of Italy
Terme, Italy
US
5,506,354
Imidazolyl-
John M. McCall;
The Upjohn
piperazinyl
Donald E. Ayer,
Company,
Steroids
both of Kalamazoo;
Kalamazoo,
E. Jon Jacobsen,
Mich.
Plainwell; Frederick
J. VanDoornik,
Hamilton; John R.
Palmer; Harold A.
Karnes, both of
Kalamazoo, all of
Mich.
PCT
WO
Tetrahydro
Paul Aristoff,
The Upjohn
87/02672
Angiostatic
Harvey I. Skulnick,
Company
Steroids
Wendell Wierenga
PCT
WO
Topical Anti-
J. Holland,
The Upjohn
90/12577
Angiogenic as
Duane B.
Company
Hair Growth
Lakings
Inhibitors
PCT
WO
Suramin Type
Paul A. Aristoff,
The Upjohn
90/15816
Compounds
Mark A. Mitchell,
Company
and Angiostatic
John W. Wilks
Steroids to
Inhibit
Angiogenesis
PCT
WO
Steroids which
John Wilks, Thomas
The Upjohn
91/19731
Inhibit
Frank Dekoning,
Company
Angiogenesis
Paul Adrian
Aristoff
PCT
WO
Pharmaceutical
Alberto Perbellini,
94/17840
Compositions
Riccardo Gabriele
Comprising a
Ferretti, Franco
Spongy
Dorigatti, Lanfranco
Material
Callegro
Consisting of
Ester
Derivatives of
Hyaluronic
Acid Combined
with Other
Pharmaco-
logically
Active
Substances
EP
0 221 705
Tetrahydro
Paul A. Aristoff,
The Upjohn
Angiostatic
Harvey I. Skulnick,
Company
Steroids
Wendell Wierenga
Journal Articles
1. Opal Ka, C. J. et al.,
Synthesis
(1995): 766-8.
2. Cockerill, G. W. et al.,
International Review of Cytology
(1995) 159: 113-60.
3. Diaz-Flores, L. et al.,
Histology and Histopathology
(October 1994) 9(4): 807-43.
4. Sipos, E. P. et al,
Annals of the New York Academy of Sciences
(Sep. 6, 1994); 732: 263-72.
5. Thorpe, P. E. et al.,
Cancer Research
(Jul. 1, 1993) 53(13): 3000-7.
6. Folkman, J. and Ingber, D.,
Seminars in Cancer Biology
(April 1992) 3(2): 89-96.
7. Ribatti, D. et al.,
Haematologica
(July-August 1991) 76(4): 311-20.
8. Tobelem, G.,
Blood Coagulation and Fibrinolysis
(December 1990) 1(6): 703-5.
9. Wilks, J. W. et al.,
International Journal of Radiation Biology
, (July-August 1991) 60(1-2): 73-7.
10. Folkman, J. et al.,
Science
(Mar. 17, 1989) 243(4897): 1490-3.
11. Cariou, R. et al.,
Cell Biology International Reports
(December 1988) 12(12): 1037-47.
12. Folkman, J. and Ingber, D. E.,
Annals of Surgery
(September 1987) 206(3): 374-83.
13. Ingber, D. E. et al,
Endocrinology
(October 1986) 119(4): 1768-75.
14. Folkman, J.,
Cancer Research
(February 1986) 46(2): 467-73.
15. Crum, R. et al.,
Science
(Dec. 20, 1985) 230(4732): 1375-8.
16. Folkman, J.,
Pediatrics
(November 1984) 74(5): 850-6.
17. Blei, F. et al.,
Journal of Cellular Physiology
(June 1993) 155(3): 568-78.
18. Folkman, J. and Shing Y.,
Advances in Experimental Medicine and Biology
(1992) 313: 355-64.
19. Yamamoto, T., Terada, N., Nishizawa, Y. and Petrow, V.,
Angiostatic Activities of Medroxyprogesterone Acetate and its Analogues
(1994): 56, 393-399.
20. Colville-Nash, P., Alam, C., Appleton, I., Brown, J., Seed, M. and Willoughby, D.,
The Pharmacological Modulation of Angiogenesis in Chronic Granulomatous Inflammation
(1995) JPET 274: 1463-1472. Since wound healing depends on angiogenesis, (the reader is directed to article 3 above at page 811 for a discussion of angiogenesis) it would be desirable to induce angiogenesis utilizing safe compounds and which compounds do not have systemic side effects typical of glucocorticoids, mineralocorticoids and sex steroids, or at least substantially reduced side effects. However, the angiostatic steroids have not previously been recognized to stimulate new blood vessel growth. See for example, article 4 and page 265 therein. Specific reference is made to article 19 above to Nishizawa which verifies that angiostatic steroids do not bind glucocorticoid, mineralocorticoid and sex steroid receptors.
Applicants have in their PCT Application WO94/23725 published on Oct. 27, 1994 by Professor Willoughby et al., utilized an NSAID in combination with a form of hyaluronic acid for controlling, inhibiting, and/or regressing angiogenesis for the treatment of tumours and other diseases and conditions.
PCT Application WO94/17840 to Fidia published Aug. 18, 1994 discusses a spongy material consisting of total or partial ester derivatives of hyaluronic acid utilized for the administration of hyaluronic acid solutions to enhance the recovery of patients suffering from decubitus ulcers, wounds and burns. This document purports to describe the capability of hyaluronic acid to induce a rapid and complete tissue repair process. It is discussed further that anti-inflammatory agents may be contained in the solutions of hyaluronic acid. Specifically, the reference p
Alam Chandan
Seed Michael P.
Willoughby Derek A.
Jagotec AG
Leydig , Voit & Mayer, Ltd.
Peselev Elli
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