EP0248046A1 - Medicament for use against circulatory disorders - Google Patents
Medicament for use against circulatory disordersInfo
- Publication number
- EP0248046A1 EP0248046A1 EP86906828A EP86906828A EP0248046A1 EP 0248046 A1 EP0248046 A1 EP 0248046A1 EP 86906828 A EP86906828 A EP 86906828A EP 86906828 A EP86906828 A EP 86906828A EP 0248046 A1 EP0248046 A1 EP 0248046A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- medicament according
- circulatory disorders
- medicament
- potassium
- concentration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
Definitions
- the invention relates to a medicament for combating circulatory disorders.
- Circulatory disorders are caused by various causes. You can, for example, purely mechanically by z. B. thrombus or embolus or by a vascular stenosis in changes in the vascular wall or by cardiovascular-related drop in blood pressure below a critical lower perfusion pressure. Furthermore, disorders of the blood composition can lead to circulatory disorders. The blood circulation in an organ or in the whole organism can only be reduced or completely abolished compared to the normal state. As a result of the circulatory disorder, there is a lack of oxygen and a lack of substrate, a reduced removal of the metabolic end products and damage to the cell membranes in the affected organ or in the entire organism.
- the K concentration can rise up to a maximum of 100 mmol per liter and lead to a complete occlusion of the arterial blood vessels.
- An increase in the extracellular K concentration, which has a narrowing effect on the vessels, can also take place by releasing potassium ions from erythrocytes after bleeding into the tissue, for example after subarachnoid hemorrhage in the case of aneurysms of the brain arteries.
- Cerebral and coronary circulatory disorders are common in the population. There is therefore a need to provide a drug for the treatment of these diseases.
- the aim of the invention was therefore to provide a medicament which is suitable for the treatment of circulatory disorders, in particular in the cerebral and coronary area.
- a medicament for combating circulatory disorders which is characterized in that it contains at least one substance which intercepts potassium ions at physiological pH values, optionally together with conventional physiological additives, solvents and / or diluents contains.
- the medicament contains a substance that intercepts potassium ions.
- This active ingredient exhibits the K-ion trapping properties at both normal and pathophysiological pH values.
- a compound is used which can selectively complex potassium ions, whereby Na, Ca and Mg are not complexed.
- the compound should preferably be water-soluble since it is supplied to the blood. It should also not be too fat-soluble so that it cannot penetrate the cell membrane. Of course, this substance must not be toxic to humans. Furthermore, it must not be mutagenic or teratogenic.
- the substance trapping potassium ions is preferably used together with conventional physiological additives, solvents and / or diluents. These means are known to the person skilled in the art.
- R_. , R 2 and R ⁇ independently of one another denote an alkyl group with 1 to 4 C atoms and n, p and q independently denote an integer from 1 to 5.
- cryptates are excellently suitable for the selective complexation of potassium ions. They are water soluble and non-toxic. Compounds in which R 1 , R 2 and R 3 represent a C 2 alkyl group and n, p and q 2 are particularly preferably used.
- Another preferred substance trapping potassium ions is a crown ether.
- C atoms 1,2 and 7,8 can be part of a cyclohexyl or benzyl group.
- crown ethers are also very well suited for selectively complexing potassium ions. Crown ethers in which the two rings are substituted with hydrophilic groups are preferably used.
- Customary additives can also be added to the drug.
- physiologically suitable buffer substances come into consideration. Tris buffer, bicarbonate or phosphate buffer are used in particular as buffer substances.
- the drug is still a thrombolytic additive is added. This is particularly useful if the circulatory disorder to be treated due to a vascular blockage z. B. was triggered by a thrombus in an infarction.
- Anti-dehydrating agents can also be added to the drug.
- the medicament according to the invention is suitable for treating all types of circulatory disorders. It can be used to treat circulatory disorders in all organs and in the whole organism.
- the agent is suitable for generalized and local circulatory disorders. It is particularly preferably used in the treatment of cerebral and coronary circulatory disorders. A preferred application is also the treatment of cerebral circulatory disorders in the newborn infant.
- the agent can be applied systemically. Due to its good water solubility, the agent can be administered in the form of injections and infusions. The injection is preferably carried out intra-arterially. However, it is also possible to administer the agent intravenously. As an infusion, the drug is preferably contained in a rheologically effective infusion for hemodilution of the blood. In addition, the agent can also be administered orally in the form of drops or tablets. In a further preferred embodiment, the agent is used to treat circulatory disorders in individual organs injected directly into the affected organ. For example, in the case of a cerebral infarction, the agent is injected directly into a cerebral artery, and in the case of a heart attack, the agent is injected directly into the heart. In particular if the heart is affected, it is also preferred to place a catheter and to introduce the agent through this catheter.
- the agent can also be applied locally from the outside to the affected organ. So z. B. after bleeding in the area of the pial brain arteries, the agent is applied to the brain through a borehole or during the neurosurgical operation in order to eliminate the localized or generalized spasms due to the K release after bleeding.
- the dose of the drug depends on the type and location of the circulatory disorder.
- the agent can be dosed precisely depending on the potassium concentration at the site of the circulatory disorder.
- the drug is preferably used in a concentration such that the potassium ion concentration is set in a range from 3 to 20 mmol, particularly preferably 3 to 10 mmol.
- Circulatory disorders and vascular occlusions can be treated with the medicament according to the invention.
- the remedy the vascular constriction is removed and the ischemia is eliminated.
- Example 1 The invention will be illustrated by examples: Example 1
- K + activity of the cerebral cortex was measured with a K + sensitive valinomycin surface electrode on an anesthetized rat. The physiological parameters were in the normal range.
- the K starting concentration on the brain cortex was 4.5 mmol / l and was constant.
- About 100 ⁇ l of a 100 mmol KC1 solution were then dripped onto the entire exposed surface of the brain.
- the K activity of the brain rose to 34 mmol / 1. Drop of 100 mmol (2.2.2) -
- K value only increase to 5.6 mmol / 1.
- a further addition of cryptate led to a decrease in the K + activity in the tissue to 4.4 mmol / l.
- the K electrode was removed from the tissue and rinsed the surface of the brain several times with warm physiological NaCl L ⁇ sung and NaCl "aspirated. Then, the K electrode was set up again and a K value of 4.5 mmol / 1 was measured. Renewed application of 100 mmol KCl solution now led to an increase in K in the tissue to 20 mmol / l. By adding (2,2,2) cryptate, the K concentration dropped to 4.5 mmol / l within 2 1 /2 minutes.
- the blood flow was registered continuously over approximately 10 minutes with normal physiological control parameters and a normal K value in the brain and steady state conditions. During this time the blood flow remained completely constant and was in the normal range. Then 30 ⁇ l of a 100 mmol KC1 solution was applied to the brain surface directly at the measuring point. The blood flow showed a two-phase course. At first it rose immediately and decreased again after about 10 seconds and fell well below the initial value. There was insufficient blood flow (ischemia). After a further 40 seconds, approximately 40 ⁇ l (2,2,2) cryptate was added to the brain tissue from the outside. The blood flow increased rapidly within a few seconds and was above the starting area after about 1 minute. " - Example 3
- the effect of (2,2,2) cryptate on the K concentration was tested in an unbuffered and buffered solution.
- the K + concentration in the solution was measured using a K-sensitive valinomycin.
- the K ions were present as dissolved KCl in physiological (0.9%) NaCl.
- physiological (0.9%) NaCl The pH of the solution was adjusted with concentrated NaOH.
- the solutions (both the KCl starting solution and the cryptate solution were buffered to pH 7.0 with 0.1 M phosphate buffer (Na-HPO. + NaH-PO.).
- the following mixtures were used as the starting solution: 4 ml of 50 mM KCl; 0.9% NaCl; 0.1 phosphate buffer pH 7.0 1 ml 250 mM (2.2.2) cryptate; 50 M KCl; 0.9% NaCl; 0.1 M phosphate buffer.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Footwear And Its Accessory, Manufacturing Method And Apparatuses (AREA)
Abstract
Le médicament ci-décrit contient comme substance active au moins une substance captant des ions de potassium à des valeurs pH physiologiques, comme par ex. un composé de formule générale (I) dans laquelle R1, R2 et R3 représentent chacun un groupe alkyle comprenant de 1 à 4 atomes de carbone, et n, p et q représentent indépendamment les uns des autres un nombre entier de 1 à 5, ou un éther en couronne, éventuellement avec des additifs, solvants et/ou diluants physiologiques usuels.The described medicament contains as active substance at least one substance which scavenges potassium ions at physiological pH values, such as e.g. a compound of general formula (I) in which R1, R2 and R3 each represent an alkyl group comprising from 1 to 4 carbon atoms, and n, p and q independently of each other represent an integer from 1 to 5, or a crown ether, optionally with customary physiological additives, solvents and / or diluents.
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE3543974 | 1985-12-12 | ||
DE19853543974 DE3543974A1 (en) | 1985-12-12 | 1985-12-12 | MEDICINAL PRODUCTS TO REDUCE CIRCULATION |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0248046A1 true EP0248046A1 (en) | 1987-12-09 |
Family
ID=6288296
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP86906828A Withdrawn EP0248046A1 (en) | 1985-12-12 | 1986-12-02 | Medicament for use against circulatory disorders |
Country Status (5)
Country | Link |
---|---|
US (1) | US5008269A (en) |
EP (1) | EP0248046A1 (en) |
JP (1) | JPH01500175A (en) |
DE (1) | DE3543974A1 (en) |
WO (1) | WO1987003479A2 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4116889A1 (en) * | 1991-05-23 | 1992-11-26 | Leniger Follert Elfriede Prof | MEDICINAL PRODUCTS TO REDUCE CIRCULATION |
-
1985
- 1985-12-12 DE DE19853543974 patent/DE3543974A1/en not_active Withdrawn
-
1986
- 1986-12-02 EP EP86906828A patent/EP0248046A1/en not_active Withdrawn
- 1986-12-02 WO PCT/EP1986/000695 patent/WO1987003479A2/en not_active Application Discontinuation
-
1987
- 1987-11-11 JP JP62507080A patent/JPH01500175A/en active Granted
-
1989
- 1989-04-24 US US07/342,756 patent/US5008269A/en not_active Expired - Lifetime
Non-Patent Citations (1)
Title |
---|
See references of WO8703479A2 * |
Also Published As
Publication number | Publication date |
---|---|
WO1987003479A2 (en) | 1987-06-18 |
US5008269A (en) | 1991-04-16 |
JPH01500175A (en) | 1989-01-26 |
WO1987003479A3 (en) | 1988-07-28 |
JPH0223162B2 (en) | 1990-05-23 |
DE3543974A1 (en) | 1987-06-19 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19870812 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: LENIGER-FOLLERT, ELFRIEDE |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: LENIGER-FOLLERT, ELFRIEDE |
|
D17D | Deferred search report published (deleted) | ||
17Q | First examination report despatched |
Effective date: 19900330 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 19901010 |