JPS6323175B2 - - Google Patents

Description

[Detailed description of the invention]

INDUSTRIAL APPLICATION FIELD The present invention relates to a prophylactic and therapeutic agent for disseminated intravascular coagulation (hereinafter referred to as DIC). More specifically, the present invention relates to Streptococcus pyogenes (group A type 3), which is commercially available from Chugai Pharmaceutical Co., Ltd. under the registered trademark "Picibanil".
This invention relates to a prophylactic/therapeutic agent for DIC, which is a prophylactic/therapeutic agent for disseminated intravascular coagulation syndrome, which is a host function-activating/anti-malignant tumor lytic streptococcal preparation consisting of a freeze-dried powder treated with Su strain penicillin. Conventional technology In DIC, the coagulation system is activated within the blood vessels and many microthrombi are formed in small blood vessels throughout the body, resulting in the decomposition of coagulation factors such as platelets, fibrinogen, prothrombin, factor No. It is a general term for a syndrome in which blood clots cause coagulopathy, and when the appearance of anticoagulant factors also causes significant bleeding (for example, as described in "Clinica" No. 4, published in 1978, pages 292-296) ``Pathology of Intravascular Coagulation Syndrome'' by Kenzo Tanaka). Various organs, especially the kidneys, heart,
It has also been reported that necrotic foci (particularly due to diffuse ischemic degeneration) occur in the brain, pituitary gland, etc., resulting in dysfunction of these organs. [For example, “A.M.G.A.” published in 1976 (Showa 42)
Margarethen D'Avrill (Am. J.
“Damage in disseminated” by Margaretten W.
In recent years, emphasis has been placed not only on the mere formation of microthrombi but also on the occurrence of tissue damage caused by this (the above two documents and others). Heparin was used exclusively, and nothing else could be used clinically.However, this heparin
Although it is effective as a symptomatic treatment used after DIC occurs, it has no significant preventive effect. For this reason,
It was hoped that a drug with a significant DIC preventive effect would be developed. Problems to be Solved by the Invention The present invention has a DIC preventive effect, and also has a DIC prevention effect.
Superior to heparin as a symptomatic treatment agent
The aim is to provide drugs for preventing and treating DIC. Means for Solving the Problems In order to achieve the above object, the present invention provides a DIC preventive/therapeutic agent comprising the streptococcal preparation picibanil. Picibanil (registered trademark of Chugai Pharmaceutical Co., Ltd.) used in the present invention is a
Streptococcus pyogenes (group A type 3) Su strain is known as a host function-activating, anti-malignant tumor lytic streptococcal preparation consisting of penicillin-treated freeze-dried powder [Beta-hemorytectus Streptococcus asu, written by Okamoto, H. et al. Acancer Controller “β-Hemolytic
streptococcus as a cancer controller)”
published by Chugai Pharmaceutical Co., Ltd. in 1972], but there are no reports regarding its application to DIC. Picibanil is commercially available from Chugai Pharmaceutical Co., Ltd., and is also published in known literature such as Sakurai Y.
(Sakurai, Y.) “Tumor-inhibitory effect of streptococcal preparation”
Streptococcus pyogenes (group A type 3) as described in Part 1, vol. 56, No. 1 of Cancer Chemotherapy Reports published in February 1972. It is easily produced by culturing Su strain and treating it with penicillin G. The DIC preventive/therapeutic agent of the present invention can be administered in various dosage forms, oral and parenteral.In the case of oral administration For example, oral solid preparations such as tablets, coated tablets, granules, powders, and capsules; oral liquid preparations such as syrups, dry syrups, and elixirs; and in the case of parenteral administration, for example, It can be administered as an injection or a rectal suppository.Any of these preparations can be prepared by a conventional method.More specifically, oral solid preparations such as tablets and capsules include gum tragacanth, gum arabic, corn starch, or gelatin. Binders such as, excipients such as microcrystalline cellulose, leavening agents such as corn starch, pre-gelatinized starch, alginic acid, lubricants such as magnesium stearate, sweeteners such as sucrose, lactose or aspartate, peppermint. , flavoring agents, such as red bean oil or cherries, and, when the dosage unit form is a capsule, a liquid carrier such as an oil or fat may also be included.
Various other materials may be present as coatings or to otherwise modify the physical form of the dosage unit. For example, tablets are Sierra Tsuk,
Can be coated with sugar or both. Oral liquid preparations such as syrups, dry syrups, and elixirs may contain sucrose as a sweetening agent, methyl or propylparaben as a preservative, dyes, and flavoring agents such as cherry or orange flavor. . Sterile compositions for injection include Picibanil (registered trademark of Chugai Pharmaceutical Co., Ltd.) in a vehicle such as distilled water for injection, or in a natural vegetable oil such as sesame oil, coconut oil, fallen seed oil, cottonseed oil, etc. They can be formulated according to conventional formulations by dissolving or suspending them in synthetic resin vehicles such as ethyl oleate and the like. Buffers, preservatives, antioxidants, etc. can also be added as necessary. When preparing rectal suppositories, excipients and, if necessary, a surfactant may be added, and then the suppositories may be prepared by a conventional method. The dosage of the DIC preventive/therapeutic agent of the present invention varies depending on the symptoms, body weight, age, etc. of the subject to be administered, and is determined clinically by each physician in charge. 0.001~10 per time
The desired effect can be achieved by administering mg daily or once every few days. In addition, picibanil, the main drug of the DIC prevention/treatment agent of the present invention, has a LD ₅₀ in mice (intraperitoneal administration).
is 125mg/Kg [Chugai Pharmaceutical Co., Ltd., basic report,
(1969)], it is a safe substance. The DIC preventive/therapeutic effect of the DIC preventive/therapeutic agent of the present invention was confirmed by the following experimental example. Experimental example Escherichia coli-derived lipopolysaccharide (hereinafter referred to as "LPS")
Experimental DIC was induced in rats by intraperitoneal administration of DIC, and the presence or absence of the DIC preventive/therapeutic effect of the DIC preventive/therapeutic agent of the present invention on this pathological condition was evaluated using platelet count (PLT), fibrinogen amount (Fbg), prothrombin time ( PT) and partial thromboplastin time (PTT). 1 Measurement sample preparation Picibanil (OK-432 Note, Chugai Pharmaceutical Co., Ltd.)
(manufactured by Difco, USA), LPS (E.
E. coli (E. coli 0127:B-8) in sterile physiological saline solution in 5 8-week-old Wistar male rats (180 ± 6 g) per experimental group.
was administered intraperitoneally. The order of administration is as follows. Experiment (1): In order to measure the DIC treatment effect of the DIC preventive/therapeutic agent of the present invention, LPS (5 mg/Kg) and picibanil (5 mg/Kg) were simultaneously administered intraperitoneally. Experiment (2): In order to measure the DIC preventive effect of the DIC preventive/therapeutic agent of the present invention, pisibanil (0.05 mg/Kg) was first administered intraperitoneally, and 24 hours later, LPS (5 mg/Kg) was intraperitoneally administered. administered. In both experiments, rats were anesthetized with ether 5 hours after LPS administration, and blood was collected from the heart. A sample was prepared by adding 1 volume of 3.8% sodium citrate to 9 volumes of blood (citrate-added blood). 2 Measurement method (1) PLT coefficient Platelet-rich plasma was prepared by subjecting citrate-added blood to centrifugation at 800 rpm for 15 minutes, and the platelet count was calculated using a platelet counter. (2) Measurement of Fbg, PT, and PTT Plasma was prepared by centrifuging citrated blood at 3000 rpm for 20 minutes. ) (manufactured by Bering Institute, West Germany), and PTT was measured using Pathromtin (same as above). 3. Measurement results The results of (1) and (2) are shown in the following table as the average values of 5 animals in each experimental group. In the table, the control group column shows the results when only sterile physiological saline was administered.

【table】

[Table] The results of experiment (1) indicate the DIC treatment effect of the DIC preventive/therapeutic agent of the present invention, and the results of experiment (2) indicate the DIC
It shows remarkable preventive effect. Effects of the Invention As described above, the present invention provides an extremely excellent preventive/therapeutic agent for DIC.

Claims (1)

[Claims] 1 Streptococcus pyogenes (group A 3
A preventive/therapeutic agent for disseminated intravascular coagulation syndrome consisting of a host function-activating anti-malignant tumor streptococcal preparation consisting of a freeze-dried powder treated with penicillin (type) Su strain.''