WO2005058333A1 - Procede pour obtenir un serum sanguin biologiquement actif et traite par electrochocs et son utilisation - Google Patents

Procede pour obtenir un serum sanguin biologiquement actif et traite par electrochocs et son utilisation Download PDF

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Publication number
WO2005058333A1
WO2005058333A1 PCT/EP2003/014578 EP0314578W WO2005058333A1 WO 2005058333 A1 WO2005058333 A1 WO 2005058333A1 EP 0314578 W EP0314578 W EP 0314578W WO 2005058333 A1 WO2005058333 A1 WO 2005058333A1
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Prior art keywords
cells
line
blood
blood serum
serum
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PCT/EP2003/014578
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German (de)
English (en)
Inventor
Vitali Alexandrovich Shestakov
Christoph Hanz
Original Assignee
Owen Holding Ltd
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Publication date
Application filed by Owen Holding Ltd filed Critical Owen Holding Ltd
Priority to PCT/EP2003/014578 priority Critical patent/WO2005058333A1/fr
Priority to AU2003298215A priority patent/AU2003298215A1/en
Priority to AU2004299279A priority patent/AU2004299279B2/en
Priority to CA002546979A priority patent/CA2546979A1/fr
Priority to RU2006121488/15A priority patent/RU2364404C2/ru
Priority to CN2004800376828A priority patent/CN1893961B/zh
Priority to JP2006544384A priority patent/JP2007514706A/ja
Priority to PCT/EP2004/014510 priority patent/WO2005058889A2/fr
Priority to BRPI0417797-5A priority patent/BRPI0417797A/pt
Priority to EP04804108A priority patent/EP1699470A2/fr
Publication of WO2005058333A1 publication Critical patent/WO2005058333A1/fr
Priority to IL176343A priority patent/IL176343A0/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/16—Blood plasma; Blood serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention belongs to medicine and is used to obtain a biologically active and electroshocked blood serum which is useful in some diseases and disorders of the human and animal organism (energy change and cyclic adenosine monophosphoric acid content in brain tissue, long-term memory, epilepsy, etc.) )
  • a biologically active and electroshocked blood serum which is useful in some diseases and disorders of the human and animal organism (energy change and cyclic adenosine monophosphoric acid content in brain tissue, long-term memory, epilepsy, etc.)
  • the use of the blood serum according to the invention for regulating the proliferation of different human tumor cells is also treated.
  • a method for obtaining an active substance from blood serum is known, which is based on the extraction of blood from humans and animals, the incubation and the secretion of the active substance with subsequent preservation.
  • This method involves obtaining a blood serum that increases the body's resistance to exogenous and endogenous factors such as air pressure, air temperature, gravity, light etc. as well as hunger, thirst, sleep and sexual needs etc. (see JP 2123287, EP 0 542 303; RU 2096041, RU 2120301).
  • the blood serum is taken from a donor who has previously been put into a certain functional state. Depending on the degree of exposure, blood serum with different biological activity is obtained, namely with miogenic, somnogenic, ophthalmogenic, audioactive, thermoactive, dietary, sexually active, anti-hypoxic, anti-alcohol and anti-nicotine activity.
  • the present invention represents a further development of these methods and deals with the different uses of the blood serum obtained.
  • such peptides such as the parathyroid peptide, gastrin, bombezin promote the development of tumor cells and the development of breast, bone and colon cancer [sh. Kitazawa S., Maeda S., Development of skeletal metastases // Clin. Orthop, 1995, v. 312, p. 45-50; Kaji et al. Carbokyl - termmal peptices from parathyroid hormone-related protein stimulate osteoclast - like cell formation // Endocrinology, 1995, V. 136, P. 842-847].
  • the aim of the present invention is to provide a new method for obtaining a biologically active blood serum from chicken blood.
  • Another aspect of the present invention is the development of a drug form for a new, biologically active blood serum.
  • the invention is based on various pharmaceutical forms: inter alia peroral, parenteral, nasal and buccal administration and in the form of suppositories and similar types.
  • the invention provides for the use of suitable and physiologically acceptable media (such as distilled water) and fillers (e.g. cocoa butter).
  • suitable and physiologically acceptable media such as distilled water
  • fillers e.g. cocoa butter
  • the biologically active blood serum treated with electroshock can be used both independently and in conjunction with other biologically active agents.
  • An additional object of the invention is a pharmaceutical composition in which the active substance according to the present invention acts as an agent.
  • the pharmaceutical composition must have an active ingredient in an amount sufficient to have a beneficial effect on the patient's organism, i.e. an effective amount.
  • Another object of the invention is to determine the effective dose of the active substance according to the present invention. This dose is presumably in the range from 95 to 105 mg / kg of body weight of the patient. The treating doctor should therefore determine the specific dose based on the patient's condition, age, weight and type of treatment.
  • Another object of the invention is the use of the blood serum according to the invention for regulating the proliferation of different human tumor cells.
  • the following cells were used: cells from the Jurkat line of human T cell lymphoma, cells from the Raj line of human B cell lymphoma, cells from the Bro line of human melanoma cells, cells from the HeLa line of cervical cancer, cells from the adenocarcinoma of the mammary gland MCF-7 line, cells of the Mg63 line and fibrosarcoma of the HT1080 line, cells of the IMR-32 neuroblastoma and hepatocarcinoma of the HepG2 line.
  • lymphoid cells Jurkat and Raj
  • epitheloid cells HeLa and MCF-7
  • cells of neuronal origin IMR-32
  • cells of the connective tissue Mg63 and HT1080
  • mesenchymal cells HepG2
  • the electro shock Il.bis III. Degree-treated chicken blood (electrical current 80-120 volts, frequency 50 Hertz, current 0.05 amps, exposure time: 3-4 seconds in the head area).
  • the blood was taken from the carotid artery and subsequently incubated at 4-8 ° C for 18-24 hours in polyethylene jars. After complete blood clot retraction, the vials were held at 3000 rpm for 20-30 minutes. centrifuged, the serum was separated from blood clots and lyophilized under normal conditions.
  • the vials with the lyophilized serum were irradiated on RZ-100 M systems at 20 to 30 kGy, preferably at about 25 kGy, using Co.
  • the serum obtained in this way was stored at a temperature of 4-8 ° C.
  • the experiments were carried out on rats of the Wistar line, namely males with a body mass of 280-300 g.
  • the animals were divided into 4 groups of 10 rats each.
  • the rats were given 1.0 ml of the physiological solution.
  • the rats of the second group were administered serum in a dose of 100 +/- 5.0 mg / kg of body weight (1.0 ml in volume).
  • the rats were decapitated 30 minutes after the injection.
  • the rats of the third group were given 1.0 ml of the physiological solution and the rats of the fourth group were given serum (100 +/- 5.0 mg / kg body weight) in a volume of 1.0 ml. 30 minutes after the injection, the Animals with a weight attached to the tail (10% of the body weight of the rat) are placed in a container with water (25 ° C). After the first signs of agony, the animals were removed from the water and decapitated.
  • the brain, heart, liver (as organs with an intense energetic overload in processes of extreme adaptation) and the skeletal muscles (as the main carrier organ) were used as patterns.
  • the tissue patterns of each rat were weighed, cooled with an isotonic NaCl solution and quickly frozen with liquid nitrogen. The total time of "loading" until the end of sampling was max. 5-6 minutes.
  • Adenosine triphosphoric acid, adenosine desophosphoric acid and adenosine monophosphoric acid were determined in the skeletal muscles of the rats. Nucleotides were separated on columns using ion exchange chromatography using Dowex 1 anionite. The quantitative determination of the adenosine triphosphoric acid, adenosine desophosphoric acid and adenosine monophosphoric acid content was carried out spectrophotometrically (spectrophotometer Hitachi-557) within a range of 256 Nm.
  • the energy potential was calculated using the following formula:
  • the amount of cyclic adenosine monophosphoric acid in the brain, heart and liver was determined by radioimmunological analysis using a special device from Amersham (Great Britain).
  • the marked adenosine monophosphoric acid was determined using the scintillator computer GS-8.
  • adenosine triphosphoric acid adenosine desophosphoric acid and adenosine monophosphoric acid and the increase in the energy potential are both when comparing the third group with the control group and the second group (p ⁇ 0.05) as well as the fourth group with the control group and the second group (p ⁇ 0.05) as well as when comparing the third and fourth groups with each other (p ⁇ 0.05 Table 1).
  • Table 1 Content of adenosine triphosphoric acid, adenosine desophosphoric acid and adenosine monophosphoric acid and the energy potential in the tissue of the skeletal muscles after electroshock-treated serum
  • adenyl system values when awake and 30 minutes after slight stress due to the injection confirm that under the influence of serum the mixing of the levels of adenosine triphosphoric and adenosine desophosphoric acid in the muscle tissue takes place to the upper standard values, while the adenosine monophosphoric acid content is directed downwards.
  • the electroshock-treated serum increases the energy potential in the skeletal muscle tissue of the rat, promotes the increase in the content of cyclic adenosine monophosphoric acid in the brain tissue both at rest and under extreme conditions physical exertion and, after physical stress in the rats, favors the increase in cyclic adenosine monophosphoric acids in the heart and liver tissue.
  • rats were placed in a cylinder which was located in a thermostatic vessel filled with water.
  • the cylinder set up on three supports, allowed the animals to dive under its lower edge and reach the platform outside the cylinder.
  • the electroshock-treated serum was injected into the abdominal cavity at a dose of 100 mg / kg body weight 30 minutes before the start of the experiment.
  • the control animals were given 1 ml of the physiological solution. The next day the reflex behavior was tested, after which there was a 42-day break.
  • 30 animals that had been taught how to dive under a "bell" for five days were divided into three groups.
  • the animals of the first group (10 rats) were injected with cytisine (H-cholinoceptive-B looseness of the brain) in the form of a physiological solution at a dose of 1 mg / kg body weight 30 minutes before the test.
  • the third group of animals (control - 10 rats) was injected with a physiological solution in a dose of 1 ml.
  • the complex behavior of the animals was tested 48 hours after the injection of the substances mentioned using the above method.
  • the bioassay showed 48 hours after the effects of cytisine were noticeable, a marked slowdown in the "escape response" from a closed room, that is three times as compared to the control animals.
  • Preliminary administration of the serum until the cytisine injection not only abolished the action of this blocker, but also caused a 20% increase in "escape” response compared to the control group, and the overall efficacy of the substance exceeded that of the blocker 5 times (Table 5).
  • the blood serum treated with electroshock therefore promotes the formation of long-term memory, especially in animals with a slow "escape reaction” from a closed room and from water. It also plays an important role in maintaining long-term memory via the H-cholinoceptive brain mechanisms.
  • camphor in toxic doses causes hyperactivation of the moving areas of the central nervous system, which in turn is reflected in the development of tonic cramps. For this reason, camphor is used in addition to Korazol for the generation of cramps. Depending on the dose of the preparation administered, camphor is used to produce all the typical components of a small and large epileptic seizure.
  • the blood serum according to the invention is a lyophilized, with electroshock II. - III. Grade treated chicken blood serum [Beresnjewa W.I., "Electrical trauma, electrical combustion and treatment", M., 1964, p. 87]. Two types of these were used in the tests: the first - dissolved in water at a concentration of 100 mg / ml (test fraction 1), the second - after centrifuging the suspension at 10,000 x g for three minutes (three minutes) (test fraction 2).
  • the cells of the Jurkat and Raji lines and lymphocytes of the human peripheral blood were placed in plastic plates (Nunc or Falcon) in 1640 RPMI medium (Sigma) by adding the 10% bovine fetal serum (Gibco), 100 units / ml penicillin and 100 ⁇ g / ml streptomycin at a room temperature of 37 ° C in a CO incubator with 5% CO 2 content and cultured at 95% humidity.
  • Bro, HeLa, MCF-7, Mg63, HT1080, IMR-32 and HepG2 lines were also cultured, but in DMEM medium (Sigma).
  • a 15 ml Phykoll-Pak solution is poured into two 50 ml conical test tubes (Falcon), after which 25 ml of blood diluted twice in a phosphate salt buffer (PSP) are applied.
  • the test glasses are then spun in a baket rotor at 400 x g and 20 ° C for 30 minutes.
  • the upper phase, which contains plasma, is not used.
  • the evaluation of the biosynthetic intensity DNA was carried out after the addition of 3 H-thymidine to the acid-insoluble cell fraction.
  • lymphocytes were cultivated in 96-well plates in 200 ul medium with 200-800 thousand medium in each well in the full medium with different concentrations of the test substance.
  • 3 H-thymidine (1 ⁇ Ki / well, 40 mKi / mmol) was added 2 hours before the end of the incubation.
  • the cells were collected on filters using an automatic device for cell collection, the acid-soluble products were washed with 5% TH-acetic acid (H 2 O) and their radioactivity was measured with a scintillometer.
  • the biosynthesis intensity DNA is in imp./min. measured.
  • the cells were collected in a logarithmic growth phase (adhesive cells if they fill approximately half an area of the nutrient plate), placed in the nutrient medium, in the Gorjaew chamber) and then counted in a nutrient medium with a concentration of 50-100,000 dissolved in 1 million.
  • the cell solution was added to the 96-well plates after adding different concentrations of the test substances, each 100 .mu.l.
  • 50 ⁇ l of MTT solution in the nutrient medium (3-4,5-dimethylthiazol-2-yl) -2.5 diphenyl tetrazolium bromide were added to all waves after the incubation in various 96-wave columns in all waves.
  • MTT solution 1 ml of MTT starting solution is mixed with 4 ml of nutrient medium.
  • the MTT final solution is prepared by dissolving this substance in a phosphate salt solution (PSL, 0.01 M sodium phosphate buffer pH 7.4, with a 0.15 M NaCl content) with a concentration of 5 mg MTT / ml PSL and further filtering a filter with a pore diameter of 0.45 ⁇ m (storage takes place at a temperature of + 4 ° C for up to one month).
  • PSL phosphate salt solution
  • a filter 0.45 ⁇ m
  • the nutrient medium is removed by suction with the pump, 150 ⁇ l of dimethyl sulfoxide (DMSO) are added to each well to dissolve the blue formazan crystals formed, and the optical density of the solution in each well on a multi-channel spectrophotomer for microplates at a wavelength of 540 nm measured (lab system).
  • DMSO dimethyl sulfoxide
  • the results of the viability of the cells depending on the concentration of the substance are shown in percent of the survival of the control cells.
  • the data were processed with the "Origin" computer program. Results and discussion The results are shown in Figures 1 - 8. This results in the following: the highly concentrated substance S1 (2.5-20 mg / ml) has an inhibitory effect on all cells, but the reaction of cells of different tissue types to this substance is different.
  • the IC50 dose (concentration of the substance that leads to 50% inhibition of the cells) varies for different cell lines from 2.2 (Jurkat) to> 20 mg / ml (Mg63) for the starting substance (Index 1) from 3.6 ( Peripheral blood lymphocytes) up to> 20 mg / ml (Mg 63 and HeLa) for the soluble fraction of the substance (index 2).
  • the toxicity of the starting substance was higher than that of the soluble substance.
  • the toxicity of these forms was almost the same (Mg63, Raji, lymphocytes of peripheral blood), and for others (Jurkat, MCG-7, LMR-32) there were 2-3 according to IC50 - major differences.
  • Table 7 Sensitivity of the tested cell lines to the preparation "Doxorubizin"
  • test substance has mitogenic activity, ie an ability to stimulate lymphocyte proliferation (in this case its increase in volume, which is usually due to the enhancement of the biosynthesis of DNA lymphocytes, which is assessed for the presence of 3 H-thymidine) is detected).
  • test substance has a toxic effect on lymphocytes (is mostly assessed after the inhibition of lymphocyte proliferation, which was previously stimulated by mitogens with 3 H-thymidine content or with the help of vital MTT-type dyes).
  • non-activated lymphocytes do not proliferate in the culture and that their number increases under the influence of mitogens as the mitogen concentration increases. This is expressed in the increase in the marked DNA.
  • Section (1) reflects the range of the mitogen concentration in which the increasing effect (the biosynthetic intensity DNA) is in relation to the mitogen concentration.
  • the second section of the curve (2) shows the flat section again and contains the range of the mitogen concentration, namely when the highest effect has already been achieved, the increase in the mitogen concentration is not characterized by a change in the proliferation level reached and no cytotoxic effect is observed.
  • Section (3) shows the range of the mitogen concentration in which it already has a toxic effect.
  • the subject of the investigation was the effect of the substance on the non-activated lymphocytes of the human peripheral blood.
  • the dependence of the proliferative activity (effectiveness) on the dose of the substance was tested.
  • the subject of the tests carried out was the effect of the substance on the biosynthetic intensity DNA of the lymphocytes (FHA 20 ⁇ g / ml) activated by phytohemaglytinyl in the second phase.
  • the number of peripheral blood lymphocytes has not changed significantly.
  • the effectiveness of the substance was examined for the lymphocytes activated with Mitogen FHA 20 ⁇ kg / ml, the inhibition of the activated lymphocytes was found.
  • the cytotoxic activity of the substance was also examined by adding to the cells the carcinoma of the mammary gland of the MCF-7 line, which is in the state of a monomolecular layer. No proliferation was found due to contact braking of the cells. With such a model one can determine the toxic effect of the substance, i.e. separate them from the cytostatic activity. When using this model, it has been found that the substance has its own cytotoxic effect at a concentration above 2.5 mg / ml, regardless of whether the insoluble fraction has been removed or not. However, the dependence on the dose is very weak.
  • the toxic effect is significantly weaker, which may be related to the fact that an effect was registered within 24 hours and not after 72 hours, as is the case with the proliferated cells (A prolonged cell incubation in the state of a monomolecular layer can lead to the death of the control cells).
  • test substance not only has a cytostatic effect, but also its own cytotoxic activity.
  • cytotoxic activity was significantly lower than the total cytotoxic and cytostatic activity, although these were observed at the same concentration.
  • Grade S1 obtained in the dosage 0.1-1.1 mg / ml causes 10-40% higher proliferation of the human cells of the Jurkat, Raji, Bro, Mg63, HT1068 and HegL2 lines than those of the control group.
  • the substance used in higher doses (2.5 - 20 mg / ml) have a noticeable inhibition of the proliferation of all of the human cancer cells that we examined.
  • the sensitivity of the cells to the substance S1 is significantly higher than to the known anti-tumor preparation doxorubizine.
  • the substance has both a cytostatic and a cytotoxic effect.

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Abstract

L'invention concerne le domaine médical et l'obtention d'un sérum sanguin biologiquement actif et traité par électrochocs, ce sérum s'avérant utile dans le cas de certaines maladies et de certains troubles de l'organisme humain ou animal (variations énergétiques et teneur en acide adénosine monophosphorique cyclique dans le tissu cérébral, épilepsie, etc.). La présente invention porte également sur l'utilisation du sérum sanguin de l'invention pour réguler la prolifération de différentes cellules tumorales humaines.
PCT/EP2003/014578 2003-12-18 2003-12-18 Procede pour obtenir un serum sanguin biologiquement actif et traite par electrochocs et son utilisation WO2005058333A1 (fr)

Priority Applications (11)

Application Number Priority Date Filing Date Title
PCT/EP2003/014578 WO2005058333A1 (fr) 2003-12-18 2003-12-18 Procede pour obtenir un serum sanguin biologiquement actif et traite par electrochocs et son utilisation
AU2003298215A AU2003298215A1 (en) 2003-12-18 2003-12-18 Method for obtaining a biologically active blood serum treated with electroshock and the utilization thereof
CN2004800376828A CN1893961B (zh) 2003-12-18 2004-12-20 通过电刺激获得的生物活性血清
CA002546979A CA2546979A1 (fr) 2003-12-18 2004-12-20 Serum sanguin actif biologique, procedes de production de ceserum et utilisations correspondantes
RU2006121488/15A RU2364404C2 (ru) 2003-12-18 2004-12-20 Биологически активная сыворотка крови, способы ее получения и ее применение
AU2004299279A AU2004299279B2 (en) 2003-12-18 2004-12-20 Biological active blood serum obtained by electrostimulation
JP2006544384A JP2007514706A (ja) 2003-12-18 2004-12-20 生物学的活性血清、その製造方法および使用
PCT/EP2004/014510 WO2005058889A2 (fr) 2003-12-18 2004-12-20 Serum sanguin actif biologique, procedes de production de ce serum et utilisations correspondantes
BRPI0417797-5A BRPI0417797A (pt) 2003-12-18 2004-12-20 soro sangüìneo biologicamente ativo, métodos para produzi-lo e seus usos
EP04804108A EP1699470A2 (fr) 2003-12-18 2004-12-20 Serum sanguin biologiquement actif obtenu par electrostimulation
IL176343A IL176343A0 (en) 2003-12-18 2006-06-15 Biological active blood serum obtained by electrostimulation

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PCT/EP2003/014578 WO2005058333A1 (fr) 2003-12-18 2003-12-18 Procede pour obtenir un serum sanguin biologiquement actif et traite par electrochocs et son utilisation

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007065714A1 (fr) * 2005-12-09 2007-06-14 Owen Holding Ltd. Procédé servant à obtenir une fraction biologiquement active de sérum sanguin traité avec une irradiation gamma et son utilisation
CN115261321A (zh) * 2022-09-27 2022-11-01 北京大学口腔医学院 增强t淋巴细胞抗肿瘤功能的方法及用途

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108348624B (zh) * 2015-08-04 2021-07-27 瓦克星治疗有限责任公司 基于细菌小细胞的生物药物的电离辐射灭菌以及使用方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1283047A1 (fr) * 2000-02-29 2003-02-12 Vitaly Alexandrovich Shestakov Procede de production d'une substance biologiquement active a partir du serum sanguin

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1283047A1 (fr) * 2000-02-29 2003-02-12 Vitaly Alexandrovich Shestakov Procede de production d'une substance biologiquement active a partir du serum sanguin

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007065714A1 (fr) * 2005-12-09 2007-06-14 Owen Holding Ltd. Procédé servant à obtenir une fraction biologiquement active de sérum sanguin traité avec une irradiation gamma et son utilisation
EP1797890A1 (fr) * 2005-12-09 2007-06-20 OWEN Holding LTD Procédé pour obtenir une fraction biologiquement active du serum traitée par irradiation gamma et son utilisation
CN115261321A (zh) * 2022-09-27 2022-11-01 北京大学口腔医学院 增强t淋巴细胞抗肿瘤功能的方法及用途
CN115261321B (zh) * 2022-09-27 2022-12-27 北京大学口腔医学院 增强t淋巴细胞抗肿瘤功能的方法及用途

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CN1893961B (zh) 2010-09-22
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