DE1930876A1 - Threads and other materials with long-lasting germicidal properties - Google Patents

Description

The PA ^T fcNTANv ». 'Atf.DiPL.-J.NG..W. Beyer 6000 Frankfurt / main Dipl.-Wirtsch.-Ing. B. Jochem Freiherr-vom-Stein-Strasseis

InSidient Ar.i | 9 J [) Q / Q

Sutures Inc.

Coventry, Connecticut / USA

Threads and other materials with long-lasting germicidal properties.

Priority of the US application Ser. No. 737 340 of June 17, 1968 «

From fibrous proteins or other nitrogen-containing amphoteric film-forming organic substances such as polymers materials made in the form of fibers, threads, films, yarns, fabrics and finished textile products with long Persistent germicidal properties are due to chemical combination of germicidal ions with the nitrogenous ones amphoteric substrate or the base material. The germicidal ions can essentially do not remove from the base material by solvent extraction. That proves that the ions chemically get to the base material are bound. For example, threads like silk thread can be made germicidal for long periods of time by a silk thread with an aqueous solution of a cationic or anionic germicidal surface active By means of e.g. a germicidal quaternary ammonium salt or a germicidal organic sulfonate, treated to to chemically bind the germicidal cation or anion of the salts to the protein-containing base material.

The invention relates to materials such as threads that have long lasting germicidal properties and processes for their manufacture.

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Attempts have already been made in various ways to be germicidal Manufacture general and special purpose materials. For example, in the United States patents 861 231, 1 741 893 and 2 75I 910 procedures for the introduction of Germicides in surgical sutures are described. In US Pat. No. 1,942,061, the introduction described a germicidal agent in bandages. Other patents describe the introduction of germicides Agents in textiles in general and in special articles such as toothbrushes, diapers, sanitary towels, blankets, Garments, paper, leather and the like .. For various purposes, the germicides should be particularly strong The base material should adhere to prevent rapid leaching, but the germicidal agent should not be so tightly bound be that thereby the germicidal effect is lost. The difficulty is to find workable procedures for To find such materials with long-lasting germicidal properties »

US Pat. No. 3,388,704 describes threads with sustained microbiological effectiveness by introducing certain germicidal agents into the thread body, which are introduced with the aid of a solvent which swells the thread. After removal of the solvent, the germicides are included in the thread for slow release. It has also been proposed (US Patent Application 648,247), the germicide or other materials by manufacturers · ,, position of substantially water Netherlands * ^ _r *, the germicide beat in the thread in the Fädeii..fin.rv close. - .. --- ■ - ■ ■,. , - _; , .--. _: .- _v _ _{/ y :: s} a

According to the invention, threads and others are obtained. ' Materials ^ of a certain kind with sustained germicidal effectiveness without swelling after the solvent up or

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must be worked according to the precipitation method. It it was found that certain documents or basic materials that can be processed into everyday objects through chemical compound of the base with a germicidal material with long-lasting germicidal properties can be. According to the invention, a nitrogen-containing organic is amphoteric, film-forming or fiber-forming Base material treated with an aqueous solution of a germicidal salt with at least one germicidal ion, whereby the ions come into intimate contact with the base material and the germicidal ions are chemically bound to the base material. The type of formed chemical Bond is unknown. The presence of the chemical bonds is indicated, however, by the fact that excess Proportions of germicidal agents that exceed a certain fixed amount (that of the base material and the in Question standing ion depends) are taken up by the base material, can be easily extracted by washing with water ^ while proportions below a certain amount cannot essentially be extracted. The type of bond is not known. However, the bond is not firm because the base material has a persistent germicidal effect, which is due to the slow release of the germicidal material.

The basic material that is made germicidal according to the invention is an amphoteric, nitrogen-containing organic, film or fiber-forming material. Preferred base materials are film-forming fiber-like proteins or organic polymers. Of the fibrous proteins, collagen and the silk protein fibroin are preferred. Organic polymers such as polyvinyl pyrrolidone, the amphoteric ones, are also suitable Have properties.

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The objects treated are preferably films and textiles, including threads, fibers, yarns, fabrics, Fiber fleece, etc. as well as finished items such as sutures, Bandages, etc. The invention is particularly useful for making threads from silk and collagen with long lasting germicidal properties suitable.

The germicidal ion intended for the raw material can be either a cation or an anion. The inven-

ψ proper raw materials are amphoteric. This means that in their normal form they can react with both anions and cations. The germicidal ion is obtained by dissolving a germicidal salt in an aqueous solution. Suitable cationic germicidal salts are germicides with quaternary ammonium groups. The water-soluble quaternary ammonium compounds with a germicidal effect are cationic salts which are particularly suitable according to the invention. Examples of such salts are substituted and unsubstituted alkyl dimethyibenzylammonium halides such as diisobutylphynoxyethoxyethyl dimethylbenzylammonium chloride (Behzäthonium chloride), benzalkonium chloride, lauryldimethylbenzylammonium chloride, dimethylbenzylammonium chloride, cetylammonium chloride.

"Chloride and pyridine salts such as lauryl pyridinium halides.

The water-soluble quaternary ammonium salts are made from Compounds of the general formula:

XL

N-E ¹

selected, may be in which X is an _anion; ~ that does not make the salt insoluble in water, e.g. chloride, bromide, sulfate

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etc. R represents an aliphatic hydrocarbon chain having at least 8 carbon atoms which, together with other H 'radicals, are part of a heterocyclic system can, These hydrocarbon chains are preferred by oxygen, double bonds, nitrogen or aromatic Rings interrupted. The radicals R 'are lower alkyl radicals with 1 to 7 carbon atoms, aralkyl, alkenyl, alkoxy, Polyalkoxy or chloroalkyl radicals.

The germicidal ion can also be an anion, for example the anion of a sulfonamide or its derivative, salts of hexachlorophene or other germicidal anions or anions of anionic surfactants or of organic acids. Anionic germicidal surfactants are organic sulfonates such as alky-sodium sulfonates, aralkyl-sodium sulfonates, monosulfonates of monoglycerides, sulfonates of succinic acid esters, etc. The term "organic acid" denotes organic compounds which contain acidic functional groups which form salts with bases, e.g. ammonium and alkali hydroxides . The term therefore also encompasses organic compounds which contain other functional groups such as the hydroxyl group and which react with the bases via the acidic functional group in order to form the water-soluble salts. Among the many organic acids that contain a suitable germicidal anion are the acidic antibiotics such as penicillins and pumagillin.

Suitable germicidal anionic surface-active agents are, for example, germicidal alkyl sulfonates of the general formula R-SCU-X, in which R is an alkyl radical having 13 to 18 carbon atoms and X is sodium or potassium , germicidal alkaryl sulfonates of the general formula R-Ar-SCU-X, in which R is an alkyl radical with 10 to 18 carbon

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atoms, X sodium or potassium and Ar a divalent one aromatic hydrocarbon radical mean monosulfates of Monoglycerides and sulfonates of succinic acid esters. Particularly suitable anionic surface-active agents are in particular dioctyl antrium sulfosuccinate, sodium lauryl sulfate, Sodium tetradecyl sulfate, sodium alkyl phenoxy sulfate and triethanolamine lauryl sulfate salts of fatty acids such as triethanolamine lauryl sulfate.

The ionic salts with a long-lasting germicidal effect can be incorporated into all of the nitrogen-containing raw materials mentioned. The base material is simply treated with an aqueous solution of the germicidal salt. The aqueous solution can contain a swelling agent that facilitates penetration into the base material. The swelling agent can be the water of the aqueous solution or an additional component such as a polar organic solvent. The solution can be heated to facilitate impregnation, but the germicidal salt must not be destroyed by the heating.

The germicidal ions can * your in garments such as Win · Wundverfeände and sutures _t be introduced at least partially contain the aforementioned nitrogen-containing base e.

The invention is illustrated in the following examples. Example 1 '

A silk thread of about 1g is dissolved in 100ccm of an aqueous solution with a content of 20% by weight of benzethonium chloride at room temperature. The solution is then heated to 100.degree.

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warms and kept at this temperature for 15 minutes. Of the The thread is then taken out of the solution and washed several times with several liters of water. The thread is removed at intervals dried and weighed. It was found that after a few rinses the thread weight was essentially remains constant and that further thorough washing with Water does not bring the weight below about 1.06 g. This corresponds to an uptake of around 6%.

The sustained germicidal effectiveness of the thread is demonstrated by exposing the thread to a microorganism such as bacillus subtilus is brought into contact. Even after several times Washing will keep the area around the thread clean. The sustained microbiological effectiveness was also demonstrated in mice shown. The threads treated according to the invention were e.g. 5 days "transplanted into * mice and showed" no growth of Organisms when 'removed from the mice and placed in a' culture medium. '

Example · '2''"^:;;' ■ ■ - '- ■. ■ - ·: ■

A silk thread is treated with an aqueous solution of benzalconium chloride at room temperature and washed until% fat% eW'essehe '''is"essentially ¹ constant ^c b'e1iP about"ψά'". The 'deterrent "germicidal action * - all" is shown "as in" Example 1. "* - · - - '^;

Example 3

A collagen thread is bound with about 6% benzethonium similar to Example 1 with the exception that the collagen thread is previously pre-swollen in an aqueous glycerol solution; "Öa'l '^ Beitiiätliöftium' is very ^: difficult to get out of the thread

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to wash. A sustained germicidal effect is obtained as in the previous examples.

Example 4

A braided silk thread is swollen in hot water for 15 minutes and immersed in a 1% solution of benzethonium chloride for 15 minutes at room temperature. The thread is then dried with blotting paper, washed in hot water for 10 minutes and dried. The proportion of germicidal benzethonium was calculated to be about 2%. It was difficult to wash out and the thread shows persistent germicidal activity.

Example 5.

A silk thread is swollen in boiling water for 15 minutes and hung in a 1% solution of neomycin sulfate for 10 minutes at room temperature. The thread shows like that of the previous examples show sustained germicidal effectiveness.

As mentioned above, the base material or the sub-) could be a textile material that is in the form of fibers, threads, yarns, or finished articles. The fiber material can be a natural or synthetic material. The invention is applied to garments, blankets and others and non-woven products, as well as yarns, threads, and bandages and the like. In addition to the examples mentioned Materials, the backing can be other proteinaceous products and other amphoteric nitrogen-containing organic polymers contain. The invention is particularly suitable for non-absorbent threads and other articles made of materials such as silk, which are not absorbed by the guest body.

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The maximum amount of the remaining germicidal ions in the base that can be introduced varies somewhat depending on the Raw material. Shares in excess of the amount that is chemically combined with the base material can be provided are and are desirable when a high dose of germicidal agent is initially beneficial. In general, the A minimal amount of a long-lasting germicidal agent should usually be chosen, but trace amounts of only 0.1% by weight, based on the weight of the fiber, effective. Though more antibacterial material can be introduced in some cases, but this is generally not practical, since even smaller amounts result in the desired lasting antibacterial effectiveness. The preferred amount of the chemically bound antibacterial material is therefore between 0.1 and 15% by weight, based on the weight of the original raw material.

The persistent germicidal effectiveness of materials that associated with insoluble germicidal salts according to the invention is proven when treated according to the invention Bringing materials into contact with organisms such as Bacillus subtilis, for example as in the examples. Even after repeated washing, e.g. the areas around a silk thread containing benzethonium, for example, remain free of the organisms. Similarly, the persistent germicidal nature of the thread in in vitro tests in mice to be shown. If, according to the invention, for example, silk threads treated with benzethonium stearate are planted in mice after 5 days when they are removed and placed in a culture medium, they show no growth of organisms.

As already mentioned above, the basic substances which are suitable according to the invention are, or otherwise, essential. Example

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wise contains the fibroin protein of silk in its normal Salt form free amino groups and free carboxyl groups. Many of these groups are undoubtedly in the salt form, since the Protons of the carboxyl groups were transferred to the basic amino groups. Lie in the presence of strong acids however, undissociated carboxyl groups are also present, and the amino groups are free in the presence of strong acids. the Proteins are therefore amphoteric electrolytes. In the presence of acids, the proteins are therefore in the form of acid salts that are cationic compounds. In this form, ™ the proteins preferentially bind with anions, for the introduction of anionic germicidal ions into the base material it is therefore preferred according to the invention to carry out the process in a medium with a pH value below the isoelectric Perform punkbes so that the protein in Form of its acid salt is present. If one wants to introduce a cationic germicidal ion, that is the procedure preferably at a pH above isoelectric Point through.

When using silk as a base, particularly when an anionic germicidal agent to be introduced into the silk K, rubber is preferably used with Entgummierungsmitteln that can be easily washed off from the silk, from the silk. Silk is usually degummed with soaps that contain palmitates, stearates and oleates, which can interfere with the subsequent chemical association of the silk with the germicidal ion. The silk is therefore preferably degummed with a low molecular weight, easily soluble alkaline material and inorganic bases. Alkali salts of low molecular weight organic acids with no more than 10 carbon atoms such as sodium acetate, ammonium hydroxide etc. are preferred.

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bringing the germicidal ion sterilized. It is also possible to use other ions in addition to the germ, to put killing ion and it is also possible to add cationic and anionic germicides to the base material. For example, according to the invention, heparin ions can be introduced thereby into silk or another base material be that one 'treats the base material with an aqueous heparin solution. This way, the raw material becomes with anticoagulant and germicidal properties. One can use any combination of anionic and Provide cationic germicides with a base by mixing the base with aqueous Solutions thereof treated as described in the examples.

According to the invention, protection against infections is also achieved in wounds. For example, any suitable Basic material of the type mentioned above in the form of a fabric or film or the like. to prevent infection can be used by making a wound incision with one or more layers of the treated film or tissue covered when the wound is closed. After suturing the pertinoneum, the wound surface is covered with a layer of treated base material, e.g. with an absorbable collagen film or silk fabric. The association is in sewn in the usual way. This dressing is then covered with a layer of the treated fabric or film. The skin is then sutured and another layer of the treated tissue or film is placed over the wound.

The toxicity of germicidal anionic and cationic surfactants is well known. Since the However, chemically bound materials are generally insoluble and because the bulk of the in the body is in the form

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a thread or wound closure fabric Material is very small, there were toxic amounts of the materials never ascertained. For example, if a total amount of thread of 1g is required, the maximum amount is of germicide 150 mg · Even if this material would not be chemically bound and would quickly reach the point of introduction If the adjacent surface were released, no toxic levels of the germicidal ions would be reached. According to the invention, however, the materials are chemically bonded to the substrate and are therefore only very slowly over submitted for a period of days. In general, the germicidal ions according to the invention are very slow, preferably dispense at a rate of no more than about 1 or 2 mg per hour. Hence the concentrations are of germicidal material well below a level that would cause any toxicity problem.

Expectations /

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Claims (12)

Expectations 1. Procedure for rendering objects germicidal, characterized in that one objects, the amphoteric, nitrogen-containing ^ organic film-forming Contain material with an aqueous solution of a germicidal salt with at least one germicidal ion treated from germicidal amines or germicidal cations of quaternary germicidal ammonium compounds and the solvent is then removed from the article. 2. The method according to claim 1, characterized in that the solvent is washed out and then drying the object. 3 · Method according to claims 1 and 2, characterized in that the treated object is a thread. 4 ·. Process according to Claims 1 to 3, characterized in that the organic material Faaer-like protein or organic polymers are used will. 5. The method according to claims 3 and 4, characterized characterized that as an organic material Silk, collagen, or polyvinylpyrrolidone is used. 6. The method according to claim 1, characterized that the object is silk, which is by treatment prior to the treatment with the aqueous solution with an aqueous solution of an inorganic base or K 3207 / June 16, 1969 ₉₀₉ 882/16 the alkali salt of an organic acid with not more than 10 carbon atoms is degummed. 7. Article with long-lasting germicidal properties, consisting of a base made of a nitrogenous amphoteric organic film-forming material to which germicidal ions are composed of anions or cations of quaternary germicidal ammonium compounds are chemically bound. 8 .. Object according to claim 7 »characterized in that the base is fibrous Contains proteins or organic polymers. 9. Object according to claims 7 and 8, characterized characterized in that it has the shape of a thread and in particular made of silk, collagen or polyvinylpyrrolidone consists. 10. The article according to claims 7 "and 8, characterized in that it contains alkyldimethylbenzylammonium, substituted alkyl-dimethyl- _; benzylammonium or alkylpyridine as the cation * 11, article according to claims 7 and 8, characterized ur ch that it is as. Contains anionic acid antibiotics from the group of penicillins or fumagillin. 12. Object according to claims 7 and 8, characterized characterized dass.er an anion of a germicidal surfactant contains « K 3207 / 16.6.1969 909882/16 3 2