HRP960345A2 - Use of ipriflavone to reduce the number of cd8+ cells - Google Patents
Use of ipriflavone to reduce the number of cd8+ cells Download PDFInfo
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- HRP960345A2 HRP960345A2 HRP9502198A HRP960345A HRP960345A2 HR P960345 A2 HRP960345 A2 HR P960345A2 HR P9502198 A HRP9502198 A HR P9502198A HR P960345 A HRP960345 A HR P960345A HR P960345 A2 HRP960345 A2 HR P960345A2
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- SFBODOKJTYAUCM-UHFFFAOYSA-N Ipriflavone Chemical compound C=1C(OC(C)C)=CC=C(C2=O)C=1OC=C2C1=CC=CC=C1 SFBODOKJTYAUCM-UHFFFAOYSA-N 0.000 title claims description 13
- 229960005431 ipriflavone Drugs 0.000 title claims description 12
- 210000004698 lymphocyte Anatomy 0.000 claims description 12
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 4
- 230000001629 suppression Effects 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 238000001802 infusion Methods 0.000 claims description 2
- -1 infusion Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 19
- 231100000433 cytotoxic Toxicity 0.000 description 15
- 230000001472 cytotoxic effect Effects 0.000 description 15
- 230000008105 immune reaction Effects 0.000 description 10
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000007423 decrease Effects 0.000 description 9
- 238000011282 treatment Methods 0.000 description 8
- 230000009467 reduction Effects 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 210000002443 helper t lymphocyte Anatomy 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012645 endogenous antigen Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 230000003262 anti-osteoporosis Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 244000000056 intracellular parasite Species 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000009993 protective function Effects 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Description
Predmetni izum se odnosi na farmaceutske spojeve prikladne za smanjivanje broja CD8+ stanica koje sadrže 7-izopropoksilizoflavon (IPRIFLAVON) kao aktivni sastojak. The present invention relates to pharmaceutical compounds suitable for reducing the number of CD8+ cells containing 7-isopropoxyisoflavone (IPRIFLAVON) as an active ingredient.
IPRIFLAVON je poznato antiosteoporotsko sredstvo. Njegova priprema je opisana u specifikacijama mađarskih patenata br. 162377 i 196981. Poznato je da organizam ima dvije osnovne zaštitne funkcije, humoralnu i stanično vezanu imuno reakciju. Takozvana stanično vezana imuno reakcija je primarno usmjerena protiv endogenih antigena na stanicama inficiranim virusom ili intracelularnim parazitom, stanicama tumora, kemijski modificiranim stanicama i stranim tkivima. IPRIFLAVON is a known anti-osteoporotic agent. Its preparation is described in the specifications of Hungarian patents no. 162377 and 196981. It is known that the organism has two basic protective functions, humoral and cell-related immune reaction. The so-called cell-bound immune reaction is primarily directed against endogenous antigens on cells infected with a virus or an intracellular parasite, tumor cells, chemically modified cells and foreign tissues.
Stanično vezana imuno reakcija se povezuje s tzv. limfocititima (T limfocitima) ovisnim o timusu (stanice koje sazrijevaju u timusu). Na kraju postupka sazrijevanja, dva tipa T limfocita -bazirano na jasno distinktivnim podgrupama njihovih površinskih oznaka (markera) - će biti ispuštena na periferiju. CD4+ stanice, tzv. pomoćne stanice se aktiviraju po pojavi egzogenih antigena i pomažu imuno reakciju povećanjem svoje proizvodnje citokina. CD8+ stanice, tzv. citotoksične stanice se aktiviraju nakon prepoznavanja endogenih antigena, nakon čega razaraju stanice prepoznate kao strane putem citolize. The cell-bound immune reaction is associated with the so-called thymus-dependent lymphocytes (T lymphocytes) (cells that mature in the thymus). At the end of the maturation process, two types of T lymphocytes - based on clearly distinctive subgroups of their surface markers (markers) - will be released to the periphery. CD4+ cells, so called helper cells are activated upon the appearance of exogenous antigens and help the immune reaction by increasing their cytokine production. CD8+ cells, so called cytotoxic cells are activated after recognition of endogenous antigens, after which they destroy cells recognized as foreign through cytolysis.
Približno 2/3 perifernih limfocita su CD4+, a 1/3 CD8+. U skladu s tim, normalni omjer CD4+/CD8+ je 2:1. (Andras Falus; Imunološke stranice 111-138 TEMPUS ITC Bp./1993). Approximately 2/3 of peripheral lymphocytes are CD4+, and 1/3 are CD8+. Accordingly, the normal CD4+/CD8+ ratio is 2:1. (Andras Falus; Immunological pages 111-138 TEMPUS ITC Bp./1993).
Citotoksična imuno reakcija je osnovni zaštitni mehanizam u slučaju intracelularne infekcije zbog toga, što razaranjem inficiranih stanica eliminira mogućnost reprodukcije patogenog agensa. Na sličan način ona ima važnu ulogu u razaranju stanica tumora. U tim slučajevima citotoksična imuno-reakcija služi za zaštitu integriteta organizma. Cytotoxic immune reaction is the basic protective mechanism in the case of intracellular infection because, by destroying infected cells, it eliminates the possibility of reproduction of the pathogenic agent. In a similar way, it plays an important role in the destruction of tumor cells. In these cases, the cytotoxic immune reaction serves to protect the integrity of the organism.
Također su poznati slučajevi u kojima je citotoksična imuno-reakcija nepoželjna ili čak štetna. U slučaju određene autoimunološke zaraze, citotoksična reakcija se usmjerava prema vlastitim stanicama organizma uzrokujući kao rezultat teške funkcionalne poremećaje. Karakteristični primjer imunološkog oboljenja posredovanog T stanicama je reumatoidni artritis. There are also known cases in which the cytotoxic immune reaction is undesirable or even harmful. In the case of a certain autoimmune infection, the cytotoxic reaction is directed towards the body's own cells, causing severe functional disorders as a result. A characteristic example of an immune disease mediated by T cells is rheumatoid arthritis.
Patološka citotoksična reakcija se može vidjeti u slučaju određenih aplastičnih anemija i kroničnog aktivnog hepatitisa. Reakcija odbacivanja koja slijedi nakon transplantacija tkiva ili organa se također zasniva na citotoksičnoj imunološkoj reakciji. U slučaju transplantacije posebnih organa - koštane moždine -tzv. "transplantat protiv domaćina" reakcija ("graft versus host") se također zasniva na citotoksičnoj reakciji. U tim slučajevima omjer CD4+/CD8+ se smanjuje, u određenim slučajevima postaje obrnut, što je uglavnom posljedica povećanja CD8+ stanica, a manje posljedica smanjenja CD4+ stanica. U slučajevima autoimunološke bolesti i reakcijama odbacivanja nakon transplantacija tkiva/organa, uobičajeni postupak liječenja je da se ublažava (smiruje) imunološka reakcija, u određenim slučajevima čak i drastično smanjuje (imunosupresivno liječenje). A pathological cytotoxic reaction can be seen in the case of certain aplastic anemias and chronic active hepatitis. The rejection reaction that follows tissue or organ transplants is also based on a cytotoxic immune reaction. In the case of transplantation of special organs - bone marrow - the so-called "graft versus host" reaction ("graft versus host") is also based on a cytotoxic reaction. In these cases, the CD4+/CD8+ ratio decreases, in certain cases it becomes reversed, which is mainly due to an increase in CD8+ cells, and less due to a decrease in CD4+ cells. In cases of autoimmune disease and rejection reactions after tissue/organ transplants, the usual treatment procedure is to moderate (calm down) the immune reaction, in certain cases even drastically reduce it (immunosuppressive treatment).
Imunosupresivno liječenje uzrokuje ne samo smanjenje broja T limfocita, već ono djeluje i na normalizaciju omjera CD4+/CD8+ stanica. U slučaju alogenog transplantata koštane moždine koji ne sadrži CD8+ stanicu, reakcija "transplantat protiv domaćina" se može zamijetiti u znatno manjem broju. Iz tog razloga, u spomenutim bolestima terapija koja smanjuje posebno broj CD8+ stanica mogla bi biti povoljna. Immunosuppressive treatment causes not only a decrease in the number of T lymphocytes, but also normalizes the ratio of CD4+/CD8+ cells. In the case of an allogeneic bone marrow transplant that does not contain a CD8+ cell, the "graft versus host" reaction can be observed in significantly smaller numbers. For this reason, in the aforementioned diseases, therapy that reduces the number of CD8+ cells in particular could be beneficial.
Na osnovu prije navedenih teoretskih razmatranja i praktičnog iskustva, ispitali smo kakvo djelovanje ima liječenje ipriflavonom na T limfocite odgovorne stanično posredovanu imunološku reakciju te na broj CD4+ pomoćnih i CD8+ citotoksičnih stanica. Za separaciju određenih tipova limfocita i podgrupa koristili smo protočnu citometriju. U kliničkom ispitivanju proučavan je apsolutni broj limfocita i promjena u određenim podpopulacijama limfocita kod 60 pacijenata koji su uzimali dnevnu dozu od 400 mg ipriflavona. Kod 51 pacijenta uočen je blago ili umjereno smanjenje apsolutnog broja limfocita. Srednji apsolutni broj limfocita pacijenata je nakon obrade bio 0.85x109/l (opseg 0.25-0.89). (Normalan opseg: 0.9-3.22x109/l) Kod 9 pacijenata nađen je srednji apsolutni broj limfocita unutar normalnog opsega, 1.84x109/l Kod 51 pacijenta s limfopenijom smanjenje je bilo karakteristično samo za takozvane T limfocite, a među njima primarno i izrazito za CD8+ podpopulaciju. Srednji broj CD8H- je bio 0.08x109l (opseg 0.02-0.23), što predstavlja prilično značajno smanjenje broja stanica uzimajući u obzir normalan opseg od 0.3-1.44x109/l. Based on the previously mentioned theoretical considerations and practical experience, we examined the effect of ipriflavone treatment on T lymphocytes responsible for the cell-mediated immune reaction and on the number of CD4+ helper and CD8+ cytotoxic cells. We used flow cytometry to separate certain types of lymphocytes and subgroups. In a clinical trial, the absolute number of lymphocytes and changes in certain subpopulations of lymphocytes were studied in 60 patients who took a daily dose of 400 mg of ipriflavone. A slight or moderate decrease in the absolute number of lymphocytes was observed in 51 patients. The average absolute number of lymphocytes of the patients after treatment was 0.85x109/l (range 0.25-0.89). (Normal range: 0.9-3.22x109/l) In 9 patients, the mean absolute number of lymphocytes was found within the normal range, 1.84x109/l. In 51 patients with lymphopenia, the decrease was characteristic only for so-called T lymphocytes, and among them primarily and significantly for CD8+ subpopulation. The mean CD8H- count was 0.08x109l (range 0.02-0.23), which represents a fairly significant decrease in cell count considering the normal range of 0.3-1.44x109/l.
Kod 9 pacijenata koji su pokazivali normalan broj limfocita, srednji broj CD8+ je bio 10.43x109/l (opseg 0.28-0.64). Iako je ta vrijednost unutar normalnog opsega, ona pada u njegovu donju četvrtinu, čime se podupire selektivna priroda ovog efekta. Ustanovili smo da se tijekom liječenja ipriflavonom broj T limfocita smanjio na prosjek od 66.6%. Uzimajući u obzir CD4+ pomoćne i CD8+ citotoksične podgrupe, prosječno smanjenje se znatno razlikovalo. Uz 50%-tno smanjenje CD4+ pomoćnih stanica, smanjenje CD8= citotoksičnih stanica je bilo 77%. Omjer CD4+/CD8+ karakterizira različit broj CD4+- i CD8+ stanica, čiji se omjer promijenio na 5:1 nakon liječenja ipriflavonom. In 9 patients who showed a normal lymphocyte count, the mean CD8+ count was 10.43x109/l (range 0.28-0.64). Although this value is within the normal range, it falls in its lower quarter, thus supporting the selective nature of this effect. We found that during treatment with ipriflavone, the number of T lymphocytes decreased to an average of 66.6%. Considering the CD4+ helper and CD8+ cytotoxic subgroups, the average reduction differed significantly. With a 50% reduction in CD4+ helper cells, the reduction in CD8= cytotoxic cells was 77%. The CD4+/CD8+ ratio is characterized by a different number of CD4+ and CD8+ cells, the ratio of which changed to 5:1 after ipriflavone treatment.
Smanjenje broja T limfocita, CD4+ pomoćnih i CD8+ citotoksičnih stanica, kao i temeljna promjena njihovog omjera su značajni iz dva aspekta. Tijekom uobičajenih imunosupresivnih liječenja je uočeno smanjenje broja stanica bilo u pravilu manje od ustanovljenog smanjenja u slučaju ipriflavona. Daljnja značajna razlika je naglašenije smanjenje broja CD8+ citotoksičnih stanica od smanjenja broja CD4+ pomoćnih stanica. Na temelju rezultata može se zaključiti da je ipriflavon sposoban smanjiti ili zaustaviti naročito citotoksičnu reakciju. The decrease in the number of T lymphocytes, CD4+ helper and CD8+ cytotoxic cells, as well as the fundamental change in their ratio, are significant from two aspects. During the usual immunosuppressive treatments, the observed reduction in the number of cells was, as a rule, less than the established reduction in the case of ipriflavone. Another significant difference is a more pronounced decrease in the number of CD8+ cytotoxic cells than the decrease in the number of CD4+ helper cells. Based on the results, it can be concluded that ipriflavone is capable of reducing or stopping a particularly cytotoxic reaction.
Predmet ovog izuma je farmaceutski spoj prikladan za smanjenje broja CD8+ stanica, koji kao aktivni sastojak sadrži 7-izopropoksilizoflavon u smjesi s odgovarajućim inertnim, krutim ili tekućim nositeljem (nosivom komponentom) i po izboru s uobičajenim terapeutskim aditivima i pomoćnim sredstvima (agensima). The subject of this invention is a pharmaceutical compound suitable for reducing the number of CD8+ cells, which as an active ingredient contains 7-isopropoxyisoflavone in a mixture with a suitable inert, solid or liquid carrier (carrier component) and optionally with usual therapeutic additives and auxiliaries (agents).
Gornji spoj se može koristiti za liječenje ljudi ili životinja koji su u stanju u kojem je poželjno selektivno potiskivanje CD8+ limfocita. The above compound can be used to treat humans or animals in a condition in which selective suppression of CD8+ lymphocytes is desired.
Spoj u skladu s predmetnim izumom se može pripremiti u obliku injekcija, infuzije, kapsula, tableta, otopine, sirupa, transdermalnog preparata i dr., prema poznatim postupcima. The compound according to the present invention can be prepared in the form of injections, infusions, capsules, tablets, solutions, syrups, transdermal preparations, etc., according to known procedures.
Bolesti ili stanja u kojima zaustavljanje citotoksične reakcije ima terapeutsku vrijednost su prilično različita po njihovoj prirodi, manifestaciji i tijeku bolesti. Zbog toga se doza mora odrediti prema dijagnozi, početnom broju iimfocita i omjeru Cd4+/CD8+ stanica. Diseases or conditions in which stopping the cytotoxic reaction has therapeutic value are quite different in their nature, manifestation and course of the disease. Therefore, the dose must be determined according to the diagnosis, the initial number of lymphocytes and the ratio of Cd4+/CD8+ cells.
Claims (4)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9502198A HU9502198D0 (en) | 1995-07-21 | 1995-07-21 | Novel indication |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP960345A2 true HRP960345A2 (en) | 1998-02-28 |
Family
ID=10987063
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP9502198A HRP960345A2 (en) | 1995-07-21 | 1996-07-18 | Use of ipriflavone to reduce the number of cd8+ cells |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP0841915A1 (en) |
| JP (1) | JP2001503371A (en) |
| KR (1) | KR19990028933A (en) |
| CN (1) | CN1191483A (en) |
| AR (1) | AR002905A1 (en) |
| AU (1) | AU6367096A (en) |
| BG (1) | BG102182A (en) |
| BR (1) | BR9610187A (en) |
| CA (1) | CA2227421A1 (en) |
| CZ (1) | CZ2798A3 (en) |
| EA (1) | EA199800146A1 (en) |
| EE (1) | EE9800020A (en) |
| HR (1) | HRP960345A2 (en) |
| HU (1) | HU9502198D0 (en) |
| IL (1) | IL122751A0 (en) |
| MX (1) | MX9800603A (en) |
| NO (1) | NO980127D0 (en) |
| PL (1) | PL324460A1 (en) |
| SK (1) | SK3298A3 (en) |
| WO (1) | WO1997003664A1 (en) |
| YU (1) | YU42796A (en) |
| ZA (1) | ZA966079B (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1241079B (en) * | 1990-03-23 | 1993-12-29 | Chiesi Farma Spa | PHARMACEUTICAL COMPOSITIONS CONTAINING IPRIFLAVONE, PROCEDURE FOR THEIR PREPARATION AND RELATED THERAPEUTIC USE |
| HU212932B (en) * | 1993-08-02 | 1996-12-30 | Chinoin Gyogyszer Es Vegyeszet | Parmaceutical composition containing ipriflavone, hydroxyapatit and tricalciumphosphate for treating lack of bones and process for producing the composition |
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1995
- 1995-07-21 HU HU9502198A patent/HU9502198D0/en unknown
-
1996
- 1996-07-16 EA EA199800146A patent/EA199800146A1/en unknown
- 1996-07-16 CN CN96195722A patent/CN1191483A/en active Pending
- 1996-07-16 IL IL12275196A patent/IL122751A0/en unknown
- 1996-07-16 CZ CZ9827A patent/CZ2798A3/en unknown
- 1996-07-16 KR KR1019980700235A patent/KR19990028933A/en not_active Application Discontinuation
- 1996-07-16 CA CA002227421A patent/CA2227421A1/en not_active Abandoned
- 1996-07-16 MX MX9800603A patent/MX9800603A/en unknown
- 1996-07-16 JP JP50646497A patent/JP2001503371A/en active Pending
- 1996-07-16 PL PL96324460A patent/PL324460A1/en unknown
- 1996-07-16 EE EE9800020A patent/EE9800020A/en unknown
- 1996-07-16 AU AU63670/96A patent/AU6367096A/en not_active Abandoned
- 1996-07-16 BR BR9610187A patent/BR9610187A/en not_active Application Discontinuation
- 1996-07-16 EP EP96923004A patent/EP0841915A1/en not_active Withdrawn
- 1996-07-16 WO PCT/HU1996/000038 patent/WO1997003664A1/en not_active Application Discontinuation
- 1996-07-16 SK SK32-98A patent/SK3298A3/en unknown
- 1996-07-17 ZA ZA9606079A patent/ZA966079B/en unknown
- 1996-07-18 HR HRP9502198A patent/HRP960345A2/en not_active Application Discontinuation
- 1996-07-19 YU YU42796A patent/YU42796A/en unknown
- 1996-07-22 AR ARP960103677A patent/AR002905A1/en unknown
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1998
- 1998-01-12 NO NO980127A patent/NO980127D0/en unknown
- 1998-01-14 BG BG102182A patent/BG102182A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AR002905A1 (en) | 1998-04-29 |
| EE9800020A (en) | 1998-08-17 |
| SK3298A3 (en) | 1998-07-08 |
| KR19990028933A (en) | 1999-04-15 |
| AU6367096A (en) | 1997-02-18 |
| EP0841915A1 (en) | 1998-05-20 |
| CZ2798A3 (en) | 1998-06-17 |
| CA2227421A1 (en) | 1997-02-06 |
| MX9800603A (en) | 1998-04-30 |
| BG102182A (en) | 1998-08-31 |
| IL122751A0 (en) | 1998-08-16 |
| NO980127L (en) | 1998-01-12 |
| JP2001503371A (en) | 2001-03-13 |
| HU9502198D0 (en) | 1995-09-28 |
| PL324460A1 (en) | 1998-05-25 |
| ZA966079B (en) | 1998-01-19 |
| EA199800146A1 (en) | 1998-08-27 |
| BR9610187A (en) | 1998-07-28 |
| YU42796A (en) | 1999-03-04 |
| WO1997003664A1 (en) | 1997-02-06 |
| NO980127D0 (en) | 1998-01-12 |
| CN1191483A (en) | 1998-08-26 |
| WO1997003664A8 (en) | 1999-08-05 |
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