HU212114B - Cotton wool, mull, vagina medical baren and surgical bandage having antimicrobe effect based cellulose - Google Patents

Abstract

FIELD OF THE INVENTION The present invention relates to a crystal violet composition of 0.005 to 10% by weight, including a vaginal base made of the above cotton wool, a cellulosic tampon without auxiliary material, a surgical tupfer, a surgical and fast-wound base wool and a 0.005 to 0.05% w / w crystalline wool. and a pulp-based cellulose-based bubble tissue of the above bladder tissue. The binding material. B Scope of the description: 4 pages

Description

FIELD OF THE INVENTION The present invention relates to microbastatic and microbicidal cellulose wadding for use in the manufacture of sustained release tampons, tufts, first aid bandages and surgical compresses for the prophylaxis and treatment of certain bacterial and fungal infections. The present invention also relates to wound dressings, medicated tampons and wound dressings which have the same biological effect and which can be used for dressings.

Prevention, reduction and treatment of pathogenic infections are important tasks for both surgery and gynecology. The efficacy of the topical treatment can be increased by the use of a polymer containing the active ingredient: e.g. The advantage of drug-containing tampons, as opposed to other vaginal drugs (suppositories, balls, tablets, ointments, rinses, aerosols), is that it prevents leakage of the drug, so that it can be used not only when lying down, which allows even and night-time administration.

Small molecule polymers containing biologically active substances are well suited for applications where biological activity is required for a prolonged period of time and the desired processes take place on the surface of the polymer. The macromolecular system containing the right amount of active ingredient, as a warehouse, ensures a continuous supply.

It is crucial that the polymer releases the active ingredient at a rate appropriate to the biological process. The rate of separation is determined by the wettability of the polymer (a) and the rate of hydrolysis of the polymer-drug bond (b).

(a) The release and transport of the bioactive substance requires moisture: under the same conditions, the hydrophilic polymer has a higher biological activity than the hydrophobic.

(b) The more difficult it is to hydrolyze the polymer-drug bond, the lower the biological activity of the associated system, as demonstrated for bactericidal metal ions and organic compounds. If hydrolysis is slow or completely inhibited, the biological effect is not sufficient. In the case of too rapid hydrolysis, the polymer immediately loses its activity: the active ingredient is washed away and partially leaves the surface to be treated, i.e., the situation becomes similar to a topical treatment without active polymer (eg, brushing) (Anonym: Nonwovens industry 72: 22).

Of the possible bonds between the polymer and the active compound, ionic, coordination and easily hydrolyzing covalent bonds have been found to be the most suitable.

The use of ionic agents in wound dressing and tamponization is widespread on cotton cellulose as a carrier, since the cotton contains no cationic groups at all and small amounts of anionic groups (carboxyl). This problem was solved by chemically modifying cellulose and introducing cationic or anionic groups (European Patent No. 338,173). Others (European Patent No. 272,149) have used a complex polymer-based carrier having a high carboxyl content, which contains a highly swellable cellulose derivative in body fluids.

The bactericidal activity and therapeutic use of the triphenylmethane cationic dye has long been known. Major representatives are brilliant green, malachite green, gentian violet, crystal violet, of which the latter two in particular (A, Végh, A., Szász, Gy., Takács, M .: Pharmaceutical Chemistry, Medicina, Budapest, 608 (19877)) have a strong microbicidal action. and vaginal bacteria and fungi, but while the first three cause an unpleasant side effect (contact with body tissues at high concentrations), crystal violet is already bactericidal at very low concentrations and has no side effect [von Spitzbart, H., Mende, Η . E.: Zb. Gynakol. 104, 584 (1982)]. It is used in medicine under the name Genticid in the form of a 1% solution and 2% talcum powder.

It follows from the above that bactericidal cationic dyes may be suitable for the production of biologically active fibrous materials (tampons, bandages) since their cations are capable of forming ionic bonds which are degraded by bodily fluids when attached to a carrier containing anionic groups. The active ingredient is released from the polymeric carrier according to the rate of degradation and thus has the ability to exert its microbastatic and microbicidal activity over time.

Cotton cellulose, which is primarily used in the manufacture of bandages and tampons, is not suitable for this purpose, according to the basic knowledge of textile dyeing, because the cationic (basic) dyes have a very low affinity for cellulose. stains in combination with tannin in combination with antimony salts or sulfur-containing phenols. Of course, the use of the aforementioned excipients on a bandage or tampon is out of the question.

Depending on the viscose or cotton bleaching technology, the viscose fiber made from regenerated cellulose is approx. It contains 3 to 10 times more carboxyl groups than cotton and is therefore expected to bind more cationic agents. This was utilized to produce microbicidal viscose tissue: 0.5% brilliant green was applied to the fiber to achieve proper activity. The microbicidal fabric thus obtained was intended to be used for purposes in which it is necessary to wash the linen (for example, bed linen) and, since the microbicidal effect was found to be non-washable, this process was not discussed later.

For the preparation of a polyurethane foam based microbicidal vaginal swab [No. 3,902,493]. U.S. Pat. H. Triponylmethane-type dyes, namely at least 0.1% by weight of gentian violet, which is pentamethylpararosanilium chloride and hexamethyl- a mixture of pararozanilinium chloride (crystal violet). Multi-layer dressings containing various active ingredients including anti-inflammatory dyes and water in a tank-like system have been prepared (U.S. Patent No. 4,204,214 and WO 8,911,850) to a wound dressing (gauze, foam, tampon).

HU 212 114 B

SUMMARY OF THE INVENTION It is an object of the present invention to provide a cotton-based dressing and tampon that is reasonably widespread in wound dressing and tampon because of its ability to absorb and transport moisture, with low and low cost and effective against wound and vaginal infections.

The present invention is based on the following findings:

1. Bleached cotton cellulose contains as many carboxyl groups as is required to ionically bind an effective amount of crystal violet. Anionic modification of cellulose is unnecessary when using this drug.

2. While the crystal violet in solution or sachet powder should be used at a concentration of 1-2%, in vitro studies have shown that crystal violet on cotton wool kills Streptococcus faecalis bacteria at a concentration of 500 pg dye / g fiber within 2 hours. 1/3 of the Escheria coli bacterium. 20%, after 6 hours contact time, 2/3 of the same bacteria, or ca. 35%.

3. Fewer active ingredients against Candida albicans fungus: 50 pg of dye per gram of fiber per 2 hours destroys fungi by approx. half in about 6 hours. 80% of the total. At a concentration of 500 pg dye / g fiber, the fungi should have a concentration of ca. 90% of them die, while a contact time of 6 hours was sufficient for complete destruction.

4. Lactobacillus plantarum, an acidic bacterial bacterium of the vagina's natural flora, is less susceptible to crystal violet (the C / L pairs represent the Lactobacillus death rate for Candida albicans listed above / L = 50): 30; 80/40; 90/40; 100/75. Thus, once the vaginal fungal infection has ceased, it is possible to restore the natural microflora of the vagina.

5. Although the textile dyeing experience shows that the basic dyes have very poor washing resistance without the use of staining, the crystal violet does not come off the cotton pulp during high pressure steam sterilization and does not color the paper used for packaging.

6. The fiber gradually releases the active ingredient, thus its microbastatic or microbicidal effect is prolonged. Under in vitro conditions, at 37 ° C, one gram of cotton cellulose modeled with 1 g of liquid on the surface of the fiber in the case of abundant vaginal and wound exudation, after 2 hours 12% of the active substance and 55% of the active substance away the thread. The maximum application time is 6 hours for vaginal swabs and 24 hours for bandages. during this time, 13% of the crystal violet is desorbed in artificial vaginal secretion, and 60% in serum, so the cotton cellulose carrier provides the active ingredient throughout its contact time.

7. In serum, drug release is much faster than vaginal secretion: under the conditions described in point 6, 4591 of the crystal violet is deposited within 5 minutes. In shorter desorption times, the reproducibility of the measurement is poor, but without specific data it can be stated that the active compound cotton wool can also be used with very short contact times (surgical tupfer).

8. Cotton wool with microbastatic and microbicidal effects has no harmful side effects.

(a) Cotton swabs containing 500 pg / g of dye will not cause skin irritation when applied to healthy and scarified skin of New Zealand rabbits for 14 days for 4 hours per day.

(b) In Wistar rats, there was no difference in the effect of drug-free and crystal violet wadding on sterile wounds for 14 days.

(c) Under sterile conditions, the effect of cotton wool sewn on Wistar rats is not affected by crystal violet.

(d) A cotton swab containing 500 pg / g dye in New Zealand rabbit pods for 7 days and Wistar rats for 6 days did not cause adverse lesions on macroscopic and histopathological examination.

Accordingly, the present invention relates to a cellulose-based wadding containing 0.005 to 10% by weight of crystal violet and to a cellulose-based wadding containing 0.005 to 0.06% by weight of crystal violet. The preferred use of the wadding according to the invention is a vaginal swab, surgical tupper, surgical and quick dressing compress, and the woven tissue according to the invention can be used as a wound dressing.

The manner in which microbastatic and microbicidal wadding and woolen fabrics are produced, without limiting the scope of the invention, is illustrated by the following examples:

/. example

After bleaching, 1 kg of cotton wool is treated with 6 l of an aqueous crystal violet solution having a dye concentration of 0.006% w / w. The temperature of the bath was raised to 60-70 ° C, held at that temperature for 1 hour, and then cooled and lowered to room temperature. This cotton wool is centrifuged without rinsing to 60% moisture and then dried at 110-120 ° C to 12-15% moisture. The cotton wool thus produced is used to make a tampon, which is suitable for the treatment of minor vaginal infections caused by the fungus Candida albicans.

Example 2

In each example, the dye concentration was 0.06% by weight. This cotton swab can be used to make compresses that are more severe or bacterial vaginal infections, as well as surgical tampons, surgical tupers, surgical and quick dressings.

Example 3

All of the procedures described in Example 2 were followed, except that woolen woven fabrics made from cotton or viscose instead of cotton wool or mixed with other fibers were used. The mulled fabric thus made can be prepared in a variety of shapes.

Example 4

In each case, the same procedure as in the first example was used, except that the dye concentration should be 10% by weight of the cotton wool. The cotton wool so produced was produced in a ratio of 1: 150 by weight

Dilute with cotton dye obtained after bleaching but not dyed. The cotton wool so produced is used to form a therapeutic swab, surgical tuft, or bandage.

Thus, the advantages of the microbastatic and microbicidal cotton wool and mull fabrics of the present invention can be summarized as follows:

1. The microbastatic or microbicidal dressing (gauze or cotton wool compress) can be used effectively against pathogenic microorganisms both in surgeries and as an instant dressing, as a microbastatic or microbicidal cotton swab and as a vaginal swab. The bactericidal and fungicidal action is short (especially for blood, wound exudate) and long duration of contact.

2. The crystalline violet applied to bleached cotton cellulose is effective against microorganisms that cause gingival or vaginal inflammation at a concentration (0.005-0.06% by weight) of crystalline violet applied in solution or sachet powder or gentian violet applied to polyurethane tampon as carrier. This concentration of active ingredient can also be considered low compared to the application concentration of other active substances used for microbastatic or microbicidal dressings and tampons.

3. Microbastatic and microbicidal tampon significantly less kills lactic acid bacteria belonging to the natural microflora of the vagina than fungi of Candida albicans, so that after the disappearance of the fungal infection it is possible to regenerate the vaginal flora naturally.

4. The production technology is simple, the active ingredient does not come off the fiber during high pressure steam sterilization.

Claims (4)

PATENT CLAIMS Cellulose-based wadding, characterized in that: It contains from 0.005 to 10% by weight of crystal violet. A vaginal tampon, surgical tupper, surgical and dressing compress, characterized in that it is manufactured from cotton wool according to claim 1 in a known manner. Cellulose-based bubble tissue, characterized in that it contains 0.005-0.06% by weight of crystal violet. 4. A wound dressing, characterized in that it is made of a woven fabric according to claim 3 in a known manner.