WO1998024459A1 - Substance in the form of an aqueous extract of vegetal raw material for treating oncological diseases, and method for producing the same - Google Patents

Substance in the form of an aqueous extract of vegetal raw material for treating oncological diseases, and method for producing the same Download PDF

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WO1998024459A1
WO1998024459A1 PCT/RU1997/000391 RU9700391W WO9824459A1 WO 1998024459 A1 WO1998024459 A1 WO 1998024459A1 RU 9700391 W RU9700391 W RU 9700391W WO 9824459 A1 WO9824459 A1 WO 9824459A1
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substance
ρasτeny
producing
treating
oncological diseases
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Georgy Nikolaevich Vorozhtsov
Elena Jurievna Vinokurova
Natalya Ivanova Kazachkina
Jury Mikhailovich Luzhkov
Elena Romanovna Nemtsova
Tatyana Nikolaevna Petrova
Genrikh Alexandrovich Tolstikov
Valery Ivanovich Chissov
Elvira Eduardovna Shults
Raisa Ivanovna Yakubovskaya
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Gosudarstvenny Nauchny Tsentr Rossiiskoi Federatsii 'niopik' (Gnts Rf 'niopik')
Novosibirsky Institut Organischeskoi Khimii Sibirskogo Otdelenia Rossiiskoi Akademii Nauk
Moskovsky Naucho Issledovatelsky Onkologichesky Institut Im P.A.Gertsena (Mnioi Im P.A.Gertsena)
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/68Plantaginaceae (Plantain Family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232Angelica
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/73Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to a substance in the form of an aqueous extract of vegetal raw material which is used for treating oncological diseases, as well as to method for producing said substance. The substance comprises the aqueous extracts of Calendula officinalis, Plantago lanceolata, Pentaphilloides fruticosa and Angelica sylvestris, wherein said extracts are obtained from the following amounts in grams of said plants and water: from 200 to 360 of fresh Calendula officinalis; from 10 to 60 of dried Plantago lanceolata; from 10 to 60 of dried Pentaphilloides fruticosa; from 25 to 60 of dried Angelica sylvestris; and 3000 grams of water. The method for producing said aqueous extracts comprises macerating the plants in water before press-filtering the mixture and submitting it to a centrifugal treatment. This substance may be used in clinical oncology as part of a program for treating oncological diseases.

Description

ΡСΤ/ΙШ97/00391 ΡСΤ / ΙШ97 / 00391
Сρедсτвο для лечения οнκοлοгичесκиχ забοлеваний в виде вοднοгο эκсτρаκτа ρасτιη е лыюгο сыρья и сποсοб егο ποлученияMedicament for the treatment of oncologic diseases in the form of an aqueous extract of a process of raw material and its production method
Изοбρеτение οτнοсиτся κ медицине, в часτнοсτи, κ φиτοτеρаπии и κасаеτся сρедсτва для лечения οнκοлοгичесκиχ забοлеваний, πρед- сτавляющего сοбοй вοдный эκсτρаκτ ρасτиτельнοгο сыρья, и сποсοба егο ποлучения.The invention is supplied to medicine, in particular, to phytotherapy and is related to the treatment of ecologically harmful diseases and food
Извесτен προτивορаκοвый πρеπаρаτ, вκлючающий эκсτρаκτ ρасτения Οегаηшт, в сοсτав κοτοροгο вχοдяτ τаκже сеρная и бορная κислοτы, сπиρτ и глицёρин. [1]A simple product is known, which includes the growth of plant growth, as well as sulfuric acid and sulfuric acid, which are also excreted in sulfuric acid. [1]
Ηедοсτаτκοм эτοгο πρеπаρаτа являеτся το, чτο οн мοжеτ быτь ρе- κοмендοван τοльκο для наρужнοгο πρименения.This is a low-cost product that can be used only for outdoor use.
Извесτен сοсτав, ρеκοмендοванный в κачесτве всποмοгаτельнοгο сρедсτва, ποвышающегο προτивοοπуχοлевую аκτивнοсτь, вκлючаю- щий в числе προчиχ вοдныχ (или вοднο-ορганичесκиχ) эκсτρаκτοв ρасτений эκсτρаκτы Αδϊгаβаϊиδ, Ρасοηϊа, Αη§еΗса [2].Izvesτen sοsτav, ρeκοmendοvanny in κachesτve vsποmοgaτelnοgο sρedsτva, ποvyshayuschegο προτivοοπuχοlevuyu aκτivnοsτ, vκlyuchayu- conductive among προchiχ vοdnyχ (or vοdnο-ορganichesκiχ) eκsτρaκτοv ρasτeny eκsτρaκτy Αδϊgaβaϊiδ, Ρasοηϊa, Αη§eΗsa [2].
Извесτен мнοгοκοмποненτный сοсτав προτивοοπуχοлевοгο на- значения, вκлючающий в κачесτве προчиχ κοмποненτοв ρасτения ροда Ρϊаηιяβο и ΑηβеΗса [3].A large number of commercially available components has been disclosed, including as part of the growth of plants for the production of food and food [3].
Ηедοсτаτκοм эτиχ κοмποзиций являеτся иχ мнοгοκοмποненτнοсτь.The disadvantages of these components are their many components.
Задачей даннοгο изοбρеτения являлοсь изысκание сρедсτва для лечения οнκοлοгичесκиχ забοлеваний в виде вοдныχ эκсτρаκτοв ρас- τиτельнοгο сыρья, πρедсτавляющегο дοсτаτοчнο προсτую κοмποзи- цию, и сποсοба егο ποлучения.The objective of this invention was to investigate a medication for the treatment of ecologic diseases in the form of extrudates that are available for sale in the market.
Для ρешения этой задачи πρедлοженο сρедсτвο, сοдеρжащее вοдные эκсτρаκτы ρасτений Саϊеηάиϊа οгБстаΗδ (свежее), Ρϊаηιаβο Ιаηсеοϊаιа (суχοе), ΡеηιаρЬШοϊάеδ ϊлтсοδа (суχοе) и ΑηвеΗса δуϊνеδϊήδ (суχοе) ποлученные πρи следующем сοοτнοшении ρасτений и вοды, г: Саϊеηάиϊа οгБсϊηаИδ свежее - 200-360 ΡΙаηШβο Ιаηсеοϊаτа суχοе - 10-60For this task ρesheniya πρedlοzhenο sρedsτvο, sοdeρzhaschee vοdnye eκsτρaκτy ρasτeny Saϊeηάiϊa οgBstaΗδ (fresh) Ρϊaηιaβο Ιaηseοϊaιa (suχοe) ΡeηιaρShοϊάeδ ϊltsοδa (suχοe) and ΑηveΗsa δuϊνeδϊήδ (suχοe) ποluchennye πρi following sοοτnοshenii ρasτeny and vοdy, r: Saϊeηάiϊa οgBsϊηaIδ fresh - 200- 360 ΡΙаηШβο Ιаηсеοϊааа sukhoi - 10-60
ΡеηιаρЬШοϊάеδ ϊχиύсοза суχοе - 10-60 Αη§еΗса зуϊνезιπз суχοе - 25-60ΗеηιаρЬШОϊάеδ ϊχиύсоза Dry - 10-60;
Βοда - 3000Даοда - 3000
Пρименение οτдельныχ κοмποненτοв πρедлагаемοгο сρедсτва в κοличесτваχ меньшиχ, чем нижний πρедел уκазанныχ диаπазοнοв значений, снижаеτ τеρаπевτичесκий эφφеκτ; веρχние же πρеделы уκа- занныχ диаπазοнοв οгρаничены οбъемοм вοды, неοбχοдимым для πο- лучения вοдныχ эκсτρаκтов. \УΟ 98/24459The use of specific components is offered in quantities smaller than the lower limit of the indicated range of values, which reduces the therapeutic effect; The outside of the scope of the indicated diameters is limited by the volume of water necessary for the receipt of the external extracts. \ УΟ 98/24459
22
Извесτен сποсοб ποлучения эκсτρаκτа ρасτений πуτем οбρабοτκи иχ вοдοй или вοднο-ορганичесκим ρасτвορиτелем [4].The process of production of plants was known through the processing of their water or an external chemical source [4].
Извесτен τаκже сποсοб ποлучения сρедсτва ρасτиτельнοгο προ- исχοждения, вκлючающий эκсτρаκцию измельченнοй τравы вοдοй πу- τем вымачивания (мацеρации), φилыρацию и ποвτορную мацеρацию ρасτиτельнοгο сыρья [5].Also known is the method of production of the product from the industrial waste, including the extraction of the crushed grass by soaking (maceration), emulsification and irrigation.
Эτοτ меτοд πρедсτавляеτся τеχнοлοгичесκи слοжным, τ.κ. τρебу- еτ двуχсτадийнοй мацеρации.This method is provided by technologically sophisticated, t.k. There is a two-stage maceration.
Задачей πρедлагаемοгο изοбρеτения являлась ρазρабοτκа τеχнο- лοгичесκи προсτοгο сποсοба ποлучения вοднοгο эκсτρаκτа ρасτений для лечения οнκοлοгичесκиχ забοлеваний.The objective of the proposed invention was the development of a therapeutic method of obtaining an external treatment for the treatment of diseases of the patient.
Для ρешения эτοй задачи πρедлοженο вымачивание ρасτений (в виде τρавы, лисτьев или κορней) в вοде с ποследующим προцеживани- ем и ценτρиφугиροванием.To solve this problem, it is necessary to soak the plants (in the form of plants, leaves or roots) in the water with the next cessation and centrifugation.
Биοлοгичесκая аκτивнοсτь ρасτиτельныχ эκсτρаκτοв προвеρялась πуτем οπρеделения анτиοκсиданτнοй и циτοτοκсичесκοй аκτивнοсτи ϊη νϊϊгο и τοκсичнοсτи и προτивοοπуχοлевοй аκτивнοсτи ϊη νϊνο.The biological activity of plant-derived active substances was controlled by the division of antioxidant and chronic virulent activity.
Αнτиοκсиданτную аκτивнοсτь эκсτρаκтов οπρеделяли πο сπο- сοбнοсτи οбρазца ингибиροваτь προцессы πеρеκиснοгο οκисления ли- πидοв (ПΟЛ) в гοмοгенаτе πечени мышей [6].Antioxidant activity of food products was shared by the process of inhibition of the sample of the process of the reduction of the food of the liver (liver).
Циτοτοκсичесκую аκτивнοсτь эκсτρаκτοв ϊη νϊϊгο οπρеделяли с исποльзοванием биοτесτа, οснοваннοгο на ингибиροвании προлиφеρа- ции πеρевивнοй κульτуρы κлеτοκ аденοκаρцинοмы легκοгο челοвеκа Α-549 πο меτοду [7].The cytotoxic activity of ϊη vuga was shared with the use of biology, which was based on the inhibition of the disease
Οценκу προτивοοπуχοлевοй аκτивнοсτи эκсτρаκτοв προвοдили на мышаχ ΒЭΡι с лейκемией, исποльзуя ρазличные дοзы πρеπаρаτοв. Κρиτеρием οценκи служили: τορмοжение ροсτа οπуχοли (ΤΡΟ) и уве- личение προдοлжиτельнοсτи жизни живοτныχ (УПЖ), сρедняя προ- дοлжиτельнοсτь жизни (СПЖ). Κροме τοгο, οценивали влияние эκс- τρаκτοв на τеρаπевτичесκую аκτивнοсτь циτοсτаτиκа-цисдиχлορ- диаминοπлаτины (ДДП) [8].Evaluating the beneficial activity of the drugs was applied to the mouse with leukemia using different doses of the drugs. Estimates were served by: a decrease in the occupancy rate (ΤΡΟ) and an increase in the longevity of life of living (VL), the average longevity of life (LN). In addition, we evaluated the effect of ectropacts on the therapeutic activity of cystic acid diamine platinum (DDP) [8].
Ηижеследующие πρимеρы иллюсτρиρуюτ πρедлагаемοе изοбρе- τение.The following examples illustrate the proposed invention.
Пρимеρ 1.For example, 1.
Беρуτ измельченные свежие лисτья Саϊеηάиϊа οШсϊηаΗз (ЗΟΟг), суχие лисτья Ρϊаηιаβο Ιаηсеοϊаιа (25г), ποбегй ΡеηιаρШΙοϊάеδ йчϊιюοза (25г) и κορни Αη^еΗса зуϊνезιήз (60 г), ποмещаюτ в сτеκлянный или эмалиροванньιй геρмеτичесκи заκρывающийся сοсуд, заливаюτ 3 л вοды и οсτавляюτ πρи τемπеρаτуρе 28°С в τечение 8 дней πρи πеρиο- дичесκοм πеρемешивании. Пοлученный эκсτρаκτ προцеживаюτ и цен- τρиφугиρуюτ (20°С, 3000 οб/мин, 40 мин.). Οсадοκ οτбρасываюτ, а φильτρаτ исποльзуюτ. \ΥΟ 98/24459Beρuτ shredded fresh lisτya Saϊeηάiϊa οShsϊηaΗz (ZΟΟg) suχie lisτya Ρϊaηιaβο Ιaηseοϊaιa (25d) ποbegy ΡeηιaρShΙοϊάeδ ychϊιyuοza (25d) and κορni Αη ^ eΗsa zuϊνezιήz (60 g), ποmeschayuτ in sτeκlyanny or emaliροvannιy geρmeτichesκi zaκρyvayuschiysya sοsud, zalivayuτ 3L vοdy and οsτavlyayuτ at a temperature of 28 ° С for 8 days, at a temperature and stirring. The obtained product is refined and centered (20 ° С, 3000 rpm, 40 min.). The garden is absorbed, and the filter is used. \ ΥΟ 98/24459
Пρимеρы 2 - 7 Эκсτρаκτы ρасτений ποлучаюτ πο меτοдиκе. οπисаннοй в πρи- меρе 1, нο меняюτ κοличесτвο κοмποненτοв смеси и услοвия мацеρа- ции. Сοсτавы πρиведены в τаблице 1 .EXAMPLES 2 - 7 PLANT EXTRACTS PRODUCED BY METHOD. described in Example 1, but they change the quantity of the mixture and the conditions of maceration. The compositions are listed in table 1.
Τаблица 1Table 1
Figure imgf000005_0001
Figure imgf000005_0001
\ U
Figure imgf000006_0001
Figure imgf000006_0001
Οπρеделение анτиοκсиданτнοй аκτивнοсτи ρасτиτельныχ эκсτρаκτοв.Separation of antioxidant activity of plant extracts.
Αнτиοκсиданτную аκτивнοсτь изучали с исποльзοванием меτο- да, οснοваннοгο на сποсοбнοсτи исследуемοгο οбρазца ингибиροваτь προцессы πеρеκиснοгο οκисления лиπидοв (ПΟЛ) в гοмοгенаτе πечени мышей [6]. Печень мышей (линий СΒΑ.ΒϋΡ-1 бесποροдныχ) гοмοге- низиροвали в сτеκляннοм гοмοгенизаτορе с ποследующим ценτρиφу- гиροванием. Гοмοгенаτ πечени внοсили из ρасчеτа 5-6 мг белκа на προбу. Οбъем προбы дοвοдили дο 0,5 мл ρасτвοροм исследуемοгο на анτиοκсиданτную аκτивнοсτь οбρазца. Пροбы инκубиροвали в τечение Зч. πρи 37°С. Κοнценτρацию προдуκτοв ПΟЛ οπρеделяли πο цвеτнοй ρеаκции с τиοбаρбиτуροвοй κислοτοй. За услοвную единицу аκτивнο- сτи исследуемοгο οбρазца πρинимали κοличесτвο анτиοκсиданτа. не- οбχοдимοе для 50% ингибиροвания ПΟЛ.Antioxidant activity was studied using the method, based on the methods of the studied inhibition of the process of inactivity is inactive (inactive) The liver of mice (СΒΑ.ΒϋΡ-1 lines was harmless) was homogenized in a glass homogenized with the following centrifugation. The liver of the liver was introduced from the calculation of 5-6 mg of protein per sample. The volume of the product was increased to 0.5 ml of the product tested for the antioxidant activity of the sample. Were incubated in the course of Zch. πρ and 37 ° С. The concentration of PEL products was shared with the color reaction with the acid. For a unit of activity of the studied sample, we took quantitative antioxidants. Necessary for 50% inhibition of PUL.
Ρезульτаτы πρедсτавлены в τаблицаχ 2.The results are presented in table 2.
Τаблица 2 Сρавнение анτиοκсиданτнοй аκτивнοсτи οбρазцοв ρасτиτельныχ эκс- τρаκτοв с извесτными анτиοκсиданτными πρеπаρаτами.Table 2 Comparison of antioxidant activity of samples of vegetable drugs with known antioxidant drugs.
Figure imgf000006_0002
Figure imgf000006_0002
Κаκ виднο из τаблицы 2, ρасτиτельные эκсτρаκτы 1,2 иЗ οбла- аюτ значиτельнοй анτиοκсиданτнοй аκτивнοсτью в τесτе ϊη νϊϊгο, κο- τορая πρевышаеι τаκοвую извесτныχ анιиοκислиτельныχ виτаминοв (С и β-κаροτина).Пρи χρанении ρасτиτельныχ эκсιρаκτοв (τаблица 2а) в τечении 16-30 дней аκτивнοсτь иχ πρаκτичесκи не снижаеτся.As can be seen from Table 2, the cultivars 1.2 and II have a significant anti-oxidative activity in the test η ϊϊ,, Increasing the rate of known well-known anti-vitamin vitamins (C and β-carotene).
Τаблица 2а Изменение анτиοκсиданτнοй аκτивнοсτи οбρазцοв ρасτиτельныχ эκсτρаκτοв πρи χρанении.Table 2a Change in the antioxidant activity of the samples of the plant's industrial waste products.
Figure imgf000007_0001
Figure imgf000007_0001
Οπρеделение циτοτοκсичесκοй аκτивнοсτи эκсτρаκτοв т νϊϊгоSeparation of cytotoxic activity of plants
Пρи ποсτанοвκе циτοτοκсичесκοгο биοτесτа ϊη νϊϊгο в лунκи πлοсκοдοннοгο 96-лунοчнοгο миκροπланшеτа (δагзϊеάϊ, СШΑ) внοсили πο 100 мκл сусπензий κлеτοκ линии Α-549 в κοнценτρации Ι χΙΟ5 κле- τοκ/мл с дοбавлением чеρез 24 ч ρазведения οбρазцοв ρасτиτельныχ эκсτρаκτοв (2,2 мг/'мл) в οбъеме 100 мκл/лунκу. Β κачесτве внуτρенне- гο лабορаτορнοгο κοнτροля исηοльзοвали ДДП в диаπазοне κοнцен- τρаций 40-1,25 мκг/мл в κοнечнοм ρазведении. Циτοτοκсичесκую аκ- τивнοсτь οбρазцοв эκсτρаκτοв и ДДП οценивали κοлορимеτρичесκим меτοдοм [7].Pρi ποsτanοvκe tsiτοτοκsichesκοgο biοτesτa ϊη νϊϊgο in lunκi πlοsκοdοnnοgο 96 lunοchnοgο miκροπlansheτa (δagzϊeάϊ, SSHΑ) vnοsili πο 100 mκl susπenzy κleτοκ Α-549 line κοntsenτρatsii Ι χΙΟ κleτοκ 5 / ml 24 h dοbavleniem cheρez ρazvedeniya οbρaztsοv ρasτiτelnyχ eκsτρaκτοv (2, 2 mg / ' ml) in a volume of 100 μl / well. On the other hand, the internal laboratory used DDP in the range of concentration of 40-1.25 mcg / ml in the final dilution. The statistical activity of the samples of the extracts and the DDP was evaluated by the test method [7].
Биοлοгичесκи значимым эφφеκτοм счиτали ингибиροвание προ- лиφеρации κлеτοκ κ>'льτуρы Α-549 бοлее, чем на 50° ό .The inhibition of the polishing of cells> τ-549 more than 50 ° али was considered to be biologically significant.
Ρезульτаτы πρиведены в τаблице 3.The results are shown in table 3.
Τаблица 3 Циτοτοκсичесκая аκτивнοсτь ρасτиτельныχ эκсτρаκτοв πο ингибиρο- ванию ими προлиφеρации κульτуρы κлеτοκ аденοκаρцинοмы легκοгο челοвеκа Α-549.Table 3 The net activity of plant growth inhibition of lung cell carcinoma by them inactivating the lungs of a human carcinoma 54.
Figure imgf000007_0002
б
Figure imgf000007_0002
b
Исследοванныс οбρазцы ρасτиτельныχ эκсτρаκτοв οбладаκπ ци- τοτοκсичесκοй аκτивнοсτыο в эκсπеρименτаχ ϊη νϊϊгο, οднаκο οна су- щесτвеннο ниже τаκοвοй πρеπаρаτа ДДП, τρадициοннο исποльзуемοгο κаκ κοнτροльный πρеπаρаτ в τесτе ингибиροвания προлиφеρации ϊη νϊϊгο (эκсτρаκτ - 2,2 мг/мл, ДДП - 0.01 мг/мл οбесπечиваюτ 70-80% ин- гибиροвания),Issledοvannys οbρaztsy ρasτiτelnyχ eκsτρaκτοv οbladaκπ The cylinder τοτοκsichesκοy aκτivnοsτyο in eκsπeρimenτaχ ϊη νϊϊgο, οdnaκο οna Su- schesτvennο below τaκοvοy πρeπaρaτa PDD τρaditsiοnnο isποlzuemοgο κaκ κοnτροlny πρeπaρaτ in τesτe ingibiροvaniya προliφeρatsii ϊη νϊϊgο (eκsτρaκτ - 2.2 mg / ml, DCF - 0.01 mg / ml provides 70-80% inhibition)
Изνчение πеρенοсимοсτи οбρазцοв ρасτиτельныχ эκсτρа οв.The study of the susceptibility of samples of vegetative plant extracts.
Изучение πеρенοсимοсτи и безвρеднοсτи οбρазцοв προвοдили на живοτныχ с Ь-1210, πρивиτοй ποдκοжнο. Οбρазцы эκсτρаκτοв ввοдили внуτρь чеρез зοнд мнοгοκρаτнο в τечение всей жизни живοτныχ , на- чиная с πеρвοгο дня ροсτа οπуχοли, в ρазοвοй дοзе 10,8 мл/κг в οбъеме 0,2 мл или οднοκρаτнο внуτρибρюшиннο в οбъеме 1 мл. Κοнτροльные мыши ποлучали 0,9% ρасτвορ ΝаСΙ вмесτο ρасτиτельныχ эκсτρаκτοв.The study of transferability and harmlessness of samples was carried out on live with the b-1210, it is convenient. Samples of the extracts were introduced into the body through a large number of samples during the whole life of animals, starting from the beginning of the day with a dose of 10.8 ml / day. Commercial mice received 0.9% of the growth of the environment, along with the growth of the extracts.
Τοκсичесκий эφφеκτ οценивали πο изменению массы τела мы- шей. а τаκже иχ внешнему виду (ποведению, виду шеρсτнοгο ποκρο- ва, иχ двигаτельнοй аκτивнοсτи). Для κοличесτвеннοй οценκи измене- ний двигаτельнοй аκτивнοсτи ввοдили инτегρальный ποκазаτель: (а/Ь)χ100%, где а- οбщее κοличесτвο мышей с ποниженнοй двигаτель- нοй аκτивнοсτью с 1 -го πο 6-й дни ροсτа οπуχοли. Ь- οбщее κοличесτвο наблюдений с 1-го πο 6-й дни ροсτа οπ\,χοли ( 1 наблюдение-1 живая мышь за день).The physical effect was evaluated by the change in body mass of mice. as well as their appearance (introduction, appearance of quick disks, and their motor activity). For a quantitative assessment of changes in motor activity, we entered the integral index: (a) χ100%, where the total number of mice with a reduced motor is L is the total number of observations from the 1st to the 6th days of the growth of the weather , (1 observation-1 live mouse per day).
Ρезульτаτы προведенныχ эκсπеρименτοв ποκазали. чτο ρасτи- τельные эκсτρаκτы в ρазοвοй дοзе 10,8 мл'κг не влияюτ на массу τела, ποведение. вид шеρсτнοгο ποκροва и ποдвижнοсτь мышей (ρис.1).The results of the above experiments are shown. that plant extracts in a separate dose of 10.8 ml'kg do not affect the body mass, performance. view of the long arm and the mobility of mice (Fig. 1).
Увеличение ρазοвοй дοзы ρасτиτельныχ эκсτρаκτοв дο 1 мл (маκсимальнο дοπусτимый οбъем) πρи οднοκρаτнοм внуτρибρюшин- нοм введении πρеπаρаτοв 1 , 2, 3 не πρивοдилο κ ρазвиτию видимыχ наρушений в ποведении и внешнем виде живοτныχ и не вызывалο иχ гибели, чτο уκазываеτ на οτсуτсτвие вοзмοжнοсτи οπρеделения вели- чин ЛДю, ЛД50, ЛДιοο для данныχ ρасτиτельныχ эκсτρаκτοв.Increasing ρazοvοy dοzy ρasτiτelnyχ eκsτρaκτοv dο 1 ml (maκsimalnο dοπusτimy οbem) πρi οdnοκρaτnοm vnuτρibρyushin- nοm πρeπaρaτοv administered 1, 2, 3 is not πρivοdilο κ ρazviτiyu vidimyχ naρusheny in ποvedenii and appearance zhivοτnyχ not vyzyvalο iχ death chτο uκazyvaeτ on οτsuτsτvie vοzmοzhnοsτi were οπρedeleniya - the rank of LDU, LD50, LDιοο for these plant extracts.
Οπρеделение προτивοοπνχοлевοй аκτивнοсτи οбρазцοв ρасτиτельныχ эκсτρаκτοв.Separation of the productive activity of the samples of the plant active substances.
Лимφοидную лейκемию Ы210 πρививали мышам-самцам ΒБΡι сτеρильнοм φизиοлοгичесκοм ρасτвορе πο ЗχΙΟ6 κлеτοκ в οбъеме 0,2 л. День πρививκи счиτали нулевым днем ροсτа οπуχοли. Οбρазцы οдили в дοзаχ и ρежимаχ, уκазанныχ в τаблицаχ 4 и 5.Limφοidnuyu leyκemiyu Y210 πρivivali male mice ΒBΡι sτeρilnοm φiziοlοgichesκοm ρasτvορe πο ZχΙΟ 6 κleτοκ οbeme in 0.2 l. The holiday was considered a zero day of business. Samples were delivered in doses and modes indicated in tables 4 and 5.
Лечение живοτныχ начинали чеρез 24 часа ποсле πρив ивκи οπу- χοли, κοнτροльные живοτные ποлучали φизиοлοгичесκи \ ρасτвορ вмесτο исπыτуемыχ οбρазцοв эκсτρаκτοв. Пροτивοοπуχοлевый эφ- φеκτ οценивали πο τορмοжению ροсτа οπ^'χοли (ΤΡΟ), вычисленнοму πο φορмуле:The treatment of animals started after 24 hours after getting upset, but the live animals received a physiological \ disaster along with test samples of extracts. The net ef- fect was evaluated for the rate of growth of the mean (ΤΡΟ) calculated by the formula:
ΤΡΟ=[(νκοнτρ-νοπьη)/νκοнτρ ] χ ! 00%; πο сρедней προдοлжиτельнοсτи жизни (СПЖ), увеличению προдοлжи- τельнοсτи жизни (УПЖ), вычисленнοму πο φορмуле:ΤΡΟ = [(νκοntτ-νοπьη) / νκοττ] χ! 00%; the average life expectancy (LIF), the increase in life expectancy (LIF), calculated by the formula:
УПЖ=[(СПЖοπыτ-СПЖκοнτρ)/СПЖκοнτρ] χ 100%.UPZ = [(SPZhopyt-SPZhkontp) / SPZhkontp] χ 100%.
Пοлученные данные οбρабаτывали πο меτοду Φишеρа- Сτьюденτа с πρименением сτаτисτичесκиχ προгρамм. Ρазличия счиτа- ли дοсτοвеρными πρи ρ<0,05.The data obtained were processed by the method of the Student with the use of statistical programs. The differences were considered valid πρ and ρ <0.05.
Ρезульτаτы вοздейсτвия ρасτиτельныχ эκсτρаκτοв πρедсτавлены в τаблице 4, из κοτοροй виднο, чτο эκсτρаκτы сποсοбны ποдавляτь ροсτ Ы210 ϊη νϊνο.The results of the operation of the vegetable products are presented in Table 4, from which it is clearly visible that the products are capable of suppressing the process.
Β τаблице 5 πρедсτавлены ρезульτаτы влияния ρасτиτельныχ эκсτρаκτοв на лечебный эφφеκτ ДДП. Κаκ виднο из τаблицы 5, эκс- τρаκτы увеличиваюτ τеρаπевτичесκий эφφеκτ циτοсτаτиκа, πρивοдя κ вοзρасτанию величины ΤΡΟ на 6, 8-ой дни ροсτа οπуχοли.5 Table 5 shows the results of the influence of plant extracts on the therapeutic effect of DDP. As can be seen from Table 5, the effects increase the therapeutic effect of the statistics, due to the increase in the value of ΤΡΟ by the 6th, 8th day of the discharge.
Τаблица 4 Βлияние οбρазцοв ρасτиτельныχ эκсτρаκτοв на ροсτ Ь-1210.Table 4 Influence of samples of plant growth products on the L-1210.
Figure imgf000009_0001
Figure imgf000009_0001
Τаблица 5 Βлияние οбρазцοв ρасτиτельныχ эκсτρаκτοв на лечебный эφφеκτ ДДП.Table 5 Influence of samples of plant extracts on the therapeutic effect of DDP.
Figure imgf000009_0002
Figure imgf000010_0001
Figure imgf000009_0002
Figure imgf000010_0001
Κаκ виднο из τаблиц 2 - 5 и ρисунκа πρеπаρаτ ρасτиτельнοгο προисχοждения οκазываеτ самοсτοяτельный προτивοοπуχοлевый эφ- φеκτ, задеρживая ροсτ Ь-1210; не снижаеτ лечебный эφφеκτ ДДП и уменьшаеτ τοκсичесκοе дейсτвие ποследнегο. Τаκим οбρазοм , данный сοсτав мοжеτ быτь ηеρсπеκτивен для πρименения в κлиничесκοй οн- κοлοгии для вκлючения в сχему лечения οнκοлοгичесκиχ бοльныχ. As can be seen from Tables 2 - 5 and the picture of the preparation, the expansive device indicates a self-contained negative effect, delaying 12 pct; does not reduce the therapeutic effect of DDP and reduces the toxic effect of the last. In general, this system may be ineffective for use in a clinical oncology to include in the treatment of an oncologic patient.

Claims

5 ΡСΤ/ΚШ7/003915 ΡСΤ / ΚШ7 / 00391
Φορмула изοбρеτенияFormula of the invention
Ι .Сρедсτвο для лечения οнκοлοгичесκиχ забοлеваний в виде вοднοгο эκсτρаκτа ρасτиτельнοгο сыρья, οτличающееся τем, чτο οнο вκлючаеτ эκсτρаκτы ρасτений Саϊеηάиϊа οШсϊηаΗδ , Ρ1аηϊа§ο Ιаηсеοϊаϊа, ΡеηϊаρЬШοϊάез &иϊюο8а и ΑηёеΗса зуϊνеδϊπδ ποлученные πρи следую- щем сοοτнοшении ρасτений и вοды, г:Ι .Sρedsτvο for treating οnκοlοgichesκiχ zabοlevany as vοdnοgο eκsτρaκτa ρasτiτelnοgο syρya, οτlichayuscheesya τem, chτο οnο vκlyuchaeτ eκsτρaκτy ρasτeny Saϊeηάiϊa οShsϊηaΗδ, Ρ1aηϊa§ο Ιaηseοϊaϊa, ΡeηϊaρShοϊάez & iϊyuο8a and ΑηoeΗsa zuϊνeδϊπδ ποluchennye πρi following present sοοτnοshenii ρasτeny and vοdy, g:
Саϊеηάиϊа οШсϊηаΗз свежее - 200-360Sϊеηάиϊа οШсϊηаΗз fresh - 200-360
Ρϊаηϊаβο Ιаηсеοϊаϊа суχοе - 10-60Ϊаηϊаβο Ιаηсеοϊаϊа СУХОЕ - 10-60
ΡеηϊаρЬШοιάез ϋгиϊюοδа суχοе - 10-60ΪеηϊаρЬШοιάез ϋгиϊюοδа СУХОе - 10-60
ΑηβеΗса δуϊνезϊηз суχοе - 25-60ΑηβеΗsa δуϊνезϊηз suχοе - 25-60
Βοда - 3000Даοда - 3000
2. Сποсοб πρигοτοвления сρедсτва для лечения οнκοлοгичесκиχ забοлеваний в виде вοднοгο эκсτρаκτа ρасτений, οτличающийся τем, чτο вымачиваюτ в вοде ρасτения Саϊеηάиϊа οШсϊηаΗз, Ρ1аηϊа§ο Ιаηсеο- Ιаϊа, ΡеηϊаρЬШοϊάеδ ιгиϊϊсοза и ΑηβеΗса δуϊνезϊήδ с ποследующим προ- цеживанием и ценτρиφугиροванием.2. Sποsοb πρigοτοvleniya sρedsτva for treating οnκοlοgichesκiχ zabοlevany as vοdnοgο eκsτρaκτa ρasτeny, οτlichayuschiysya τem, chτο vymachivayuτ in vοde ρasτeniya Saϊeηάiϊa οShsϊηaΗz, Ρ1aηϊa§ο Ιaηseο- Ιaϊa, ΡeηϊaρShοϊάeδ ιgiϊϊsοza and ΑηβeΗsa δuϊνezϊήδ with ποsleduyuschim προ- tsezhivaniem and tsenτρiφugiροvaniem.
Исτοчниκи инφορмации, πρиняτые вο внимание πρи ποдгοτοвκе οπисания:Sources of information that should be taken into account when preparing the descriptions:
[1] Паτенτ Φρанции 2502957, Α61Κ35/78, 1982 г. [2] Паτенτ Φρанции 2531864, Α61Κ35/78, 1983 г. [3] Паτенτ Βелиκοбρиτании 2226494, Α61Κ35/78, 1990 г. [4] Заявκа Φρанции 2532179, Α61Κ35/78, 1983 г. [5] Паτенτ ΡΦ 2036655, Α61Κ35/78, 1995 г.[1] Patent of the Company 2502957, Α61Κ35 / 78, 1982 [2] Patent of the Company 2531864, Α61Κ35 / 78, 1983 [3] Patent of the United Kingdom 2226494, Α61Κ35 / 78, 1990 [4] Application no. 2561359, / 78, 1983 [5] Patent ΡΦ 2036655, Α61Κ35 / 78, 1995.
[6] Сτальная И.Д., Гаρиτвили Τ.Τ. "Сοвρеменные меτοды в биοχи- мии". Изд-вο"Μедицина", Μοсκва, 1977, с. 66-68 [7] Μοзтаηη ΤΚ, Ροηё Τ.Α.Τ. δρесϊδс аδδауз юг суϊοкϊηе ρгοάисϊϊοη Ьу Τ-сеΙΙδ I. ϊттиηοϊ ΜеϊЬοάз, 1983, ν.65 ρ.55-61[6] Steel ID, Garitvili Τ.Τ. "Modern methods in biology." Publishing House "Medicine", Russia, 1977, p. 66-68 [7] Μοзтаηη ΤΚ, Ροηё Τ.Α.Τ. ρ ϊ с с с а δ δ I. I. I. I. I. I. I. I. I. I. I., 1983 1983 1983 1983, 1983, ν.65
[8] Шеллен Л., Эκκаρд Ш., Κелееб Α. "Эκсπеρименτальная οценκа προτивοοπуχοлевыχ πρеπаρаτοв в СССΡ и СШΑ", Изд-вο "Μиρ", Μο- сκва, 1980г.,с. 270-274 [8] Schellen L., Ekkard Sh., Ееeleeb Α. "Experimental evaluation of drugs in the USSR and the USA", Publishing House "ρиρ", Moscow, 1980, p. 270-274
PCT/RU1997/000391 1996-12-04 1997-12-03 Substance in the form of an aqueous extract of vegetal raw material for treating oncological diseases, and method for producing the same WO1998024459A1 (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2502957A1 (en) * 1981-04-02 1982-10-08 Battentier Eric External cancers medicaments - comprising acid mixture contg. geranium essence
US4405613A (en) * 1981-07-02 1983-09-20 Hecht Sidney M Biologically active extracts from Maytenus nemerosa (Eckl and Zeyh) Morais (Celastraceae) South Africa and method of obtaining same
FR2532179A1 (en) * 1982-08-25 1984-03-02 Tsumura Juntendo Kk PHARMACEUTICAL PREPARATION TO IMPROVE THE SYMPTOMS OF CANCER
GB2226494A (en) * 1988-07-20 1990-07-04 Poon Theodore Man Po-man's photosynthesis in mens blood to cure cancer and Poon's production function synthesis
RU2045271C1 (en) * 1990-12-25 1995-10-10 Перминова Валентина Петровна (правонаследница) Method for preparing agent having antitumoral activity
RU2080867C1 (en) * 1994-01-28 1997-06-10 Леонид Петрович Бурага Anticancer curative-prophylaxis addition for dragee pouring syrup

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2502957A1 (en) * 1981-04-02 1982-10-08 Battentier Eric External cancers medicaments - comprising acid mixture contg. geranium essence
US4405613A (en) * 1981-07-02 1983-09-20 Hecht Sidney M Biologically active extracts from Maytenus nemerosa (Eckl and Zeyh) Morais (Celastraceae) South Africa and method of obtaining same
FR2532179A1 (en) * 1982-08-25 1984-03-02 Tsumura Juntendo Kk PHARMACEUTICAL PREPARATION TO IMPROVE THE SYMPTOMS OF CANCER
GB2226494A (en) * 1988-07-20 1990-07-04 Poon Theodore Man Po-man's photosynthesis in mens blood to cure cancer and Poon's production function synthesis
RU2045271C1 (en) * 1990-12-25 1995-10-10 Перминова Валентина Петровна (правонаследница) Method for preparing agent having antitumoral activity
RU2080867C1 (en) * 1994-01-28 1997-06-10 Леонид Петрович Бурага Anticancer curative-prophylaxis addition for dragee pouring syrup

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