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Title: Method for therapy of
liver tumors
United States Patent: 7,220,425
Issued: May 22, 2007
Inventors: Vorozhtsov;
Georgy Nikolaevich (Moscow, RU), Galperin; Eduard Izrailevich (Moscow,
RU), Goloschapov; Roman Sergeevich (Moscow, RU), Grachev; Sergei
Vitalievich (Moscow, RU), Dyuzheva; Tatyana Gennadievna (Pavshino, RU),
Kazachkina; Natalya Ivanovna (Moskovskaya oblast, RU), Kalia; Oleg
Leonidovich (Moscow, RU), Luzhkov; Yury Mikhailovich (Moscow, RU),
Lukyanets; Evgeny Antonovich (Moscow, RU), Nakhamiyaev; Vadim Romanovich
(Moscow, RU)
Assignee: Federalnoe
Gosudarstvennoe Unitarnoe Predpriyatie Gosudarstvenny Nauchny Tsentr "Nauchno-Issledovatelsky
Institut Organicheskikh Poluproduktov I Krasitelei" (FGUP GNTTS "Niopik")
(Moscow, RU), Gosudarstevennoe Obrazovatelnoe Uchrezhdenie Vysshego
Professionalnogo Obrazovaniya Moskovskaya Meditsinskaya Akademiya IM. I.M.
Sechenova RF (Gouvpo MMA IM. I.M. Sechenova MZ RF)
Appl. No.: 10/343,602
Filed: November 26, 2001
PCT Filed: November 26,
2001
PCT No.: PCT/RU01/00505
371(c)(1),(2),(4) Date:
January 31, 2003
PCT Pub. No.: WO02/45590
PCT Pub. Date: June 13,
2002
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Pharm Bus Intell
& Healthcare Studies
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Abstract
A method for regional administration of
preparations during the therapy of liver tumor, comprising administering a
preparation into a branch of the portal vein with the simultaneous
occlusion of afferent and efferent lobe vessels (branches of the portal
vein proximal the place of puncture, branches of the hepatic artery and
lobar hepatic vein) for 5 15 minutes.During catalytic therapy, it is
preferable to use Teraphtalum as the preparation and to administer
ascorbic acid after termination of occlusion.During photodynamic therapy,
it is preferable to use photosens as the preparation and to carry out
irradiation of the tumor after 10 35 minutes.This method of administration
provides for the predominant accumulation of the preparations in the
target lobe (tumor carrier lobe) of the liver, their low penetration into
the systemic blood flow, which makes it possible to reduce the dose of the
preparation and its general toxicity.
Description of the Invention
FIELD OF THE
INVENTION
The present invention relates to a method
for the administration of different preparations into a liver with a tumor
lesion and may be utilized in antitumor therapy.
BACKGROUND OF THE
INVENTION
A method is known for administration of
preparations, on the example of photodynamic therapy of liver tumors, into
the hepatic artery (R. van Hillegersberg, J. P. A. Marijnissen, W. J. Kort,
P. E. Zondervan, O. T. Terpstra//Interstitial photodynamic therapy in a
rat liver metastasis model. Br. J. Cancer, 1992, 66, pp. 1005 1014).
Photophrin was used as the preparation and irradiation was carried out 48
hours after its administration.
A drawback of the method is the spread of the preparations into the
systemic blood flow, their rapid reduction in the region of damage and as
a result--an increase of the general toxicity.
SUMMARY OF THE
INVENTION
The object of the invention is to develop
a method for administration of preparations to a target lobe (tumor
carrier lobe) of the liver, ensuring their predominant accumulation in the
target lobe of the liver in combination with a small spread into the
systemic blood flow. This makes it possible to reduce the total amount of
the introduced preparation and its toxicity.
This object is achieved by introducing a chemical preparation into a
branch of the portal vein with the simultaneous occlusion of the afferent
(branches of the portal vein proximal the place of puncture and branches
of the hepatic artery) and efferent (lobar hepatic vein) vessels of the
target lobe of the liver for 5 15 minutes. Thus, direct lengthy contact
between the preparation and the target lobe of the liver, which has been
eliminated from blood circulation, is accomplished. The indicated method
makes it possible during catalytic therapy to introduce a second component
of the binary pair--ascorbic acid (AA), immediately after removal of the
occlusion with a large content of Teraphtalum (TP) in the target lobe of
the liver, and during photodynamic therapy to accomplish irradiation of
the tumor in early periods after the administration of a photosensitizer.
DISCLOSURE OF THE
INVENTION
Practically speaking, the method is
carried out in the following manner. A median laparotomy is conducted,
afferent (a branch of the portal vein and hepatic artery) and efferent (a
branch of the hepatic vein) vessels of the target lobe of the liver are
isolated. They are taken on tourniquets. A puncture of the branch of the
portal vein is made, the preparation is introduced therein, simultaneously
stopping the flow of blood: the blood inflow--through branches of the
portal vein (proximal to the place of puncture) and the hepatic artery,
outflow--through a branch of the hepatic vein. Restoration of the blood
flow is accomplished by removing clamps from the vessels 5 15 minutes
after administration of the preparation.
The following data illustrate the method according to the invention.
Teraphtalum (cobalt octacarboxy phthalocyanine) (TP) and Photosens (a
mixture of diulfonated, trisulfonated, and tetrasulfonated derivatives of
aluminum phthalocyanine) (PS) (GNTs RF "NIOPIK," Moscow) were used as the
preparations.
Claim 1 of 2 Claims
1. A method of catalytic therapy of a
liver tumor comprising: occluding afferent and efferent vessels of a
target lobe of the liver for 5 15 minutes; and administering a cobalt
octacarboxy phthalocyanine preparation into a portal vein of the target
lobe of the liver (tumor carrier lobe) during occlusion. ____________________________________________
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