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Injectable microfoam containing a sclerosing agent |
| RE40640 |
Injectable microfoam containing a sclerosing agent
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| Patent Drawings: | |
| Inventor: |
Garrido, et al. |
| Date Issued: |
February 17, 2009 |
| Application: |
10/941,013 |
| Filed: |
September 15, 2004 |
| Inventors: |
Garrido; Juan Cabrera (Granada, ES)
Garcia-Olmedo; Juan Cabrera (Granada, ES)
|
| Assignee: |
BTG International Ltd. (London, GB) |
| Primary Examiner: |
Ghali; Isis |
| Assistant Examiner: |
|
| Attorney Or Agent: |
Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P. |
| U.S. Class: |
424/423; 424/422; 424/484; 424/489; 514/706; 514/708; 514/709; 514/945 |
| Field Of Search: |
424/423; 424/422; 424/489; 424/484 |
| International Class: |
A61F 2/00 |
| U.S Patent Documents: |
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| Foreign Patent Documents: |
1 232 837; 3417182; 0 054 728; 0 077 752; 0 123 235; 0 131 540; 0 217 582; 0 324 938; 0 359 246; 0 656 203; 0 997 396; 2 672 038; 2 775 436; WO 92/05806; 94/21384; WO 95/00120; WO 96/25194; WO 99/43371; WO 00/24649; WO 00/66274; WO 00 72821 |
| Other References: |
German Nullity Action Complaint filed Jul. 27, 2001 and translation into English. cited by other.
German Nullity Action First Brief filed Dec. 3, 2001 and translation into English. cited by other.
German Nullity Action Supplemental Brief filed Dec. 31, 2002 and translation into English. cited by other.
German Nullity Action Kreusler Brief filed Jan. 27, 2003 and translation into English. cited by other.
German Nullity Action Decision by German Court in English dated Feb. 4, 2003. cited by other.
German Nullity Action English Translation of the Substantiation of Appeal to the Federal Court of Justice on Sep. 26, 2003. cited by other.
German Nullity Action English Translation of the Reply to appeal dated Feb. 12, 2004. cited by other.
K1--Von P. Flockiger, "Nicht-operative retrograde Varicenverodung mit Varsylschaum", Schweizerische Medizinische Wochenschrift, No. 48, pp. 1368-1370, (1956) with English translation. cited by other.
K2--H. Mayer et al., "On the aetiology and treatment of varices of the lower extremities", Angiology, Chirurgische Praxis, pp. 521-528, (1957) with English translation. cited by other.
K3--Meyer's Encyclopedia, 5.sup.th Edition, vol. 15, pp. 386 (1895) with English translation. cited by other.
K5--Dr. Med. Jo{umlaut over (z)}e Baridevic; "Varicosclerozation in Phlebological Practice", The Journal for Doctors, in Clinic and Practice; XXI Volume No. 3, pp. 126-136; Jan. 11, 1989, and translation into English. cited by other.
K6--W. Gillesberger; "The Equipment of the Dermatologist Working in the Field of Phlebology", the Journal for Skin Diseases; vol. 44 (18), pp. 669-674; 1969 and translation into English. cited by other.
K7--Dr. E. Lunkenhelmer; letter to Chem. Fabrik Kreussler & Co.; Mar. 20, 1967 and translation into English. cited by other.
K8--Gianni Belcaro; "Mirco-sclerotherapy"; Sclerotherapy in Venous Disease; pp. 89-95; 2002. cited by other.
K9--M. Schadeck; "Ultrasound-controlled Sclerotherapy of the Great Saphenous Veins"; Phlebologie; vol. 46, No. 4, pp. 673-682, 1993 and translation into English. cited by other.
K10--E. Rabe et al.; "Guidelines to Sclerosing Treatment of Varicose Veins"; Leitlinien der DGP, Phlebologie; vol. 6, pp. 154-158; 2001 and translation into English. cited by other.
K12--K. Sigg, "Newer Aspects of the Techinque of Treating Varicosities", Therapeutishce Umschau, vol. 6, pp. 127-134, 1949 and translation into English. cited by other.
K13--M. Schadeck; "Duplex Controlled Sclerosing Treatment of the Great Saphenous Vein"; Phlebol; vol. 25, pp. 78-92; 1996 and translation into English. cited by other.
K14--R. Rowden-Foote; "Varicose Veins Hemorrhoids Other Conditions--Their Treatment by Injection"; London, H.K. Lewis & Co. Ltd.; pp. 13-45, 106-119; 1944. cited by other.
K15--A. Rae; "The Treatment of Varicose Veins with Etamolin Foam"; Acta Dermato-Venereologica; vol. 39, pp. 428-432, 1959. cited by other.
K16--E.J. Orbach et al.; "The Thrombogenic Property of Foam of a Synthetic Anionic Detergent (Sodium Tetradecyl Sulfate N.N.R.)", Angiol 1, pp. 237-243; 1950. cited by other.
K17--M.D.H.-D. Bock; "Varicosis and its Therapy", Arzttiche Praxis; XIX Volume, No. 60, pp. 2146-2148; Jul. 29, 1967 and translation into English. cited by other.
K18--O. Henschel;"Die Varizenverordening--Verordungstherapie mit Aethoxysklerol--Kreussler"; p. 22; 1968 and translation into English. cited by other.
K21--J. Orbach, "Sclerotherapy of Varicose Veins", American Journal of Surgery, vol. LXVI, No. 3, pp. 362-366, Dec. 1944. cited by other.
K22--J.R. Cabrera Garrido et al., "Extending the Limits of Sclerotherapy: New Sclerosing Products", Phlepp;pgoe, vol. 50, No. 2, pp. 181-188;997. cited by other.
K23--J. Cabrera; "Application Techniques for Sclerosant in Micro-Foam Form"; pp. 39-44. cited by other.
K24--Video (VHS) tape of Compression Sclerotherapy, H.R., Bernbach, M.D. and English Translation of the Documentation Accompanying the Video K24; pp. 1-16. cited by other.
K25--Dr. J.C. Wollmann et al.; Evaluation of the Test; Kreussler Pharma; pp. 17-28, Jan. 29, 2003. cited by other.
DVD #1 and #2 containing video clips shown during interview of Jan. 7, 2004. cited by other.
Written commentary tracking the DVDs submitted with Supplemental Information Disclosure Statement of Mar. 24, 2004. cited by other.
Meyer's Encyclopedia, 5.sub.th Edition, 1895, vol. 15, pp. 386. cited by other.
R. Bayeux, "Comparative Resistance of Dog and Rabbit to Intravenous Injection of Oxygen", Compt. Rend. vol. 156, pp. 1329-1331, 1913, with Abstract in English. cited by other.
F.W. Tunnicliffe et al., "The Intravenous Injection of Oxygen Gas as a Therapeutic Measure", Lancet, vol. II, pp. 321-323, 1916, with Abstract in English. cited by other.
G. Galata, "Intravenous Injection of Oxygen in Dogs", Archivio di Fisiologia, vol. 21, pp. 331-350, 1923, with Abstract in English. cited by other.
L. Moszkowiez, "Treatment of Varicose Veins with Sugar Injections, combined with vein ligation", Zentralblatt fur Chirurgie, No. 28, pp. 1731-1736, 1927 and translation into English. cited by other.
G. de Takats, "Ambulatory Ligation of the Saphenous Vein", The Journal of the American Medical Association, vol. 94, No. 16, pp. 1194-1197, Apr. 19, 1930. cited by other.
G. de Takats et al., "The Injection Treatment of Varicose Veins", Surgery, Gynecology and Obstetrics, vol. L., No. 3, pp. 545-561, Mar. 1930. cited by other.
De L'Academie des Sciences, Conformement A Une Decision de L'Academie, pp. 890-892, Jan. 1930 and translation into English. cited by other.
I.S. Tunick et al., "Sodium Morrhuate as a Sclerosing Agent in the Treatment of Varicose Veins", Annals of Surgery, vol. XCV, pp. 734-737, 1932. cited by other.
H. Jausion, "Glycerine Chromee et Sclerose des Ectasies Veineuses", La Presse Medicale, No. 53, pp. 1061-1063, Jul. 5, 1933. cited by other.
H. Harkins et al., "Embolism by Air and Oxygen: Comparative Studies", Proceedings of the Society for Experimental Biology and Medicine, vol. 32, pp. 178-181, 1934-35. cited by other.
L. Ferguson, "Ligation of Varicose Veins, Ambulatory Treatment Preliminary To Sclerosing Injections", Annals of Surgery, vol. CII, pp. 304-314, 1935. cited by other.
A. Ochsner et al., "Comparative Value of Intravenous Sclerosing Substances", Archives of Surgery, vol. 29, No. 3, pp. 397-416, Sep. 1934. cited by other.
H. Biegeleisen, "Fatty Acid Solutions for the Injection Treatment of Varicose Veins", Annals of Surgery, vol. CV, pp. 610-615, 1937. cited by other.
A. Schmier, "Clinical Comparison of Sclerosing Solutions in Injection Treatment of Varicose Veins, Delayed Slough: Recurrence of Varices", The American Journal of Surgery, vol. XXXVI, No. 1, pp. 389-397, Apr. 1937. cited by other.
R.M. Moore et al., "Injections of Air and Carbon Dioxide into a Pulmonary Vein", Annals of Surgery, vol. 112, pp. 212-218, 1940. cited by other.
W. Heyerdale et al., "Management of Varicose Veins of the Lower Extremities", Annals of Surgery, vol. 114, pp. 1042-1049, 1941. cited by other.
R. Rowden-Foote; "Varicose Veins Hemorrhoids and Other Conditions--Their Treatment by Injection"; London, H.K. Lewis & Co. Ltd.; pp. 13-45, 106-119; 1944. cited by other.
E.J. Orbach; "Sclerotherapy of Varicose Veins--Utilization of and Intravenous Air Block"; American Journal of Surgery; vol. LXVI, No. 3, pp. 362-366, Dec. 1944. cited by other.
E.J. Orbach, "Scleotherapy of Varicose Veins", American Journal of Surgery, vol. LXVI, No. 3, pp. 362-366, Dec. 1944. cited by other.
R.E. Weston et al., "The Influence of Denitrogenation on the Response of Anesthetized Dogs to Intravenously Injected Oxygen", vol. 26, pp. 837-848, 1946. cited by other.
L. Reiner, "The Activity of Anionic Surface Active Compounds in Producing Vascular Obliteration", Surface Active Sclerosing Agents, Proceedings of the Society for Experimental Biology and Medicine, vol. 62, pp. 49-54, May-Jun. 1946. cited by other.
R. Zingg, "Experimental tests with the new sclerosing agent Geigy", pp. 1-9, 1948. cited by other.
R. Foote, "Treatment", Varicose Veins, Chapter 5, p. 65 and 86, 1949. cited by other.
K. Sigg. "Newer Aspects of the Technique of Treating Varicosities", Therapeutishce Umschau, vol. 6, pp. 127-134, 1949 and translation into English. cited by other.
R. Jung, "Injection Treatment of Varicose Veins", Praxis, pp. 195-198, 1950 and translation into English. cited by other.
E.J. Orbach, "Contributions to the Therapy of the Varicose Complex", Journal of the International College of Surgeons, pp. 765-771, Jun. 1950. cited by other.
H. Rogge, "On the dangers of sclerosing recurring varicose veins", Deutsche Medizinische Wochenschrift, No. 9, p. 301, 1950 and translation into English. cited by other.
E.J. Orbach et al.; "The Thrombogenic Property of Foam of a Synthetic Anionic Detergent (Sodium Tetradecyl Sulfate N.N.R.)", Angiol 1, pp. 237-243; 1950. cited by other.
Sigg, "Regarding treatment of varicose veins and their complications", Dermatologica, vol. 100, p. 317, 1950 and translation into English. cited by other.
G. de Takats et al., "Division of the Popliteal Vein In Deep Venous Insufficiency of the Lower Extremities", Society for Vascular Surgery Issue, vol. 29, No. 3, pp. 342-354, Mar. 1951. cited by other.
R.S. Handley, "The Treatment of Varicose Veins", The Practitioner--Diseases of the Veins, No. 993, vol. 166, pp. 228-235, Mar. 1951. cited by other.
H.E. Lockhart-Mummery et al., "Varicose Ulcer--A Study of the Deep Veins with Special Reference to Retrograde Venography", The British Journal of Surgery, vol. XXXVIII, No. 151, pp. 284-295, Jan. 1951. cited by other.
E. Orbach, "Leg Ulcers of Vascular Origin and Their Therapy" The Americian Journal of Surgery, vol. LXXXI, No. 5, pp. 568-572, May 1951. cited by other.
M. Battezzati et al., "Treatment of Lower Limb Varices with Multiple Endermic Ligations and Sclerosant Injections Combined or not with Stripping of the long Saphenous Vein's higher region", Minerva Chirurgica, pp. 936-939, 1952 and translation intoEnglish. cited by other.
H. Leonhardt, "On the Treatment of Extensive Formation of Varicose Veins with Ligature of the v. Saphena and Varicoid Injection Through Distally Inserted Ureteral Catheter", Arztliche Wochenschrift, vol. 7, No. 3, pp. 56-58, Jan. 1952 andtranslation into English. cited by other.
G. Mayer, "The Treatment of Varicose Veins from the point of View of Sclerotherapy, in particularly on the Basis of Varicophtine", Munchener Medizinische Woohenschrift, vol. 16, No. 20, Columns 1037-1039, Jan. 1952 and translation into English.cited by other.
H.G. Oden, "Can the Results of the Treatment of Varicose Vains and Ulcus Cruris be Improved?", Munchener, Medizinische Wochenschrift, vol. 22, No. 8, pp. 364, Jan. 1952 and translation into English. cited by other.
P. Piutaches et al., "Pathogenic Considerations on Varicose Veins Developed in Pregnancy", Lyon Chirurigical, Bulletin offical de la Socirte de Chriurgie de Lyon, vol. 47, No. 3, pp. 263-278, Apr. 1952 and translation into English. cited by other.
P. Jaeger, "The Current Treatment Standard for Crural Ulcer and Varices", Deutsche Medizinische Wochenschrift, vol. 77, No. 14, pp. 421-425, Apr. 4, 1952 and translation into English. cited by other.
K. Sligg, "The Treatment of Varicosities and Accompanying Complications", Angiology, The Journal of Vascular Diseases, vol. 3, No. 5, pp. 355-379, Oct. 1952. cited by other.
H. Wefers et al., "Results of Injection Treatment with Regard to Extreme Varication", Zentralblatt for Chirugie, Issue No. 43, pp. 1825-1828, 1952 and translation into English. cited by other.
K. Sigg, "The Foamed Rubber Compression for Phlebitis and for Phlebitic and Varicose Complications", Die Medizinische, No. 27-28, pp. 910-915, Jul. 1952 and translation into English. cited by other.
P. Piulachs et al., "Pathogenic Study of Varicose Veins", Angiology, The Journal of Vascular Diseases, vol. 4, No. 1, pp. 59-100, Feb. 1953. cited by other.
F. Kunkel, "Medical Journal of Munich", 95.sup.th year of edition, vol. 30, No. 44, p. 53 1953 and translation into English. cited by other.
Vons Hans Brucke et al., "The combined foam sclerosis of varices", Wiener Medizinische Wochenschrift, vol. 104, No. 1, pp. 111-113, Jan. 1954 and translation into English. cited by other.
G. de Takats et al., "Aneurysms: General Considerations", Angiology, The Journal of Vascular Disease, vol. 5, No. 3, pp. 173-208, Jun. 1954. cited by other.
A. Hauser et al., "Prophylaxis of Phlebitis and Treatment of Varices During Pregnancy", Schweizerische Medizinische Wochenschrift, 84.sup.th year, No. 1, pp. 13-14, Jan. 2, 1954 and translation into English. cited by other.
G.D. Lilly et al., "An Evaluation of "High" Lumbar Sympathectomy in Arteriosclerotic Circulatory Insufficiency of the Lower Extremities", Surgery, Original Communications, vol. 35, No. 1, pp. 40-44, Jan. 1954. cited by other.
Maarz, "Nil nocerel: Life-Threatening anaphylactic Incidents in Connection with Sclerosing of Varicose Veins", Munchener Medizinische Wochenschrift, vol. 27, No. 35, 1954. cited by other.
E.J. Orbach, "Allergenic Tissue Reaction of Catgut, an Aid for the Obliteration of Varicose Veins", The Journal of the International College of Surgeons, vol. XXII, No. 6, pp. 707-710, Dec. 1954. cited by other.
H. Leidinger, Sclerosation with air-block technique (Varicocid plus Varicocid foam), Medizinische Klinik, pp. 1183-1184, 1954 and translation into English. cited by other.
J and P Vacheron, "Essential Varicose Veins on Lower Limbs: Sclerosant Treatment by Streaming", Archives of Cardio-Vascular Diseases, 7.sup.th Year, No. 12, pp. 1033-1038, Dec. 1954 and translation into English. cited by other.
A. Ree, "Varicose Vein Treatment with Foam of Etamolin", Dansk Laegeforening, No. 12-15, pp. 452-453, Jun. 1955 and translation into English. cited by other.
A. Hobner, "Der Chirurg, Journal for All Fields of Surgical Medicine", 26.sup.th Year of Edition, 1955 with translation into English. cited by other.
H. Dodd, "The `Stripping` Operation for Varicose Veins", The Postgraduate Medical Journal, vol. 31, pp. 73-78, 1955. cited by other.
F. Jaeger, "Primary or Secondary Varicose Veins", Die Medizinische, No. 36, pp. 1237-1340, Sep. 1955 and translation into English. cited by other.
W. Leun et al., "The Limits and Risks of the Sclerotherapy of Varicose Veins", German Medical Weekly Journal, No. 7, pp. 257-260, Feb. 18, 1955 and translation into English. cited by other.
F. Schurcher, "For the Practice Varicose Veins and Deep Chronic Crural Thrombosis", Munchener Medizinische Wochenschrift, No. 41, pp. 1354-1358, Oct. 14, 1955 and translation into English. cited by other.
K. Sigg. "The Treatment of Leg Ulcers", Die Medizinische, No. 17, pp. 646-648, 1955 and translation into English. cited by other.
K. Sigg, "Therapeutic Issues--On the Treatment of Vein Thrombosis with Butazolidin", Schwetzerische Medizinische Wochenschrift, 65.sup.th year of the edition, No. 11, pp. 261-262, Mar. 12, 1955 and translation into English. cited by other.
M.H. Steinberg, "Evaluation of Sotradecol in Sclerotherapy of Varicose Veins", Angiology The Journal of Vascular Diseases, vol. 6, No. 6, pp. 519-532, Dec. 1955. cited by other.
Fluckinger, P., Brugg, "Non-Surgical Retrograde Sclerosis of Varicose Veins With Varsyl Foam," Schweizerische Medizinische Wochenschrift No. 48, pp. 1368-1370, 1956 and translation into English. cited by other.
R.W. Decoppet, "The Sclerotherapy of Varices with Thrombophilic Patients", Swiss Medical Weekly Journal, 86.sup.th year, No. 20, pp. 509-513, May 19, 1956 and translation into English. cited by other.
R. May, "Impairments and Risks of the Treatment of Varicose Veins", Munchener Medizinische Wochenschrift, No. 1, pp. 13-16, Jan. 1956 and translation into English. cited by other.
E. Rappert, "The Therapy of Varicose Crural Ulcers", Wiender Medizinische Wochenschrift, vol. 106, No. 48, pp. 999-1000, Dec. 1, 1956 and translation into English. cited by other.
K. Sigg, "Varicose Veins and Deep Seated Chronic Leg Vein Thrombosis" Munchener Medizinische Wochenschrift, vol. 98, No. 8, pp. 260-263, Feb. 1956. cited by other.
M.J. Oppenheimer et al., "In vivo Visualization of Intracardiac Structures with Gaseous Carbon Dioxide--Cardiovascular-Respiratory Effects and Associated Changes in Blood Chemistry", American Journal of Physiology, vol. 186, pp. 325-334, Jul.-Sep.1956. cited by other.
K. Sigg, "Treatment of Superfical and Deep Thrombosis and the Application of Butazolidine", Gynaecologia, Supplementum and vol. 144, pp. 19-23, Jul. 2 to 4, 1956. cited by other.
K. Sigg, "A Good Prophylaxis of Thrombosis during Pregnancy, delivery and childbed as well as for Operations can Prevent the Thrombo-Embolism", Munchener Medizinische Wochenschrift, vol. 99, No. 17, p. 581 and 610-613 Apr. 1957 and translation intoEnglish. cited by other.
H. Mayer et al., "Angiology: The Aetiology and Treatment of Varicosities of the Lower Extremity," Chirurgische Praxis, pp. 521-528, 1957 and translation into English. cited by other.
T. Durant, et al., "The Safety of Intravascular Catbion Dioxide and its Use for Roentgenologic Visualization of Intracardiac Structures", Annals of Internal Medicine, vol. 47, No. 2, pp. 191-201, Aug. 1957. cited by other.
R.R. Foote, "Varicose Vein Problems in General Practice", The Practitioner--Medical Etiquette, vol. 179, No. 179, pp. 59-66, Jul. 1957. cited by other.
E.J. Orbach, "Reappraisal of the Sclerotherapy of Varicose Veins", Angiology--The Journal of Vascular Diseases, vol. 8, No. 6, pp. 520-527, Dec. 1957. cited by other.
E. Rappert, "The treatment of varicose veins following a phlebitis and thrombosis", Winer Medizinische Wochenschrift, No. 4, pp. 100-101, 1957 and translation into English. cited by other.
G. Savonuzzi et al., "A Therapeutic Method that Combines Sclerosing Agents and Anticoagulants for varicose diseases of the lower limb", Minerva Medical, vol. XLVIII, No. 24, pp. 1124-1126, Mar. 24, 1957 and translation into English. cited by other.
Von H. Westhues et al., "The Varicose Symptom Complex", Medizinsche Klinik, No. 16, pp. 657-660, 1957, and translation into English. cited by other.
H. Willenegger et al., "Attempt at carrying out Thromboembolism Propylaxis without Anticoagulants", Schweizerische Medizinische Wochenschrift--Journal Suisse de Medecine, vol. 87, Supplement for No. 24, pp. 739-748, 1957 and translation intoEnglish. cited by other.
K. Sigg, "New Approaches to the Treatment of Thrombosis", Angiology--The Journal of Vascular Diseases, vol. 8, No. 1, pp. 44-59, Feb. 1957. cited by other.
K. Sigg et al., "Prophylaxis of Thrombosis during Gravidity", Die Medizinische, No. 12, pp. 420-423, Jan. 1957 and translation into English. cited by other.
F. Jaeger, "Varcose Veins", Deutsche Medizinische Wochenschrift, vol. 83, No. 30, p. 1295, Jul. 1958, and translation into English. cited by other.
K. Sigg, "Prevention and Treatment of Thromboembolic Complications", Wiener Medizinische Wochenschrift, No. 10, pp. 206-213, Mar. 1958, and translation into English. cited by other.
E. Rappert, "The achievements of surgical therapy of varicose veins and leg ulcers?", Die Medizinische, No. 22, pp. 906-914, May 1958, and translation into English. cited by other.
E.J. Orbach, "Has Injection Treatment of Varicose Veins Become Obsolete?", The Journal of American Medical Association, vol. 166, No. 16, pp. 1964-1968, Apr. 19, 1958. cited by other.
A Lemaire et al., "Effect of Intra-arterial oxygen injection on blood cholesterol", Therapie, vol. 13, pp. 395-399, 1958, with Abstract in English. cited by other.
A. Ree; "The Treatment of Varicose Veins with Etamolin Foam"; Acta Dermato-Venereologica; vol. 39, pp. 428-432; 1959. cited by other.
H. Dodd, "Varicose Veins and Venous Disorders of the Lower Limb", The Irish Journal of Medicinal Science, Sixth Series, No. 400, pp. 162-174, Apr. 1959. cited by other.
A.I.S. MacPherson, "The Treatment of Varicose Veins", The Practitioner--Diseases of the Veins, vol. 183, No. 1093, pp. 11-18, Jul. 1959. cited by other.
F.R. Methiesen, "Subclinical Deep Venous Damage After Sclerosing Injection Demonstrated by Phlebography", Acta Chirugica Scandinavica, vol. 118, Fasc. 2, pp. 155-166, 1959. cited by other.
C. Oliver, "Surgical Treatment of Trophic Ulcers of the Inferior Members", Journal de Chirurgie, vol. 78, No. 2, pp. 157-174, Oct. 1959 and translation into English. cited by other.
K.R. Ramstad et al., " Operative Treatment of Varicose Veins--Follow-up of Patients Treated with ligature/injection and " Stripping"respectively", Tidsskrift for Den Norske Laegeforening, No. 10, pp. 623-625, May 1959. cited by other.
V. Gorisch et al., "Expiration of labeled oxygen after intravenous insufflation", Medicina Experimentalis, vol. 1, pp. 333-338, 1959, with Abstract in English. cited by other.
I. Berson, "Sclerotization or surgery in the treatment of varicose veins of the inferior extremities", University Clinic for dermato-venerology, Lausanne, pp. 485-190, 1960 and translation into English. cited by other.
J. Marmasse, "Sclerosing Injections in the Saphenofemoral Junction of the Saphenous Veins. Exploration, Injection, Critique", La Semaine des Hopitaux, vol. 36, No. 17, pp. 1086-1095, Apr. 1960 and translation into English. cited by other.
F.R. Mathiesen, "Treatment of Varicose Veins--Retrograde Injection or Communicant Resection", Nordisk Medicin, vol. 64, No. 48, pp. 1525-1529, 1960 and translation into English. cited by other.
P. Sicard, "Sclerosing Treatment of Varicose Veins of the Lower Limbs", Therapeutics, vol. 36, No. 2, pp. 127-129, Feb. 1960 and translation into English. cited by other.
W. Stem, "Varicose Veins", The Medical Journal of Australia, vol. II, No. 18, pp. 849-852, Oct. 29, 1960. cited by other.
F. Voss, "Special Methods in the Sclerotherapy of Venous Leg Maladies", Zeitschrift for Haut-und Geschlechts-Krankheiten, vol. XXVII, No. 9, pp. 304-306, 1960 and translation into English. cited by other.
W.G. Fegan, "Continuous Uninterrupted Compression Technique of injecting Varicose Veins", Proceedings of the Royal Society of Medicine, vol. 53, No. 7, pp. 837-840, Jul. 1960. cited by other.
V. Gorisch et al., "Appearance of intravenously given radioactive oxygen in expired air, Naunyn-Schmiedebergs Archiv fuer Experimentelle Pathologie und Pharmakologie", vol. 238, pp. 106-107, 1960, with Abstract in English. cited by other.
K. Sigg et al., "New Sclerosing Substances for Varicose Veins", Munchener Medizinische Wochenschrift, Issue 1, Mar. 1961 and translation into English. cited by other.
J.T. Hobbs, "The Treatment of Varicose Veins in Dublin", Clinical Supplement, pp. 57-60, 1961. cited by other.
A. Wiedmann, "The Varicose Symptom Complex", Report on the Literature from the years 1955-1960, Part 1, Varices, Der Hautarzt, vol. 12, No. 9, pp. 385-391, Sep. 1961 and translation into English. cited by other.
Von. A. Wiedmann, "Varicose Veins", Der Hautarzt, Year 12, No. 10, pp. 433-438, Oct. 1961 and translation into English. cited by other.
E. Gunther, "On the indication and method of sclerotherapy", Arztiche Fortbildung, vol. 55, Brochure 22, pp. 1296-1298, Nov. 1961 and translation into English. cited by other.
R. Rauhs, "Sclerotherapy, its indications and treatment successes", Klinische Medizin, Issue 1, pp. 5-12, Jan. 1961 and translation into English. cited by other.
W. Scneider, "Regarding non-operative varicosclerosation", Die Medizinische Welt, vol. 3, No. 5, pp. 225-227, Feb. 1961 and translation into English. cited by other.
K. Sigg. "Treatment of Varices, varicose ulcer and thrombosis", Vienna Medical Weekly Journal, No. 6, Feb. 11, 1961 and translation into English. cited by other.
L. Gerson, "The Treatment of Varicose Veins, A Critical Study of Choice of Method", Angiology, The Journal of Vascular Diseases, vol. 13, No. 16, pp. 260-264, 1962. cited by other.
W. Maurer, "Is the sclerosing therapy in the case of varicose advisable in practice?", Therapie der Gegenwart, Issue 5, pp. 242-245, May 1961 and translation into English. cited by other.
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|
| Abstract: |
Injectable microfoam for scleroteraphy. The sclerotherapy of varices is based on the injection of liquid substances capable of suppressing them. The present invention relates to the preparation of sclerosing substances in the form of a microfoam. The microfoam is prepared with sclerosing agents, and is then injected in the vein to be treated, so that the microfoam displaces the blood contained in the vein and provides for the contact of the sclerosing agent with the vascular endothelium, with a predetermined known concentration and during a controllable time. |
| Claim: |
What is claimed is:
.[.1. Prepared or extemporaneously prepared injectable microfoam for therapeutic uses characterized in that the microfoam is prepared with any sclerosing substance..].
.[.2. Injectable microfoam for therapeutic uses, according to claim 1, characterized in that the sclerosing substance is polydocanol..].
.[.3. Injectable microfoam for therapeutic uses, according to claim 1, characterized in that the sclerosing substance is sodium tetradecyl sulfate..].
.[.4. Injectable microfoam for therapeutic uses, according to claim 1, characterized in that the sclerosing substance is a hypertonic glucostated or glucosaline solution..].
.[.5. Injectable microfoam for therapeutic uses, according to claim 1, characterized in that the sclerosing substance used is chromated glycerol..].
.[.6. Injectable microfoam for therapeutic uses, according to claim 1, characterized in that the sclerosing substance used is ethanolamine oleate..].
.[.7. Injectable microfoam for therapeutic uses, according to claim 1, characterized in that the sclerosing substance used is sodium morrhuate..].
.[.8. Injectable microfoam for therapeutic uses, according to claim 1, characterized in that the sclerosing substance used is any iodated solution..].
.[.9. A method for phlebologic treatment comprising injecting the microfoam of claim 1 into vessels to be treated..].
.[.10. A method for phlebologic treatment comprising injecting the microfoam of claim 2 into vessels to be treated..].
.[.11. A method for phlebologic treatment comprising injecting the microfoam of claim 3 into vessels to be treated..].
.[.12. A method for treatment of esophageal varices comprising injecting the microfoam of claim 1 into vessels to be treated..].
.[.13. A method for treatment of esophageal varices comprising injecting the microfoam of claim 2 into vessels to be treated..].
.[.14. A method for treatment of esophageal varices comprising injecting the microfoam of claim 3 into vessels to be treated..].
.[.15. A method for proctologic treatment comprising injecting the microfoam of claim 1 into vessels to be treated..].
.[.16. A method for proctologic treatment comprising injecting the microfoam of claim 2 into vessels to be treated..].
.[.17. A method for proctologic treatment comprising injecting the microfoam of claim 3 into vessels to be treated..].
.[.18. A method for angiologic treatment comprising injecting the microfoam of claim 1 into vessels to be treated..].
.[.19. A method for angiologic treatment comprising injecting the microfoam of claim 2 into vessels to be treated..].
.[.20. A method for angiologic treatment comprising injecting the microfoam of claim 3 into vessels to be treated..].
.Iadd.21. An injectable microfoam for therapeutic use that is prepared or extemporaneously prepared comprising at least one sclerosing substance chosen from polidocanol, sodium tetradecyl sulfate, hypertonic glucosated solutions, hypertonicglucosaline solutions, chromated glycerol, ethanolamine oleate, sodium morrhuate, and iodated solutions, and a gas component, wherein the gas component consists essentially of oxygen or a mixture of oxygen and carbon dioxide..Iaddend.
.Iadd.22. The injectable microfoam of claim 21, wherein the at least one sclerosing substance is polidocanol..Iaddend.
.Iadd.23. The injectable microfoam of claim 21, wherein the microfoam further comprises at least one substance with a foaming capacity..Iaddend.
.Iadd.24. The injectable microfoam of claim 21, wherein the at least one sclerosing substance is sodium tetradecyl sulfate..Iaddend.
.Iadd.25. The injectable microfoam of claim 23, wherein the at least one substance with a foaming capacity is chosen from polysorbate 20, polysorbate 80, and polygeline..Iaddend.
.Iadd.26. A method of phlebologic treatment comprising injecting an effective amount of a prepared or extemporaneously prepared injectable microfoam into a vessel in need of phlebologic treatment, wherein said injectable microfoam comprises atleast one sclerosing substance chosen from polidocanol, sodium tetradecyl sulfate, hypertonic glucosated solutions, hypertonic glucosaline solutions, chromated glycerol, ethanolamine oleate, sodium morrhuate, and iodated solutions, and a gas component,wherein the gas component consists essentially of oxygen or a mixture of oxygen and carbon dioxide..Iaddend.
.Iadd.27. The method of claim 26, wherein the at least one sclerosing substance is ploidocanol..Iaddend.
.Iadd.28. The method of claim 26, wherein the microfoam further comprises at least one substance with a foaming capacity..Iaddend.
.Iadd.29. The method of calim 26, wherein the at least one sclerosing substance is sodium tetradecyl sulfate..Iaddend.
.Iadd.30. The method of claim 26, wherein the at least one substance with a foaming capacity is chosen from polysorbate 20, polysorbate 80, and polygeline..Iaddend.
.Iadd.31. A method of angiologic treatment comprising injecting an effective amount of a prepated or extemporaneously prepared injectable microfoam into a vessel in need of angiologic treatment, wherein said injectable microfoam comprises atleast one sclerosing substance chosen from polidocanol, sodium tetradecyl sulfate, hypertonic glucosated solutions, hypertonic glucosaline solutions, chromated glycerol, ethanolamine oleate, sodium morrhyatem and iodated solutions, and a gas component,wherein the gas component consists essentially of oxygen or a mixture of oxygen and carbon dioxide..Iaddend.
.Iadd.32. The method of claim 31, wherein the at least one sclerosing substance is polidocanol..Iaddend.
.Iadd.33. The method of claim 31, wherein the microfoam further comprises at least one substance with a foaming capacity..Iaddend.
.Iadd.34. The method of claim 31, wherein the at least one sclerosing substance is sodium tetradecyl sulfate..Iaddend.
.Iadd.35. The method of claim 33, wherein the at least one substance with a foaming capacity is chosen from polysorbate 20, polysorbate 80, and polygeline..Iaddend.
.Iadd.36. A method of treating esophageal varices comprising injecting an effective amount of a prepared or extemporaneously prepared injectable microfoam into a vessel in need of such treatment, wherein said injectable microfoam comprises atleast one sclerosing substance chosen from polidocanol, sodium tetradecyl sulfate, hypertonic glucosated solutions hypertonic glucosaline solutions, chromated glycerol, ethanolamine oleate, sodium morrhuate, and iodated solutions, and a gas component,wherein the gas component consists essentially of oxygen or an mixture of oxygen and carbon dioxide..Iaddend.
.Iadd.37. The method of claim 36, wherein the at least one sclerosing substance is polidocanol..Iaddend.
.Iadd.38. The method of claim 36, wherein the microfoam futher comprises at least one substance with a foaming capacity..Iaddend.
.Iadd.39. The method of claim 36, wherein the at least one sclerosing substance is sodium tetradecyl sulfate..Iaddend.
.Iadd.40. The method of claim 38, wherein the at least one substance with a foaming capacity is chosen from polysorbate 20, polysorbate 80, and polygeline..Iaddend. |
| Description: |
PRIOR ART
.[.Schlerosis.]. .Iadd.Sclerosis .Iaddend.of varices is based on injecting liquid substances in them, which causing a localized inflammatory reaction propitiates the elimination of these abnormal veins.
Upon injecting a sclerosing agent, a mixture thereof with the blood contained in the vein is produced and diluted in an unknown proportion. The results are uncertain (due to overdose or underdose) and limited to short varicose segments. As thesize of the varices to be injected decreases, the lesser this dilution is and the results that are obtained are more foreseeable. Nowadays, sclerosis is a technique chosen in cases of small and medium-sized varices. Surgery is used for those variceswith a diameter equal or larger than 7 mm.
Sclerosis and surgery complement each other at this time, but sclerotherapy continues without being able to be applied to large varicose trunci.
In these large sized varices, upon injecting a sclerosing substance, the concentration thereof in the vein, its homogenous distribution in the blood and the time that it is going to be in contact with the inside walls of the .[.treted.]. .Iadd.treated .Iaddend.vein are unknown.
In 1946 Orbach injected in small caliber varices some few cubic centimeters of air and verified displacement of the blood inside the vessel, which is occupied by the injected air. The sclerosing agent introduced afterwards is more effective thanif it has been injected into the blood.
In thick varices, upon injecting air, the described phenomenon of displacement of the blood by the injected air does not take place, but rather this forms a bubble inside the vein that makes the process ineffective in these vessels.
This same author conceived, a few years .[.late.]. .Iadd.later.Iaddend., injection of foam obtained by agitating in a container containing sodium tetradecyl sulfate, an anionic sclerosing detergent with a high foaming capacity.
The process turns out to be rather useless due to the large-sized bubbles formed and dangerous due to the collateral effects of the atmospheric nitrogen, not very soluble in blood.
Both methods had very little practical repercussion as they were used only in small varices.
DESCRIPTION OF THE INVENTION
This invention refers to the preparation of a sclerosing microfoam.
In accordance with the present invention it has been discovered that injecting in a horizontal position a microfoam of pharmacologically inert sterile physiological serum, it is verified that the microfoam causes displacement of the bloodcontained in the vessel, even in more developed varices, due to the fact that the pressure of the blood contained in them horizontally is low.
The lifting of the injected member decreases even more the venous pressure, facilitating the exclusive filling of the vein with microfoam; this remaining in the vessel while the patient is not lifted from the examination table.
Upon replacing the prepared microfoam with the physiological serum by microfoam prepared with a sclerosing agent and injecting it in the vein, this displaces the blood that the vein contains and guarantees the contact of the sclerosis agent withthe endothelium of the vein, at a known concentration and for a controllable amount of time, achieving sclerosis of the entire occupied segment.
The advantages of this process allow:
1. To know the concentration of the sclerosing agent in the vessel, as the microfoam displaces the blood and is not diluted in it like a liquid in it.
2. To guarantee the homogenous distribution of the product of sclerosis in the inside thereof.
3. To control the time in which it is kept in contact with the inside walls of the vein.
All of these factors are not known exactly nor are they controllable with the use of liquid sclerosing agents.
The elaboration of the present invention is carried out with the preparation of a microfoam with any sclerosing agent, such as: .[.polydocanol.]. .Iadd.polidocanol.Iaddend., sodium .[.tetradecly.]. .Iadd.tetradecyl .Iaddend.sulfate, hypertonicglucosated or glucosaline solutions, chromated glycerol, ethanolamine oleate, sodium morrhuate, iodated solutions.
Once the sclerosing microfoam has been prepared by any one of the existing processes, two of which will be described hereinafter, it is introduced in any sterile vessel that can be used later to be injected in the vessels to be treated, and thatpermits the stability of the same, so that it can be removed by a syringe, or by any other instrument that allows injection thereof into the vessels to be treated.
EXAMPLE 1
The preparation of the sclerosing microfoam is done by mixing in a sterile, hermetic container and connected if desired to a bottle under oxygen pressure, mixture of oxygen and carbon .Iadd.dioxide .Iaddend.or other physiological .[.gasses.]. .Iadd.gases.Iaddend.; mechanical beating is carried out by means of a micromotor that makes an ecouvillon submerged in the sclerosing solution to be foamed turn.
Beating between 8,000 and 15,000 rpm, for a time between 60 and 120 seconds, the microfoam is achieved.
This is introduced into any container that can be used for subsequent storage and later injection into the veins to be sclerosed.
In the event that the sclerosing agent does not have a foaming capacity Polysorbate 20, Polysorbate 80, Polygeline or any other substance with a foaming capacity accepted as inert for intravenous use is added to it.
EXAMPLE 2
The sclerosing agent is introduced into a hermetic, pressurized and sterile container and by stirring the solution the microfoam is achieved, with a outlet from the container for its subsequent use.
.Iadd.The invention can also embrace prepared or extemporaneously prepared injectable microfoam for therapeutic uses characterized in that the microfoam is prepared with any sclerosing substance. In one embodiment, the sclerosing substance inthe injectable microfoam is polidocanol. In another embodiment, it is sodium tetradecyl sulfate. In a further embodiment, it is a hypertonic glucostated or glucosaline solution. In still another embodiment, the sclerosing substance can be chromatedglycerol. The sclerosing substance in another embodiment is ethanolamine oleate. Another embodiment could envisage sodium morrhuate as the sclerosing substance. Still another, envisages any iodated solution.
The present invention also uses the inventive microfoam in phlebology. The sclerosing substance in the microfoam can be polidocanol or sodium tetradecyl sulfate.
The present invention also uses the inventive microfoam in the treatment of esophageal varices. The sclerosing substance in the microfoam can be polidocanol or sodium tetradecyl sulfate.
The present invention also uses the inventive microfoam in a proctology. The sclerosing substance in the microfoam can be polidocanol or sodium tetradecyl sulfate.
The present invention also uses the inventive microfoam in angiology. The sclerosing substance in the microfoam can be polidocanol or sodium tetradecyl sulfate..Iaddend.
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