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Title:
METHOD OF PROCESSING A THREAD ESPECIALLY FOR MEDICAL USES
Document Type and Number:
WIPO Patent Application WO/2011/035989
Kind Code:
A2
Abstract:
The invention refers to a method of treating thready materials, especially useful for medical uses, such as production of sutures and the like. The method essentially consists in impregnating a thread of fibres with a solution of collagen containing an antiseptic component consisting of a nanodispersion of bentonite powders modified by intercalation of ions of Ag+ and/or Cu2+ and successively drying. The amount of said metals in the bentonite powder is of 2-8% by weight. The ratio between the ions of Ag+ and Cu2+, when both present, is of 1 : (0,3-0,5). The threads obtained have prolonged antimicrobic properties versus a wide spectrum of gram-positive and gram-negative microorganisms and a decreased toxicity. Moreover they have improved absorpion capacity.

Inventors:
BARBAKOV VLADIMIR ILYCH (RU)
BEKLEMYSHEV VIACHESLAV IVANOVICH (RU)
BEKLEMYSHEVA EVGENIYA FEDOROVNA (RU)
MAKHONIN IGOR IVANOVICH (RU)
MAUGERI UMBERTO ORAZIO GIUSEPPE (IT)
MESHKOVA IRINA MIHAILOVNA (RU)
SOLODOVNIKOV VLADIMIR ALEKSANDROVICH (RU)
Application Number:
PCT/EP2010/061994
Publication Date:
March 31, 2011
Filing Date:
August 17, 2010
Export Citation:
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Assignee:
INST APPLIED NANOTECHNOLOGY CSC (RU)
FOND SALVATORE MAUGERI CLINICA DEL LAVORO E DELLA RIABILITAZIONE I R C C S (IT)
SIB LAB LTD (MT)
BARBAKOV VLADIMIR ILYCH (RU)
BEKLEMYSHEV VIACHESLAV IVANOVICH (RU)
BEKLEMYSHEVA EVGENIYA FEDOROVNA (RU)
MAKHONIN IGOR IVANOVICH (RU)
MAUGERI UMBERTO ORAZIO GIUSEPPE (IT)
MESHKOVA IRINA MIHAILOVNA (RU)
SOLODOVNIKOV VLADIMIR ALEKSANDROVICH (RU)
International Classes:
A61L17/00
Domestic Patent References:
WO2009110940A22009-09-11
Foreign References:
RU2341602C12008-12-20
RU2309768C22007-11-10
US4024871A1977-05-24
RU2076740C11997-04-10
RU2330673C12008-08-10
Other References:
TONG G ET AL: "Antibacterial effects of the Cu(II)-exchanged montmorillonite on Escherichia coli K88 and Salmonella choleraesuis", VETERINARY MICROBIOLOGY, ELSEVIER BV, NL, vol. 105, no. 2, 31 January 2005 (2005-01-31), pages 113-122, XP004700892, ISSN: 0378-1135, DOI: DOI:10.1016/J.VETMIC.2004.11.003
Attorney, Agent or Firm:
GERVASI, Gemma et al. (Corso di Porta Vittoria 9, Milan, IT)
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Claims:
CLAIMS

1 . Method of treating thready materials, in order to confer to them a prolonged antimicrobic activity, comprising the steps of impregnating the thread with a water nanosystem of collagen containing as the antimicrobic substance a nanodispersion of at least one bentonite powder, modified by intercalated cations of Ag+ and / or Cu2+ and then drying the same.

2. Method according to claim 1 , wherein the bentonite powder contains 2,0-8,0% by weight of intercalated cations of Ag+ and / or Cu2+.

3. Method according to claim 1 , wherein the ratio between the bentonite powder intercalated with Ag+ and the bentonite powder intercalated with Cu2+ is of 1 : (0,3-0,5).

4. Method according to claim 1 , wherein the dispersiveness of nanoparticles of bentonite powder is of no more than 150 nanometers.

5. Method according to claim 1 , wherein the water nanosystem contains as the main components collagen in the amount of 0,5-4% by weight, bentonite powders in the amount of 2-8% by weight, the rest being water.

6. Method of treating thready materials according to claim 1 , wherein the amount of the water nanosystem used for impregnating the thread is no more than 50% b. weight with respect to the weight of dry thread.

7. Method according to claim 1 , wherein the water of the nanosystem is deionized water.

8. Threads for medical use, having prolonged antimicrobic activity in respect of a wide spectrums of gram-positive and gram-negative microorganisms and a decreased toxicity, obtained by impregnation of a thread with a water nanosystem of collagen containing as the antimicrobic substance a nanodispersion of at least one bentonite powder modified by intercalated cations of Ag+ and / or Cu2+, and by successive drying.

9. Threads according to claim 8, impregnated with an amount of water nanosystem not higher than 50% b.w. with respect to the weight of the dry thread.

Description:
METHOD OF PROCESSING A THREAD ESPECIALLY FOR MEDICAL USES.

Field of the invention

The invention concerns a technology of processing thready materials in light industry. State of the art

A method and a composition for processing a yarn is known (Russian patent RU 2341602). The composition for processing a yarn from polyester fibres contains polyethylene glycol, glycerin and ethanol. The composition provides a high coefficient of coupling of fibres in a yarn (factor of static friction) and a low coefficient of friction of the yarn processed in a solution in contact with metal parts of machines (factor of sliding friction). However the given method and composition are not suitable for the purposes of the present invention, which are stated hereinafter.

A processed thread (Russian patent RU 2309768) consisting of a polyamide twisted or braided suture with a cover having as additive a medical product, is known. The cover consists of Chitosan and as the medical product an antibiotic and biologically active substances on the basis of a biomass of plants of Araliaceae kind, or monohydrate-1 -hydroxygermatran and an antitumoral preparation. The known patent describes the combined biological action on a wounded surface. However the inconvenience of the given patent is the narrow area of activity of the medical products included in the preparation.

A method of processing a thread by impregnation with antimicrobic substances, drying and subsequent application of a polymeric cover is known (US Patent 4024871 ).

The negative aspect of this method resides in that the antimicrobic substance is separated from the polymeric cover and as a result antimicrobic action of the suture is rather limited.

A method of processing a suture is also known from a Russian patent (RU 2076740), a patent which constitutes the closest prior art for the present invention. The method described in said patent consists in impregnating a silk suture with a 3% collagen solution, drying the suture after its impregnation and successively impregnating the collagen with the antimicrobic substance beta-(5-nitrofuryl-2)- acrolein. Said known patent provides a high coefficient of impregnation (coupling) of a solution in the thread so decreasing its hygroscopicity and capillarity while at the same time obtaining a favourable smoothness of the thread, due to the use of a collagen solution. It is obtained a decrease in the coefficient of friction at interaction of the thread with tissues of living organisms. The specified characteristics are essential for manufacturing a suture material from the given thread.

However processing of a thread, in particular a surgical thread, with the collagen modified with an antiseptic preparation of beta-(5-nitrofuryl-2)-acrolein, which is a derivative of nitrofuran group, can provide a sensitization of the skin when using the given suture material. This indicates a most likely limited biocompatibility of the given preparation with tissues of various animals and human beings, because nitrofurans have strongly pronounced specific sensitivity. In particular, white mouse, porpoises, rabbits and calves are extremely sensitive to them.

Besides, the process of obtaining beta(5-nitrofuryl)-acrolein is based on the synthesis of furazidin and furakrilrin, what increases the costs for modification of a thread and thus increases the costs of all processes of processing a thread as a suture material. Disclosure of the invention

A positive technical result of the invention is to obtain prolonged antimicrobic properties in respect of a wide spectrum of gram-positive and gram-negative microorganisms and also adsorptive properties of a thread with simultaneous decrease in its toxicity and in the costs of the technological process of production. Said positive technical result is achieved due to the method of processing a thread consisting in impregnation of the thread with a solution of collagen containing an antimicrobic substance and subsequent drying in which, according to the invention, a water nanosystem on the basis of collagen with a nanodispersion of at least one bentonite powder modified by cations Ag + and/or Cu 2+ was used for impregnation of a thread, in an amount of these metals in the bentonite powder of 2,0-8,0% b.w.. The components are present in the nanosystem in the following ratio (% by weight):

collagen 0,5- 4

bentonite powder 2-8

water the rest, No more than 50% b.w. of the named nanosystem, with respect to the weight of a dry thread, is applied for impregnation.

The method is characterized also by a dispersiveness of nanoparticles of the bentonite powder of no more than 150 nanometers.

The method is characterized by application of a mix of nanoparticles of bentonite powders modified by ions of Ag + and Cu 2+ , with a content of the named metals in the mix of 2-6% b.w. and a ratio of the bentonite powders of 1 ÷ (0,3-0,5). Deionized water is used for obtaining a water nanosystem.

Detailed description of the invention

By realization of the present invention it is provided an antiseptic processing of a thread, with obtaining of prolonged antimicrobic properties concerning a wide spectrum of gram-positive and gram-negative microorganisms, and also adsorptive properties of the thread and simultaneous decrease in its toxicity.

The technical result achieved in the present invention is explained in the following:

- use of a nontoxic biological matrix, on the basis of a water nanosystem of collagen for injection of the antiseptic agent, a nanodispersion of a bentonite powder modified by ions of the silver and/or copper. The collagen is a structure generating component for other active substances, whose action becomes stronger in the formed system;

- presence of a preparation on the basis of a water nanosystem of collagen with a nanodispersion of a bentonite powder modified by ions of silver or/and copper in processed system (the processed thread material and tissues of an alive organism). Ions of silver and copper are characterized by functional properties with a wide spectrum of antimicrobic activity on pathogenic microflora. The above mentioned preparation is safe ecologically and does not result in increase of sensitivity of tissues of live organisms;

- use of a mineralogical product, i.e. a nanodispersion of a bentonite powder, for impregnation of a thread. A bentonite powder is characterized by high sorption capacity of solutions and by reactions of ionic replacement in "interlayer" space of cations of metals with cations of other metals-assistants contained in a liquid basis of a processed material;

- use of the antiseptic agent as dispersive environment of nanoparticles of bentonite powders for impregnation of a thread in a structure. High specific surface of bentonite powders provides a big area of contact with the bacterial environment and increases efficiency of antimicrobic activity;

- use of synergetic compatible mixes of bentonite powders, modified with ions of the named metals in the declared invention;

- use of a preparation with low-cost antibacterial agent, on the basis of a mineral product, for impregnation of a thread according to the invention.

The analysis of the prior art did not reveal patents with the whole set of characteristics corresponding to what declared in the present application and able to realize the above described result of prolonging the action on antiseptic processing of woven materials used for manufacturing products for household and medical purposes.

The result of the analysis of the prior art testifies the conformity of the present patent application to criteria of "novelty", "degree of inventiveness" and "industrial applicability". This result is proved to be true by the description provided hereinafter.

Ready to use medical and labware commodity products and also known technological processes are used for realization of the invention, namely:

the collagen, i.e. a natural biological product obtained processing sawn-off pieces of raw hide derived from cattle; deionized water; the antiseptic preparation possessing antimicrobic and antifunguses properties (see Russian patent RU N. 2330673). Mineral raw material (bentonite in Na-form) is enriched with ions of Na + by its processing in water solution of sodium chloride with subsequent washing and filtering of the obtained semifinished product for removal of acid anions, as described in the named Russian patent. The obtained semifinished products are modified with a solution of inorganic salts of metal. For this purpose silver nitrate (AgN0 3 ) and copper sulfate (CuS0 4 ) are used. Then a retention time interval of modified bentonite in the specified salt solutions, and cleaning of modified bentonite from salts of sodium by its washing and filtration, is carried out. After drying the obtained preparation is grinded. It is established by titrimetric analysis of the preparation obtained according to the given known patent, that the amount of silver and copper in the obtained preparations corresponds to 2-8% b.w. of silver or copper, depending on the initial raw product and on the amount of activating and modifying reagents. The specified weight % content of silver or copper is optimum. Costs of manufacturing are increased at increase in amount of silver or copper in the modified powder of bentonite, while antibacterial activity of the product obtained according to the declared invention is decreased at decrease in weight % of the content of the named components. Use of a mix of the named nanodispersions of bentonite powders is preferable for decreasing the costs of manufacturing the described product according to the invention.

The mechanism of action of ions of metal, in particular silver, on a microbic cell, consists in absorption of ions of silver by the cellular capsule which has a protective function. The cell remains viable but its functions get broken (for example division i.e. bacteriostatic effect) as a result of which enzymes of the respiratory circuit of a cell are inhibited. Processes of oxidation and oxidative phosphorylation in microbic cells are separated and the cell perishes.

Realization of the present invention will lead to deterioration of the properties of a thread or to increase in costs for its production if some change in the composition of used components or in their specified ratio is performed.

Realization of the invention is illustrated but not limited by the following concrete examples:

Example 1 .

A thread was treated. A thread of silk was used. A water nanosystem on the basis of collagen with a nanodispersion of a bentonite powder modified (intercalated) by cations of Ag + at amount of silver in the powder of 2,0% b.w. and at the following ratio of components in the nanosystem (weight %) was used for impregnation of a suture:

collagen 0,5

bentonite powder 8,0

water the rest.

50% b.w. of the named nanosystem, with respect to the weight of a dry thread, was used for impregnation. Dispersiveness of nanoparticles of the bentonite powder was 150 nanometers. Deionized water was used. Example 2.

A thread was processed. A thread of silk was used. A water nanosystem on the basis of collagen with a nanodispersion of a bentonite powder modified (intercalated) by cations of Cu 2+ , with an amount of copper in the powder of 8,0% b.w. and the following ratio of components in the nanosystem (% b.w.), was used for impregnation of a suture:

collagen 4, 0

bentonite powder 2, 0

water the rest.

47% by weight of the named nanosystem, with respect to the weight of the dry thread, was used for impregnation. Dispersiveness of nanoparticles of the bentonite powder was 40 nanometers.

Example 3.

A thread was processed. A thread of silk was used. A water nanosystem on the basis of collagen with a nanodispersion of a bentonite powder modified (intercalated) by cations of Ag + and Cu 2+ with an amount of these metals in the powder of 7,0% b.w. and with the following ratio of components in the nanosystem (weight %) was used for impregnation of a suture:

collagen 2,0

bentonite powder 5,0

water the rest.

30% b.w. of the named nanosystem, with respect to the weight of the dry thread, is used for impregnation. Dispersiveness of nanoparticles of the bentonite powder was

145 nanometers. Deionized water was used.

A mix of nanoparticles of bentonite powders modified by ions of Ag + and Cu 2+ , with a total content of the named metals of 2% b.w., in a mix of the two powders in a ratio of 1 ÷0,3, was also used for impregnation according to the present examples.

Example 4.

Antiseptic processing of a thread was carried out. A thread from silk was used. A water nanosystem on the basis of collagen with a nanodispersion of a bentonite powder modified (intercalated) by cations of Ag + and Cu 2+ , with an amount of these metals in the powder of 5,0% b.w. and the following ratio of components nanosystem (% b.w.), was used for impregnation of the suture:

collagen 2,0

bentonite powder 5,0

water the rest.

The named nanosystem was used in the amount of 30% b.w., with respect to the weight of the dry thread, for impregnation. Dispersiveness of nanoparticles of the bentonite powder was 145 nanometers. Deionized water was used.

A mix of nanoparticles of bentonite powders, modified by ions of Ag + and Cu 2+ , with a total content of the named metals of 6% b.w., at a ratio of their powders in the mix of 1 ÷0,5 was also used in the given example.

After impregnation of the threads (examples 1 -4) drying was carried out. As a result of drying silk threads collagenated by the specified nanosystem have a smooth and uniform surface. The threads acquired monofilament structure due to gluing of separate fibres by collagen.

In determining the correct parameters for impregnation of a thread, the inventors ascertained that the increment of weight of a suture after impregnation should not exceed 2% by weight, under favourable conditions of processing of a suture.

1 g of a suture - 100%

a nanosystem - 40 %

0.4 gr. of the nanosystem - 100%

the increment of weight is not more 2%

Total: collagen + powder = 0,008 g

Powder - 5% Total powder - 0,0004 g Total: collagen - 0,0076 g

In total the increment of weight of the thread was of 0,8 % b.w. after impregnation. The effective antimicrobic processing of threads is provided as a result of impregnation of a thread with the specified water nanosystem containing as antiseptic agent a bentonite powder intercalated by the named ions of metals. It is based on activity of ions of these metals in respect to various microorganisms. Besides prolonged antimicrobic properties, the silk thread gets also the biological properties inherent to collagen and capable of stimulating reparative processes in sewed tissues. Thus, according to the declared method, a thread (a fibrous material) is processed for obtaining specified properties, i.e. antimicrobic properties concerning a wide spectrum of gram-positive and gram-negative microorganisms. Moreover the impregnation of a thread with a collagen solution that provides decrease in hygroscopicity and capillarity, reduces the possibility of further infection what is essential for a thread.

It is important that a bentonite powder be injected in a collagen nanosystem because a stage-by-stage processing of a thread (processing with a collagen solution and subsequent processing with an antiseptic preparation on the basis of a hydrosol of a bentonite powder) worsens adhesiveness of a preparation to the surface of a thread, due to certain properties obtained already at the first stage, i.e. decrease in hygroscopicity and smoothness (decrease in coefficient of friction of a fibrous material at interaction with other materials).

Sutures obtained by the examples 1 -4 were tested with the purpose of determining their mechanical properties when exposed at long action of moisture, in particular the following parameter: rupture loading - ultimate tensile stress (kgf).

The threads were kept in distilled water over 10 days, at 20°C, for estimation of behaviour. As a result of the tests it was established that the increment of weight of the threads, produced in the specified examples, does not exceed 2% b.w., what testifies the efficiency of the used composition for impregnation of sutures.

Rupture loading - ultimate tensile stress (the most sustained force kgf):

- for dry sutures before impregnation, at diameter of the samples of 0.044 (mm)- 120;

- for dry collagenated threads (examples 1 -4), at their diameter of 0.0444 (mm)- 170;

- for moist collagenated threads (examples 1 -4) at their diameter of 0.045 (mm) -160. It follows from the resulted data that impregnation of the threads according to the examples 1 -4, only insignificantly increases diameter of a thread, while appreciably increases ultimate tensile stress of threads in dry and moist conditions.

The estimation of the antiseptic properties of the threads obtained by the examples 1 -4 was carried out by their biotesting for antimicrobic properties, after subjecting them to immersion intervals in distilled water. Estimation of antimicrobic properties was carried out by a standard technique by using a culture of Staphylococcus aureus (the most widespread culture for determination of antimicrobic properties). The culture has been obtained in the environment of beef-extract agar (BEA) after 24 hours at the temperature of 37°C. Homogeneous suspension of cells in deionized water was then prepared. The prepared composition, in the amount of 1 ml of suspension, was brought in Petri's cups with a dried BEA environment and was uniformly allocated on a surface of environment by a sterile spatula for germination of culture in a dense lawn. Then slices of the threads processed according to the examples 1 -4 were imposed on the surface of agar by a sterile tweezers. Cups seeded with samples were thermostatically controlled at 37°C. Antimicrobic properties of the threads were determined by formation of zones of inhibition of growth of strain of Staphylococcus aureus, which were precisely allocated on the background of a dense lawn of growth of tested culture. As a result of the tests the presence of significant zones of inhibition was established in the threads impregnated with compositions according to examples 1 -4 and their absence was established in the not impregnated sample of a suture, which was not exposed to immersion interval in distilled water.

Thus, the carried out tests testify as a whole the efficiency of the method described with the present invention, for antiseptic processing of a thread.