DE102006006905A1 - Hemostatic agent - Google Patents

Abstract

Minerals of volcanic origin that occur in nature can, after appropriate processing, be used as fine natural zeolite granules for hemostasis and / or for wound healing and / or in cosmetic or medical formulations and are superior to conventional commercial preparations.

Description

The This invention relates to the use of naturally occurring zeolites as an agent for hemostasis and / or for the production of cosmetic or medical formulations.

was standing of the technique

• a) Proteindenaturierung z.B. durch Metallsalze
• b) mikroporöse Biopolymere bzw. Biopolymere mit großer innerer Oberfläche. Diese absorbieren Wasser, dadurch kommt es zu einer Konzentration der roten Blutzellen sowie der Gerinnungsfaktoren. Als besonders vorteilhaft haben sich Polysacharide erwiesen, die aus poly-N-acetyl-glucosaminen oder Chitosan bestehen. Diese sind z.B. im Skelett von Insekten, aber auch in Algen enthalten. Biopolymere wie Gelatine, Fibrinschwämme oder oxidierte Cellulose haben eine große innere Oberfläche. Abgrund der Absorption an diese große Fläche kommt es zu einer Konzentration der Gerinnungsfaktoren.
• c) Enzyme, insbesondere durch Thrombin oder proteolytische Enzyme mit thrombinähnlicher Wirkung mit oder ohne Zusatz von Calcium
• d) hochkonzentrierte Gerinnungsfaktoren
• e) Kombinationen von c) und d)
• f) Calcium-Alginate
• g) alumosilikatische Syntheseprodukte mit Mikroporenstruktur

Hemostasis can be achieved by the prior art

• a) protein denaturation, for example by metal salts
• b) microporous biopolymers or biopolymers with a large internal surface. These absorb water, resulting in a concentration of red blood cells and coagulation factors. Polysacharides which consist of poly-N-acetyl-glucosamines or chitosan have proved to be particularly advantageous. These are included, for example, in the skeleton of insects, but also in algae. Biopolymers such as gelatin, fibrin sponges or oxidized cellulose have a large internal surface area. Abyss of absorption to this large area, it comes to a concentration of coagulation factors.
• c) enzymes, in particular by thrombin or proteolytic enzymes with thrombin-like action with or without the addition of calcium
• d) highly concentrated coagulation factors
• e) combinations of c) and d)
• f) calcium alginates
• g) aluminosilicate synthesis products with microporous structure

For the present Invention provide the aluminosilicate synthesis products with microporous structure Closer prior art.

The previously used for hemostasis synthesis products are alkaline and alkaline earth aluminum silicates of different composition

On the basis of synthesized and completely dehydrated at over 400 ° C Erdalkalialuminiumsilicaten was purchased from Z-Medica, U.S. for the immediate treatment of War wounds and emergency supplies a synthesis product. A strong exothermic reaction removes water from the blood and it comes to hemostasis. The synthesis product becomes direct applied in granular form to the wound. It is sold under the name "Quikclot". adversely was described in this product that by the exothermic Reaction (temperatures up to 60 ° C) damage of the adjacent tissue occur. (Journal of Trauma 54 (2003) 6, 1077-1082).

Synthetic lithium aluminosilicates ( EP 1176991 A1 WO 00/69480) have been developed specifically for wound care and are sold under the trade name CERDAC. In the case of CERDAC, using high temperatures (> 1000 ° C), a microporous ceramic product is produced in order to achieve optimal wound care. Apart from the sometimes complex production, the capillary force effect is too low to meet all requirements.

task The invention was the disadvantages mentioned in the prior art eliminate and new opportunities for one To provide hemostasis.

The Task became according to the characteristics of the claims by natural zeolite granules, obtainable from natural Minerals with a zeolite content of> 70%, dissolved. According to the invention were means provided on the basis of natural substances that are used for rapid hemostasis in case of injuries, for hemostasis in planned operations as well can be used for wound care.

According to a preferred embodiment of the invention, natural minerals with a content of> 70% zeolite, preferably with fractions of clinoptilolite, chabazite and mordenite, are fractionated after drying and pre-comminution. The fraction is used with grain size 0.8-0.2 mm. Regarding purity, the requirements are US Pharmacop. or Europ. Pharmacorp. to fulfill. The gentle dehydration takes place at temperatures below 200 ° C by treatment at selected temperature intervals. According to the invention, a fine mineral granules are obtained with strong electrostatic fields in the crystal lattice, which can stop even heavy bleeding within 1 min. Surprisingly, it has been found that the product according to the invention is based on products based on microporous synthetic lithium silicates ( EP 1176991 A1 , WO 00/69480, US 6833486 B1 ) z. B. CERDAC is superior by a 5-10 times higher capillary force effect. As a result of the partial dehydration no exothermic reaction occurs, which can cause tissue damage by burning.

The allows the application for hemostasis, because coagulation factors due to the high capillary force can be effectively concentrated.

The high capillary power is also for the use for wound care, especially for the care of difficult healing and already chronic wounds of particular importance. Particularly indicated is the use in wounds with an exudation, i.e. leakage of blood components to an inflamed wound. Often, exudation is an indication of infection from an injury The invention obtained Microporous structure allows the uptake of wound exudate that is released in excess in the case of "weeping" wounds ensures the absorption of excess exudate for one humid atmosphere over the Wound, what for Wound healing, especially for the prevention of dermatological Late damage, from Meaning is. The agent is particularly suitable for use in high-risk patients such as diabetics and dialysis patients.

Completely surprising it was found that the zeolites prepared according to the invention also keep their hemostatic properties in moist mixtures. Thereby the application is also possible in moist wound treatment.

By this surprising Result will be about it completely out opened up new fields of application, e.g. the combination of zeolite granules with mineral cleaning agents in the production of toothpastes as well as other applications in cosmetic and medical formulations.

The Naturzeolithfeingranulate can in an envelope - preferably cellulose or textile based or collagen fleece - where advantageously a fixation in the desired Position can be done by quilting and sewing.

Selected natural zeolites can prepared according to the invention They are now on cost-effective direct route as hemostatic Means and means for wound care can be provided.

The Invention is based on embodiments explained without being limited to these examples.

EXAMPLE 1:

manufacturing the natural zeolite fine granules

Selectively mined minerals ≥ 70 % Of zeolite, preferably clinoptilolite, chabazite and mordenite are after drying and pre-crushing by fractionation won with grain band 0.8-0.2 mm. Regarding purity are the requirements to US Pharmacop or Europ. Pharmacorp. to fulfill. By gentle thermal Treatment in selected Temperature intervals at temperatures <200 ° C is a partial dehydration preserving the crystal lattice structure.

EXAMPLE 2

Examination of the micropore volume, grain distribution and capillary force action

The products prepared according to Example 1 have 25-50% micropore space (in terms of total volume) and average nanopore diameter in the range 0.3-0.5 nm.

Nanopore size and fine granules construction enable a maximum blood adsorption and rapid penetration of the adsorber granules.

The Capillary force effect is 5 to 10 times higher than the comparative one examined commercial preparation Cerdac.

EXAMPLE 3

Testing the fine granules Suitability for hemostasis

Methodology:

It 2 fine granules, prepared according to Example 1, were tested.

The Investigations were carried out on the rat liver as a prototype for a strong perfused organ. Rats were anesthetized for this purpose. After opening of the abdominal cavity was about 1 cm long with the scalpel made. The bleeding was filmed. The time to haemostasis was measured.

Result:

at Application of the granules according to the invention a hemostasis is achieved within 1 min (control until to 8 minutes). It forms a scab-like encrustation that the Wound protects.

EXAMPLE 4

Examination of Natural zeolite fine granules in a wrap of collagen fleece Suitability for hemostasis

The Naturstofffeingranulat was in the liver section model according to example 3 tested. In use, the granules were in contrast to Example 3 not sprinkled but in a nonwoven made of native resorbable Collagen fibers, made of pig skin, wrapped.

Result:

It becomes a no longer bleeding, superficially closed wound visually good wound closure. The blood loss will be immediate reduced. The soft sponge-like fleece can be advantageous with the Naturstofffeingranulaten be combined.

EXAMPLE 5

In vitro testing of Fine granules suitable for hemostasis

b) Mangelplasma

c) Heparinplasma (mit 2 und 3 min Vorinkubation)

In the case of investigations on different blood plasmas the following results were obtained: a) normal plasma (with preincubation of 2 min)

b) Deficient plasma

c) Heparin plasma (with 2 and 3 min preincubation)

The Results show that the endogenous coagulation system is activated with the deficiency factor F - VII and tissue factor to reinforced Lead to trombinin and fibrin formation. There is a relative fibrin concentration increase by the mineral Wound dressing according to Example 1.

Example 6: Toothpaste formulation

Result:

The Stability and load tests all requirements after 12 months of testing and monitoring.

Claims (10)

An agent for hemostasis, characterized in that they contain as active component Naturzeolithfeingranulate available from natural minerals with a zeolite content of ≥ 70%. Means according to claim 1, characterized in that it is the zeolite-containing minerals clinoptilolite and / or Chabazite and / or mordenite. Agent according to claim 1 or 2, characterized that the minerals by grinding and fractionation as well as gentler Partial dehydration be pretreated at temperatures <200 ° C. Agent according to one of claims 1 to 3, characterized that the natural zeolite fine granules in an envelope, preferably based on cellulose or on a textile basis or a collagen fleece. Use of natural zeolite fine granules, obtainable from natural Minerals with a zeolite content of> 70%, for hemostasis or for production of cosmetic and / or medical formulations. Use according to claim 4 or 5, characterized that it is the zeolite-containing minerals clinoptilolite and / or Chabazite and / or mordenite. Use according to claim 4 or 5, characterized that the minerals by grinding and fractionation as well as gentler Partial dehydration be pretreated at temperatures <200 ° C. Use according to one of claims 5 to 7 as a means for First aid after accidents. Use according to any one of claims 5 to 8 for wound treatment. Use according to one of claims 5 to 7 for the preparation of toothpastes.