Injectable microfoam containing a sclerosing agent

- BTG International Ltd.

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.

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Description

This is a continuation of international application Serial No. PCT/ES94/00064, filed Jun. 21, 1994.

Notice: More than one reissue application has been filed for the reissue of U.S. Pat. No. 5,676,962, which is a continuation of international application Serial No. PCT/ES94/00064, filed Jun. 21, 1994. The reissue applications are application No. 10/941,013 (the present application), filed Sep. 15, 2004, which is a continuation application of 10/458,806, filed Jun. 11, 2003, now Reissue Pat. No. 38,919.

PRIOR ART

Schlerosis Sclerosis 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 the size 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 varices with 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 treated 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 than if 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 later, 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 blood contained 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 with the 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 polidocanol, sodium tetradecly tetradecyl sulfate, hypertonic glucosated 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 that permits 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 dioxide or other physiological gasses gases; mechanical beating is carried out by means of a micromotor that makes an écouvillon 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.

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 in the 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 chromated glycerol. 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.

Claims

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.

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, 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.

22. The injectable microfoam of claim 21, wherein the at least one sclerosing substance is polidocanol.

23. The injectable microfoam of claim 21, wherein the microfoam further comprises at least one substance with a foaming capacity.

24. The injectable microfoam of claim 21, wherein the at least one sclerosing substance is sodium tetradecyl sulfate.

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.

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 at least 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.

27. The method of claim 26, wherein the at least one sclerosing substance is ploidocanol.

28. The method of claim 26, wherein the microfoam further comprises at least one substance with a foaming capacity.

29. The method of calim 26, wherein the at least one sclerosing substance is sodium tetradecyl sulfate.

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.

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 at least 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.

32. The method of claim 31, wherein the at least one sclerosing substance is polidocanol.

33. The method of claim 31, wherein the microfoam further comprises at least one substance with a foaming capacity.

34. The method of claim 31, wherein the at least one sclerosing substance is sodium tetradecyl sulfate.

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.

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 at least 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.

37. The method of claim 36, wherein the at least one sclerosing substance is polidocanol.

38. The method of claim 36, wherein the microfoam futher comprises at least one substance with a foaming capacity.

39. The method of claim 36, wherein the at least one sclerosing substance is sodium tetradecyl sulfate.

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.

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  • F. Jaeger, “Primary or Secondary Varicose Veins”, Die Medizinische, No. 36, pp. 1237-1340, Sep. 1955 and translation into English.
  • 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.
  • F. Schürcher, “For the Practice Varicose Veins and Deep Chronic Crural Thrombosis”, Münchener Medizinische Wochenschrift, No. 41, pp. 1354-1358, Oct. 14, 1955 and translation into English.
  • K. Sigg. “The Treatment of Leg Ulcers”, Die Medizinische, No. 17, pp. 646-648, 1955 and translation into English.
  • K. Sigg, “Therapeutic Issues—On the Treatment of Vein Thrombosis with Butazolidin”, Schwetzerische Medizinische Wochenschrift, 65th year of the edition, No. 11, pp. 261-262, Mar. 12, 1955 and translation into English.
  • 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.
  • Flückinger, 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.
  • R.W. Décoppet, “The Sclerotherapy of Varices with Thrombophilic Patients”, Swiss Medical Weekly Journal, 86th year, No. 20, pp. 509-513, May 19, 1956 and translation into English.
  • R. May, “Impairments and Risks of the Treatment of Varicose Veins”, Münchener Medizinische Wochenschrift, No. 1, pp. 13-16, Jan. 1956 and translation into English.
  • 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.
  • K. Sigg, “Varicose Veins and Deep Seated Chronic Leg Vein Thrombosis” Münchener Medizinische Wochenschrift, vol. 98, No. 8, pp. 260-263, Feb. 1956.
  • 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.
  • 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.
  • 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 into English.
  • 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.
  • 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.
  • R.R. Foote, “Varicose Vein Problems in General Practice”, The Practitioner—Medical Etiquette, vol. 179, No. 179, pp. 59-66, Jul. 1957.
  • 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.
  • 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.
  • 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.
  • Von H. Westhues et al., “The Varicose Symptom Complex”, Medizinsche Klinik, No. 16, pp. 657-660, 1957, and translation into English.
  • 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 into English.
  • K. Sigg, “New Approaches to the Treatment of Thrombosis”, Angiology—The Journal of Vascular Diseases, vol. 8, No. 1, pp. 44-59, Feb. 1957.
  • K. Sigg et al., “Prophylaxis of Thrombosis during Gravidity”, Die Medizinische, No. 12, pp. 420-423, Jan. 1957 and translation into English.
  • F. Jaeger, “Varcose Veins”, Deutsche Medizinische Wochenschrift, vol. 83, No. 30, p. 1295, Jul. 1958, and translation into English.
  • K. Sigg, “Prevention and Treatment of Thromboembolic Complications”, Wiener Medizinische Wochenschrift, No. 10, pp. 206-213, Mar. 1958, and translation into English.
  • 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.
  • 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.
  • A Lemaire et al., “Effect of Intra-arterial oxygen injection on blood cholesterol”, Therapie, vol. 13, pp. 395-399, 1958, with Abstract in English.
  • A. Ree; “The Treatment of Varicose Veins with Etamolin Foam”; Acta Dermato-Venereologica; vol. 39, pp. 428-432; 1959.
  • 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.
  • A.I.S. MacPherson, “The Treatment of Varicose Veins”, The Practitioner—Diseases of the Veins, vol. 183, No. 1093, pp. 11-18, Jul. 1959.
  • F.R. Methiesen, “Subclinical Deep Venous Damage After Sclerosing Injection Demonstrated by Phlebography”, Acta Chirugica Scandinavica, vol. 118, Fasc. 2, pp. 155-166, 1959.
  • 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.
  • 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.
  • V. Gorisch et al., “Expiration of labeled oxygen after intravenous insufflation”, Medicina Experimentalis, vol. 1, pp. 333-338, 1959, with Abstract in English.
  • 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.
  • 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.
  • 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.
  • 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.
  • W. Stem, “Varicose Veins”, The Medical Journal of Australia, vol. II, No. 18, pp. 849-852, Oct. 29, 1960.
  • F. Voss, “Special Methods in the Sclerotherapy of Venous Leg Maladies”, Zeitschrift för Haut-und Geschlechts-Krankheiten, vol. XXVII, No. 9, pp. 304-306, 1960 and translation into English.
  • 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.
  • 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.
  • K. Sigg et al., “New Sclerosing Substances for Varicose Veins”, Munchener Medizinische Wochenschrift, Issue 1, Mar. 1961 and translation into English.
  • J.T. Hobbs, “The Treatment of Varicose Veins in Dublin”, Clinical Supplement, pp. 57-60, 1961.
  • 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.
  • Von. A. Wiedmann, “Varicose Veins”, Der Hautarzt, Year 12, No. 10, pp. 433-438, Oct. 1961 and translation into English.
  • E. Günther, “On the indication and method of sclerotherapy”, Ärztiche Fortbildung, vol. 55, Brochure 22, pp. 1296-1298, Nov. 1961 and translation into English.
  • R. Rauhs, “Sclerotherapy, its indications and treatment successes”, Klinische Medizin, Issue 1, pp. 5-12, Jan. 1961 and translation into English.
  • W. Scneider, “Regarding non-operative varicosclerosation”, Die Medizinische Welt, vol. 3, No. 5, pp. 225-227, Feb. 1961 and translation into English.
  • K. Sigg. “Treatment of Varices, varicose ulcer and thrombosis”, Vienna Medical Weekly Journal, No. 6, Feb. 11, 1961 and translation into English.
  • 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.
  • 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.
  • J.P. Medelman, “History of the Section on Radiology”, The Journal of the American Medical Association, vol. 178, No. 8, pp. 785-911, Nov. 25, 1961.
  • H. Dodd, “Varicose Veins and Venous Disorders of the Lower Limb”, The Proceedings of the Cardiff Medical Society, pp. 28-45, 1962.
  • H.O. Schneider, “Varix Treatment with Modern Sclerosing Agent”, Zeitschrift för Haut und Geschelchtskrankheiten, Band XXXIII, Heft No. 5, pp. 163-166, Sep. 1962 and translation into English.
  • I. Singh, “Life Without Breathing”, Arch. int. Pharmacodyn., vol. CXXXVIII, No. 3-4, pp. 318-330, 1962.
  • P. Flöckiger et al., “Physical and Biological Pathogenetic Components of Varicosis”, Schweizer Medizinische Wochenschrift, No. 45, 1963.
  • E.J. Orbach, “Misconceptions and Pitfalls in Sclerosing Therapy of Varicose Veins”, Angiology—The Journal of Vascular Diseases, vol. 14, No. 11, pp. 552-555, Nov. 1963.
  • O. Gilje, “Injection Treatment of Varicose Veins”, Den norske Legeforening No. 17, pp. 1380-1381, Sep. 1963 and translation into English.
  • J.C. Luke et al., “Factors in the Improvement of Results in Varicose Vein Surgery”, Improved Vein Surgery, Canadian Journal of Surgery, vol. 6, No. 2, pp. 145-148, Apr. 1963.
  • K. Sigg, “Varicosis and Thrombosis during Pregnancy, birth and in childbed”, Zentralblatt för Gynäkologie, No. 8, pp. 254-259, Feb. 23, 1963 and translation into English.
  • E.C. Emerson, “A Reappaisal of the Injection Treatment of Varicose Veins”, Angiology The Journal of Vascular Diseases, vol. 14, No. 1, pp. 8-13, Jan. 1963.
  • P. Flöckiger et al., “A Contribution to the Techniques for Outpatient Treatment of Varicose Veins”, Lecture delivered at the meeting of the German Working Group on Phlebology and the Hamburg Dermatological society on Oct. 20, 1962, Med. Welt 1963, No. 12, pp. 617-621.
  • W.G. Fegan et al., “A Modern approach to the injection treatment of varicose veins and its applications in pregnant patients”, American Heart Journal, vol. 68, No. 4, pp. 757-764, Oct. 1964.
  • H.J. Leu et al., “The Modern Conception of Therapy of Varicose Veins”, Angiology, The Journal of Vascular Diseases, vol. 15, No. 9, pp. 371-378, Sep. 1964.
  • E.J. Orbach, “A Unified Approach to the Therapy of Varicosities”, Angiology, vol. 15, No. 12, pp. 558-560, Dec. 1964.
  • R. Santler, “Sclerosing Therapy of Varicose Veins”, Weiner Klinische Wochenschrift, Issue 24, No. 76, pp. 431-434, Jun. 12, 1964 and translation into English.
  • W.Schneider et al., “On the histology of the Varicose Injection Treatment in People with new Injection Treatment Agents”, Archive for Clinical and Experimental Dermatology, vol. 220, pp. 234-249, 1964 and translation into English.
  • K. Sigg, “Treatment of Varicose Veins in 2-5 days”, Dermatologica, vol. 129, No. 2, pp. 111-117, 1964 and translation into English.
  • K. Sigg, “La Profilassi e la terapia delle malattie venose degli arti inferiori mediante la compressione con fasciature e con calze elastiche”, Minerva Ginecologica, vol. 16, No. 19, pp. 817-823, Oct. 15, 1964.
  • E.J. Orbach, “Article on Treatment of Teleangiectasias”, Zentralblatt för Phlebologie, Heft 1, Band 3, pp. 4-7, Feb. 15, 1964 and translation into English.
  • Von H. Pfosi, “On the Sclerosing Treatment of Varicose Veins”, Schweizensche Rundschau för Medizin—Revue Suisse de Medecine, 54th year of Edition, No. 29, pp. 868-871, Jul. 22, 1965 and translation into English.
  • K. Sigg, “Varicose Vein Therapy”, Deutsche MEdizinische Wochenschrift, No. 15, pp. 665-666, Apr. 9, 1965 and translation into English.
  • R. Tournay, Indication of the Exclusive Sclerotherapy or the Consecutive Combination Therapy Surgery-Sclerotization of Varicose Veins, Zentralblatt for Phlebologie, vol. 4, No. 1, pp. 133-142, Feb. 15, 1965 and translation into English.
  • E.J. Orbach, “The Place of Injection Therapy in the Treatment of Venous Disorders of the Lower Extremity—with Comment on its Technique”, Presented at the Annual Meeting of the International College of Angiology, London, pp. 18-23, Jul. 1965.
  • C. Olivier et al., “Reinterventions Performed on Primary Varicose Veins of the Lower Limbs”, La Presse Medicafe, vol. 74, No. 26, pp. 1355-1360, May 25, 1966 and translation into English.
  • E.J. Orbach, “The Place of Injection Therapy In the Treatment of Venous Disorders of the Lower Extremity—with Comments on its Techinque”, Angiology—The Journal of Vascular Diseases, vol. 17, No. 1, pp. 18-23, Jan. 1966.
  • G. Fegan, “The Treatment of Venous Insufficiency During Pregnancy”, Varicose Veins—Compression Sclerotherapy, Chapter VII, pp. 93-98, 1967.
  • M.D.H.-D. Bock; “Varicosis and its Therapy”; Arztliche Praxis; XIX Volume, No. 60, pp. 2146-2148; Jul. 29, 1967 and translation into English.
  • P.Flöckiger, “Intraoperative Varicosclerosation with Sodium Tetradecyl Foam in the Babcock Operation”, Zentralblatt for Phlebologie, Heft 1, Band 6, pp. 514-518, Feb. 1967 and translation into English.
  • K. Sigg, “Sclerotherapy in the Treatment of Varicose Veins”, Internist, pp. 388-398, 1967 and translation into English.
  • Dr. E. Lunkenheimer; letter to Chem. Fabrik Kreussler & Co.; Mar. 20, 1967 and translation into English.
  • B. Ya Varshavskii, “Mechanism of Changes in Renal Activity Following intravenous oxygen”, vol. 53, No. 2, pp. 173-177, 1967, with Abstract in English.
  • O. Henschel;“Die Varizenverördening—Verördungstherapie mit Aethoxysklerol—Kreussler”; p. 22; 1968 and translation into English.
  • W.K. Blenkinsopp, “Effect of Injected Sclerosant (Tetradecyl Sulphate of Sodium) on Rat Veins”, Angiologica, vol. 5, No. 6, pp. 386-396, 1968.
  • E. Frugis et al., “Telangieceasia Sclerotherapy of the Lower Limbs”, Minerva Dermatologica, vo. 43, pp. 368-371; 1968 and translation into English.
  • J. Orbach, “Varicose Veins”, Medical Trial Technique Quarterly, vol. XIV, No. 4, pp. 27-38, Jun. 1968.
  • J. Steinacher et al., “Path and Retention Time of a Contrast Medium in the Superficial Venous System under the Conditions of the Varix Obliteration. A Study on the method of varix obliteration”, Zsch. Haut-Geschi, vol. 43, No. 9, pp. 369-376, 1968 and a translation into English.
  • J.T. Hobbs, “The Treatment of Varicose Veins—A Random Trial of Injection-Compression Therapy Versus Surgery”, Brit. J. Surg. vol. 55, No. 10, pp. 777-780, Oct. 1968.
  • H. Elechenberger, “Result of the Sclerotherapy of Varicose Veins with Hydroxpolyaethoxy-Dodecan”, Zentralblatt för Phlebologie, vol. 8, pp. 181-183, 1969 and translation into English.
  • K. Sigg, “Phlebosclerosation: experience and results”, Der Chirurg, vol. II, No. 40, pp. 487-491, 1969 and translation into English.
  • 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.
  • B. Stemmer et al., Phlebologie, vol. 22, pp. 151-172, Apr.-Jun. 1969 and translation into English.
  • G. Wesener, “Morphology and new therapies for starburst varicosis and essential telangiectasia”, Berufs-Dermatosen, vol. 17, No. 5, pp. 273-281, Oct. 1969 and translation into English.
  • W.K. Blenkinsopp, “Choice of Sclerosant: An Experimental Study”, Angiologica, vol. 7, No. 3, pp. 182-186, 1970.
  • K. Holzegel, “On Sclerosing Agents for Varicose Veins”, Zentralblatt för Phlebologie, vol. 9, pp. 43-53, 1970 and translation into English.
  • B. Stemmer, “Comparison of Common Sclerosing Techniques”, Zentralblatt for Phlebologie, vol. 3, pp. 170-176, 1970 and translation into English.
  • J. Edmonds-Seal et al., “Air Embolism”, Anaesthesia, vol. 26, No. 2, pp. 202-208, Apr. 1971.
  • H.J. Leu et al., “The Combined Surgical-Sclerotic Ambulatory Treatment of Saphenous Varicose Veins”, Schweizerische Rundschau för Medizin, vol. 1, No. 61, pp. 1360-1364, Oct. 31, 1972 and translation into English.
  • K. Sigg, “Technical Details about Injecting Varices”, Med. Klin., vol. 67, No. 27/28, pp. 955-959, 1972 and translation into English.
  • Z. Salamon, “Sclerosing Agents—Toxicity and Mechanism of Action”, Wiadomosci Lekarskie, vol. 26 (19), pp. 1819-1822, 1973 and translation into English.
  • W.G. Fegan, “Conservative Treatment of Varicose Veins”, Progr. Surg. vol. 11, pp. 37-45, 1973.
  • P. Flöckiger, “Der Erythem-Test im Rahmen der präoerativen Varizenuntersuchung”, Praktische Hinweise-Practical Advice, vol. 3, No. 2, pp. 198-199, 1974.
  • S. Efunin et al., “Oxygen Parameters of Blood and Tissues during Intravascular Oxygenation of the Organism”, Eksperimental'naya Khirurgiya I Anesteziologiya, vol. 5, pp. 183-186, 1974, with Abstract in English.
  • E.J. Orbach, “The importance of removal if postinjection coagula during the course of sclerotherapy of vaircose veins”, VASA, vol. 3, No. 4, pp. 475-477, 1974.
  • J.T. Hobbs, “Surgery and Sclerotherapy in the Treatment of Varicose Veins”, Arch. Surg. vol. 109, pp. 793-796, Dec. 1974.
  • E.J. Orbach et al., “Investigation of the Different Injection Techniques in the Sclerotherapy of Varicose Veins by Minidose and Differential Pressure Phlebography”, VASA, vol. 4, No. 2, pp. 175-183, 1975.
  • K. Sigg, “Quick Treatment—a modified Method of Sclerotherapy of Varicose Veins”, Zur Diskussion gestellt—Open for Discussion, VASA, vol. 4, No. 1, pp. 73-78, 1975.
  • H.L. Myers, “Injection Therapy for Varicose Veins”, The Journal of Family Practice, vol. 3, No. 5, pp. 531-534, 1976.
  • E.J. Orbach, “Controversies and Realities of Therapy of Varicosis”, International Surgery, vol. 62, No. 3, pp. 149-151, Mar. 1977.
  • J. Hobb, “Surgery or Sclerotherapy for Varicose Veins”, Archs. Surg. Nol. 109, p. 793, 1974.
  • P. Ouvry et al., “Aetoxisclerol: First Impression”, vol. 31, No. 2, pp. 75-77, 1978 and translation into English.
  • D. Reinharez, “Perforating Vein Sclerosis Technique”, Ph Phlëbologie, vol. 31, No. 2, pp. 69-74, 1978 and translation into English.
  • K. Sigg et al., “Treating varices with Sclerotherapy”, Langenbacks Arch. Chir., vol. 347, pp. 231-234, 1978 and translation into English.
  • E.J. Orbach, “Hazards of Sclerotherapy of Varicose Veins—their prevention and treatment of complications”, VASA, vol. 8, No. 2, pp. 170-173, 1979.
  • P. Ouvry., “Sclerosant Treatment of Tetangiectasias of the Lower Limbs”, Phlëbologie, vol. 32, No. 4, pp. 365-370, 1979 and translation into English.
  • W. DeGroot, “Techniques of Sclerotherapy for Sunburst Venous Blemishes”, J. Dermatol. Surg. Oncol. vol. 11, No. 7, pp. 696-704, Jul. 1985.
  • D.S. Camara et al., “The Hemodynamic Effects of the Sclerosant Sodium Morrhuate in Dogs”, Surgery—Gynecology and Obstetrics, vol. 161, No. 4, pp. 327-331, Oct. 1985.
  • A. Davy et al., “Ostial Incompetence—Sclerosis or Resection?”, Phlëbologie, vol. 39, No. 1, pp. 35-45, 1986 and translation into English.
  • F.B. Cockett, “Arterial Complications during Surgery and Sclerotherapy of Varicose Veins”, Phlebology, vol. 1, pp. 3-6, 1986.
  • M.P. Goldman et al., “Continuing Medical Education (Dermatologic Surgery), Treatment of Telangiectasia: A review”, Journal of the American Academt of Dermatology, vol. 17, No. 2, part 1, pp. 167-182, Aug. 1987.
  • E. Morsiani et al., “Effect of Intravenous and Intreperivenous Injections of Sclerosants (Sodium Tetradecyl Sulfate and Hydroxy Polyethoxy Dodecan) on the Rat Femoral Vein”, Research in Experimental Medicine, vol. 187, pp. 439-449, 1987.
  • P. Ouvry et al., “Sclerotherapy of Perforating Veins”, Phlëbologie, vol. 40, No. 3, pp. 633-641, 1987 and translation into English.
  • L. Karmazsin et al., “Experimental Study of Lipid Peroxidation Following Intravenous Oxygen”, Kiserletes Orvostudomany, vol. 39, pp. 342-348, 1987, with Abstract in English.
  • J.T. Hobbs, “Compression Sclerotherapy in Venous Insufficiency”, Acta Chir Scand Suppl., vol. 544, pp. 75-80, 1988.
  • 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.
  • E.L. Bodian et al., “Treatment of Varicose Veins; Modern Concepts and Methods”, The Journal of Dermatologic Surgery and Oncology, vol. 15, No. 2, pp. 191-198, Feb. 1989.
  • M.A. Farina et al., “Outpatient Treatment of Varicose Vein Segments: Two Techniques Compared”, Phlëbologie, pp. 1070-1071, 1989 and translation into English.
  • D. Gasparini, “Therapeutic Embolization in Pulmonary Hemorrhage”, Radiologica Interventistica, vol. 77, pp. 223-229, 1989 and translation into English.
  • G. Hauer, “Diagnostic and Surgical Treatment of Varicose Veins”, Herz vol. 14, No. 5, pp. 274-282, 1989 and translation into English.
  • K.M. Hördegen, “Conconitant Circulatory Problems in the Arteries or immobility in mostly older patients make outpatient treatment of ulcers more differcult”, Schweiz. Med. Wschr., vol. 119, No. 37, pp. 1264-1269, 1989 and translation into English.
  • P.A. Ouvry, “Telangiectasia and Sclerotherapy”, J. Dermatol. Surg. Oncoo. vol. 15, No. 2, pp. 177-181, Feb. 1989.
  • R.M. Knight et al., “Ultrasonic Guidance of Injections into the Superficial Venous System”, Phlebology, pp. 339-341, 1989.
  • S.N. Vasdekis et al., “Evaluation of non-invasive and invasive methods in the assessment of short saphenous vien termination”, Br. J. Surg., vol. 76, pp. 929-932, 1989.
  • M. Masaki et al., “The destructive effects of sclerosant ethanolamine oleate on mammalian vessel endothelium”, Gastroenterologia Japanica, vol. 25, No. 2, pp. 230-235, Feb. 1990.
  • Z.B. Shafi et al., “Factors Affecting High Shear Preparation of Albumin Microspheres”, Pharmaceutical Sciences Research GRoup, p. 144P, 1990.
  • N. Weindorf et al., “Control of Sclerosis—Treatment for Varicose Veins”, Phlébologie, vol. 43, No. 4, pp. 681-689, 1990 and translation into English.
  • M.P. Goldman, M.D. “Variations on Injection Technique”, Sclerotherapy: Treatment of Varicose and Telangiectatic Leg Veins, pp. 274-275, 290, 313-323, 1991.
  • G. Belcaro et al., “Treatment of Superficial Venous Incompetence with the Savas Technique”, Journal des Maladies Vasculaires (Paris), vol. 16, pp. 23-27, 1991.
  • H.R. Bernbach, “Sclerosing Injections Using the Sigg Method”, Phlébologie, vol. 44, No. 1, pp. 31-36, 1991 and translation into English.
  • Y.A. Ershov et al., “Variant of an Operation on Enlarged Veins of the Oesophagus and Cardia in Patients with Portal Hypertension Syndrome”, Surgery—Monthly Science Practice Journal, Ministry of Health of the Union of Soviet Socialist Republics All-Union Scientific Society of Surgeons, pp. 46-49, Sep. 9, 1991 and translation into English.
  • M.P. Goldman, “Sclerotherapy Treatment of Varicose and Telangiectatic Leg Veins”, Clinical Methods for Sclerotherapy of Varicose Veins, pp. 274-275, 290, 312 and 323, 1991.
  • J.T. Hobbs, “Varicose Veins”, ABC of Vascular Diseases, vol. 303, pp. 707-710, Sep. 21, 1991.
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Patent History
Patent number: RE40640
Type: Grant
Filed: Sep 15, 2004
Date of Patent: Feb 17, 2009
Assignee: BTG International Ltd. (London)
Inventors: Juan Cabrera Garrido (Granada), Juan Cabrera Garcia-Olmedo (Granada)
Primary Examiner: Isis Ghali
Attorney: Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P.
Application Number: 10/941,013