RU2309768C2 - Surgical suturing material (variants) - Google Patents

Abstract

FIELD: medicine, surgical materials.

SUBSTANCE: the present innovation deals with surgical suturing material that includes ligature consisting of the nucleus out of polyamide twisted or woven ligature with membrane out of chitosan at addition of antibiotic as medicinal preparation; it has been described surgical suturing material that includes ligature consisting of the nucleus out of polyamide twisted or woven ligature with chitosan membrane with addition of antibiotic preparation and biologically active substances based upon the biomass of Aralia-group plants or monohydrate-1-hydroxygermatran; it has been suggested surgical suturing material that includes ligature consisting of the nucleus out of polyamide twisted or woven ligature with chitosan membrane with addition of antibiotic preparation, biologically active substances based upon the biomass of Aralia-group plants or monohydrate-1-hydroxygermatran and anti-tumor preparation. The innovation provides combined biological action upon wound surface and favors rapid treatment and healing of wounds.

EFFECT: higher efficiency.

3 cl, 19 ex, 1 tbl

Description

The invention relates to medicine and relates to surgical suture materials.

Suture material is an integral part of any operation. The outcome of an operation, especially complicated, largely depends on the quality, chemical composition, biocompatibility, structure of suture material, the reaction of surrounding tissues to it.

Known biologically active suture thread, which is a polyamide thread containing antibiotic, antimicrobial, immunomodulating, antitumor compounds (Pat. WO 0240069, A61L 17/00 publ. 05.23.02). Suture strands impregnated with one or more of these compounds are placed in the body, including directly into the wound, with surgical intervention to ensure therapy (part of the course in the treatment of a disease or disorder).

The disadvantage of this thread is the method of introducing biologically active compounds through prolonged impregnation with aqueous solutions of drugs, which does not allow the components of the modifying solution to firmly fix on its surface. In addition, the thread is used only as a carrier of biologically active compounds, and not medical suture material, the main function of which is the bonding of wound surfaces, preventing the divergence of the edges of the wound.

Known suture material, which is a thread of polyamide PA-6, sequentially coated with a shell of polyvinyl alcohol with a thickness of 5-50 microns and a shell of chitosan with a thickness of 5-30 microns (Pat. RU 20073528, A61L 17/00, publ. 02.20.97 g .).

The disadvantage of this material is the lack of biological activity in relation to both wound infection and tumor pathology. Another disadvantage of the material is a complicated method for its preparation, and the removal of the sizing agent by extraction with organic solvents is not technologically advanced and undesirable for medical devices.

As a prototype, the authors propose an antimicrobial suture surgical suture, which includes a polyamide suture, which is a core of twisted or braided polyamide suture with a sheath of E-caprolactam copolyamide and hexamethylene diammonium adipate containing a drug supplement [Pat. RU 2237494, А61L 17/00, А61В 17/06, publ. 10/10/2004].

The disadvantage of this thread is that in the first day of operation of the thread, up to 90% of the administered drug is released from it, which leads to a reduction in the time required for the manifestation of the biological effect.

A known filament has a weakly expressed or completely absent antitumor effect. In addition, the thread has insufficient manipulation properties, has a relatively high stiffness, which complicates the knitting process into a knot.

The technical task of this invention is the creation of suture surgical material with increased time of combined biological action: antitumor, antimicrobial, activating proliferative and reparative function, as well as having better physical and mechanical properties.

The problem is solved in the present invention due to the fact that the suture surgical material according to option 1 includes a thread consisting of a core of twisted or braided polyamide filament with a sheath of chitosan with the addition of a drug - antibiotic in the following ratio, wt.%:

Polyamide thread 73.0-99.75 Chitosan 0.2-20.0 Antibiotic 0.05-7.0

In option 2, the suture surgical material includes a thread consisting of a core of twisted polyamide or braided thread with a chitosan sheath with additives of biologically active substances based on biomass of plants of the aralia family or monohydrate-1-hydroxyhermatran and antibiotic in the following ratio of components, wt .%:

Polyamide thread 58.0-99.7 Chitosan 0.2-20.0 Biologically active substances based 0.05-15.0 biomass of plants of the aralian family or 1-hydroxyhermatran monohydrate Antibiotic 0.05-7.0

In option 3, the suture surgical material includes a suture consisting of a core of twisted polyamide or braided thread with a chitosan sheath with the addition of drugs - biologically active substances based on biomass of plants of the aralia family or monohydrate-1-hydroxyhermatran, antitumor drugs and antibiotic in the following ratio components, wt.%:

Polyamide thread 43.0-99.65 Chitosan 0.2-20.0 Biologically active substances based 0.05-15.0 biomass of plants of the aralian family or 1-hydroxyhermatran monohydrate Anticancer drug 0.05-15.0 Antibiotic 0.05-7.0

The proposed suture surgical material allows you to solve the problem.

The execution of the shell of the thread from chitosan is multifunctional:

- performs the function of a “carrier” and a local “donor” of delayed action of drugs;

- Gives the polyamide yarn properties of a monofilament compact yarn with a smooth atraumatic surface and non-fibrous ends;

- enhances the effect of drugs.

The use of twisted or braided polyamide yarn as a core allows to increase strength and reduce elongation of the finished yarn, which makes it more convenient to use.

As a polymer coating, water- and acid-soluble chitosan is used.

Chitosan is one of the derivatives of the natural polysaccharide-chitin. The unique characteristics of chitosan (the ability to fiber and film formation, ion exchange, complexation, as well as physiological activity in the absence of toxicity) make it possible to create materials with a wide range of uses, unique in their properties, in combination with various synthetic polymers, including medical.

The creation of medical-grade materials based on chitosan has favorable prospects due to the low toxicity, bio- and hemocompatibility, biodegradability of this natural polymer, as well as the presence of reactive groups providing the possibility of its chemical modifications.

It is known to use chitosan to obtain polymer coatings when encapsulating drugs, for example aspirin, indomethacin, papaverine, testosterone hydrochloride. Chitosan improves the absorption and effectiveness of sparingly soluble dosage forms and helps to prolong their action. The use of chitosan gel provides a reliable acceleration of the skin regeneration process in wound diseases. In oncology, chitosan is used to transport drugs, mainly cytostatics, including fluorouracil (V.M. Tsygan, K.D. Zhogolev. Market of dietary supplements, 2, 2002, p. 3-9).

The sorption regenerating, immunomodulating and antimicrobial properties of chitosan itself are known, as well as its use for wound healing and anti-inflammatory film-forming compositions (Albulov A.I. Avtoref diss ... Doctor of Biological Sciences. Schelkovo, 2004, p. 28-29).

It is known to use chitosan and its derivatives for coating the surfaces of implants made of synthetic materials in order to eliminate immune reactions that could lead to their rejection (Pat. DE 19724865, publ. 24.12.98).

Chitosan as an anti-allergic agent is used when working with latexes and vulcanizers, as well as in rubber compositions in the manufacture of condoms (Application 19742318 Germany, publ. 01.04.99).

Chitosan has its own bactericidal activity. The most susceptible to chitosan are staphylococci, streptococci, fungi of the Candida series, gram-negative Helicobacter pylon, representatives of the genera Escherichia, Ehtrobalter, Citrobacter, etc. (V.M. Chervinets, V.M. Bondarenko, A.M. Albulov, B.A. Komarov Materials of the VI International Conference "New Achievements in the Study of Chitin and Chitosan", M. - Shchelkovo 2001, p. 252-254).

The introduction of biologically active substances (BAS) into the shell of a surgical thread based on the biomass of plants from the aralia family or monohydrate-1-hydroxyhermatran allows you to get a thread that has the ability to activate proliferative and reparative function, which affects the course of the wound process during surgical interventions and improves tissue epithelization.

It is known that the biomass of plants of the aralian family contains biologically active substances (BAS). There are various ways to obtain these biologically active substances, and technological methods and modes have a significant impact on the content and ratio of components extracted from plant materials, as well as their pharmacological activity (Muravyov I.A. Drug technology: In 2 vol. 3rd ed. M .: Medicine, 1980).

As biomass, natural aralia plants (ginseng, eleutherococcus) can be used, which are initial and subjected to various types of treatments (for example, “red ginseng”) and products obtained from selective strains of these plants (for example, Panaxel), including containing germanium organic compounds.

It is known to indicate its inherent pharmacological activity of ginseng root, the so-called "white ginseng", approved for medical use and suitable for storage (State Pharmacopoeia of the USSR. 11th ed. Issue 2: General methods of analysis. Medicinal plant materials. - M. : Medicine, 1990. S. 348-349).

Korean "red" ginseng is allowed for medical use; the color on the outside and at the break is reddish-brown. The method of obtaining it is not shown, the composition of the biologically active substances of the complex is not specified and the difference in its activity from that of the “white” root is not indicated (State Pharmacopoeia of the USSR. 11th ed. Issue 2: General methods of analysis. Medicinal plant materials. - M .: Medicine , 1990. P.349).

Panaxel ginseng biomass is obtained from selective strains of plants of the Araliaceae family, which is a medicinal product that can contain organic germanium compounds: Panaxel, dry biomass FSP 420166124101, valid until 06/01/2006 and Panaxel, tincture FSP 420166124001, valid until 06/01/2006

The content of the organic germanium compound additionally stimulates the regenerative processes in the tissues of the body (E.Ya. Lukevits, TK Gar, L. M. Ignatovich, V. F. Mironov. Biological activity of the compounds of Germany, Riga, Zinatne, 1990, 191) .

It is known that the main advantages of plant products and products based on their selective strains are determined by the combined effect on the body of a complex of biomass substances as a whole.

The general composition of biologically active substances based on the biomass of plants of the Aralian family has not been described; its activity has not been characterized.

The product has an increased glycoside content, but it is known that in addition to glycosides, the Aralia biomass contains a number of other biologically active substances, for example, polysaccharides (Hiromichi Okuda, Yinan Zheng, Yukinaga Matsuura, Takeshi Takaku, Studies on biologically active substances in non-saponin fraction of Korean Red ginseng / (Proceeding of the 6 ^th International Symposium. Seuol Korea, 1993. P.110-112).

The glycosides and water-soluble polysaccharides contained in the biomass of aralic plants also have an immunomodulating, hepatoprotective, anticarcinogenic and adaptogenic effect.

The anticancerogenic, antitumor, and antimetastatic effects of preparations of aralia plants and their selective analogs are known, due to the immunological, hormonal, and metabolic mechanisms of their action, and the presence of organogermanium compounds in them: 2-carboxyethylhermsesquioxone or 1-hydroxyhermatran enhances these properties ("Plant Resources" v.29 , issue 4, 1993, p.1-12).

As antitumor drugs, cytostatics fluorouracil, cyclophosphamide and sarcolysin are used, which are broad-spectrum antitumor drugs that are soluble in water. Fluorouracil is an antimetabolite of uracil involved in cell formation (M.D. Mashkovsky, Medicines, M., 2002, v. 2, p. 425). Fluorouracil contributes to the death of cells, especially rapidly dividing. Fluorouracil has long been widely used both directly in the chemotherapy of tumor pathologies and in the development of new anti-tumor dosage forms. There are methods for converting fluorouracil into various polymeric materials, including chitosan and its derivatives, to overcome toxicity problems and increase the duration of action of drugs.

Cyclophosphamide and sarcolysin are alkylating antitumor drugs. They are able to react with nucleophilic centers of protein molecules, disrupting the synthesis of DNA, especially of rapidly dividing cells. As well as fluorouracil, cyclophosphamide and sarcolysin are widely used in the preparation of new types of dosage forms, including for application to grafted synthetic fibers and threads (Yu.L. Zaikin. Abstract of the dissertation, Leningrad, 1985, p.9-11).

As antibiotics, doxycycline, ciprofloxacin, mitomycin, etc. can be used.

The introduction into the sheath of a surgical thread of an antimicrobial doxycycline, capable of forming a chemical bond with the free amino and hydroxyl groups of chitosan, contributes to the prolongation of its activity and, therefore, greater bactericidal activity.

Ciprofloxacin is a broad-spectrum antibacterial drug that has an anaerobic effect in relation to both gram-positive and gram-negative microorganisms. Ciprofloxacin is used for the prevention of infections during surgical interventions, as well as in the treatment of severe infections against the background of immunodeficiency (M.D. Mashkovsky. Medicines, M. 2002, v.2, s.296-297). The presence of polar amino and carboxyl groups in the ciprofloxacin molecule enables the formation of chemical bonds with the chitosan macromolecule.

Mitomycin is a broad-spectrum antitumor antibiotic. It is used in combination with fluorouracil for gastric adenocarcinoma and other malignant neoplasms, and has relatively weak immunosuppressive activity (M.D. Mashkovsky. Medicines, M, 2002, v. 2, p. 230). The presence of polar amino groups in the mitomycin molecule promotes the formation of chemical bonds with polymer coating macromolecules.

A polyamide twisted thread (TU 6-13-00209556-167-2002) or a polyamide braided thread (TU 17 RF 6-1085-84) with a linear density of 10-500 tex with the following physical and mechanical properties is used for a surgical suture:

Specific breaking load, gf / tex 45-55 Elongation at break,% 15-25 Preservation of strength in the node,% 60-75 Elongation at break in the node,% 12-20,

which, after applying a coating of chitosan and drugs in the above amounts on a thread, practically do not change.

For the shell, food chitosan is used (TU 9898-067-00047842-03) with a molecular weight of 30000-300000.

The content of chitosan in the sheath of the surgical thread is from 0.20 to 20 wt.%. With a higher chitosan content in the sheath, the thread becomes very stiff and injures the edges of the wound. The lower content of chitosan in the shell does not allow to achieve the necessary compactness of the thread.

The shell contains drugs: an antibiotic - doxycycline chloride, ciprofloxacin, mitomycin, an antitumor drug - fluorouracil, cyclophosphamide, sarcolysin, as well as a biologically active substance based on biomass of the aralia family or monohydrate-1-hydroxyhermatran. For the manifestation of the therapeutic effect of surgical filaments, it is sufficient to have an antibiotic of 0.05 wt.% Or an antibiotic and biologically active substances in a filament of 0.05 wt.%. A smaller amount of antibiotic and biologically active substances does not provide the necessary therapeutic effect. The increase in the content of biologically active substances in the thread is above 15, and the antibiotic above 7.0 wt.% Is impractical, because with an increase in their content, there is no further acceleration of the proliferative-reparative function of the thread and an increase in its antimicrobial activity.

For the manifestation of the antitumor effect, the content of the drug should not exceed 15 wt.%.

The obtained threads determine the mass content of the components in them, the parameters of the process of desorption of drugs into a model environment, antimicrobial activity and other biomedical properties, which are presented in table 1.

The study of the desorption of drugs in vitro was carried out under conditions simulating the release of drugs from the strand into the internal environment of a living organism.

For this purpose, 0.333 g of biologically active filament was placed in a test tube, after which 10 ml of model fluid (distilled water or 0.9% aqueous NaCl solution) was added. The tubes were placed in a heating cabinet and kept at a temperature of 37 ± 1 ° C for 1-30 days. The model solution was replaced daily with simultaneous sampling of the test material.

Analytically, according to previously developed methods, the determination of the content of the drug was carried out in the samples.

Then, the amount of the drug transferred from the yarn to the model medium was calculated as a percentage of the initially administered (P _rel ,%) according to the formula:

где

Where

R _p - the content of the drug in the original thread,%

R ^1-30 - the content of the drug in the thread after 1-30 days of desorption,%

The antimicrobial activity of the strands is determined by the in vitro method of agar plates to study the growth retardation radius of the test cultures Bacillus Subtilis L-12 (Bac / Sub), Staphylococcus aureus 906 (St.aureus) and Escherichia Coli K12 (E.coli), (Guide to microbiological and virological research methods / Edited by Birberg N.O., M., Medizdat, 1982).

The composition of the wound exudate is determined after 12 hours by cytological examination. The material is sampled according to the method of M.P. Pokrovskaya and M.S. Makarov (Wounds and wound infection: a guide for doctors / Edited by M.I. Kuzin, B.M. Kostyuchenok, M., Medicine, 1990, p. 38-223) by the manufacture of preparations - prints on slides.

The study of drugs is carried out under a light microscope with an increase in lens 90 using an ocular micrometer.

The antitumor activity of the suture samples was studied in vitro using an RD cell culture derived from human rhabdomyosarcoma and a HEP2 cell culture derived from human epidermoid carcinoma. In this case, pre-cultures with a freshly formed monolayer were microscopic to check the state of cells and labeled tubes (experimental and control). The germ medium (Eagle Medium MEM with a double set of amino acids + 500 thousand units of penicillin + 5% fetal serum) was removed and replaced with 1 ml of support medium (Eagle Medium MEM with a double set of amino acids + 500 thousand units of penicillin). Then, a piece of the studied suture material was placed in each tube of the experimental series or 0.2 ml of a solution of an antitumor preparation was added. All tubes were placed in an inclined position (5 °) in a thermostat at a temperature of 36 ° C. Daily cell cultures were checked for the appearance of a cytopathic effect (CPE) using a light-beam backward microscope (invert microscope). All signs of CPE (from 1 ⁺ to 4 ⁺ ) were recorded within 5 days in both experimental and control cultures.

The invention is carried out in the following way:

0.2-20% solution of chitosan with Mm 30000-300000 in 1-5% acetic or succinic acid, containing 15 wt.% Biologically active substances, 15 wt.% Antitumor drug, 0.05-7 wt.% Antibiotic applied in 1-3 doses on a polyamide (PA) yarn of linear density 10-500 tex at a speed of 5-100 m / min, followed by heat-setting of the coating at a temperature of 125-250 ° C.

The invention is illustrated by the following examples:

Example 1

220 g of chitosan Mm 250,000 and 100 g of doxycycline are dissolved in 680 g of 2% acetic acid. The resulting modifying composition is treated with a polyamide twisted yarn with a thickness of 500 tex. Then it is dried at a temperature of 180 ± 5 ° C.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 73.00 Chitosan (HZ) 20.00 Doxycycline (DC) 7.00

The properties of the obtained yarn are shown in table 1.

Example 2

80 g of chitosan Mm 150,000 and 80 g of ciprofloxacin are dissolved in 840 g of 1% acetic acid. The resulting modifying composition is treated with a 150 tex polyamide twisted yarn. Then it is dried at a temperature of 200 ± 5 ° C.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 87.10 Chitosan (HZ) 7.60 Doxycycline (DC) 5.30

The properties of the obtained yarn are shown in table 1.

Example 3

Analogously to example 1, a surgical suture is obtained by treating a twisted thread with a tex thickness of 60 tex with a modifying composition obtained by dissolving 989 g of 1% succinic acid, 10 g of chitosan Mm 50,000 and 1 g of doxycycline.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 99.75 Chitosan (HZ) 0.20 Doxycycline (DC) 0.05

The properties of the obtained yarn are shown in table 1.

Example 4

Analogously to example 1, a surgical suture is obtained by treating a PA braided suture with a thickness of 150 tex with a modifying composition obtained by dissolving in 800 g of 1% acetic acid 100 g of chitosan Mm 50,000 and 100 g of ciprofloxacin.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 84.90 Chitosan 8.10 Ciprofloxacin 7.00

The properties of the obtained yarn are shown in table 1.

Example 5

Analogously to example 1, a surgical thread is obtained by treating PA twisted thread with a thickness of 200 tex with a modifying composition obtained by dissolving in 650 g of 1% acetic acid 100 g of chitosan Mm 30,000, 100 g of doxycycline and 150 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 70,20 Chitosan 8.10 Doxycycline 7.00 Biologically active substances based on biomass of the aralia family (BAS) 14.7

The properties of the obtained yarn are shown in table 1.

Example 6

Analogously to example 1, a surgical suture is obtained by treating a 300 tex thick braided suture with a modifying composition obtained by dissolving in 799 g of 2% acetic acid 150 g of chitosan, 50 g of doxycycline and 1 g of 1-hydroxyhermatran monohydrate.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 80.65 Chitosan 14.80 Doxycycline 4,50 Monohydrate-1-hydroxyhermatran 0.05

The properties of the obtained yarn are shown in table 1.

Example 7

Analogously to example 1, a surgical suture is obtained by treating a PA braided thread with a thickness of 150 tex with a modifying composition obtained by dissolving in 480 g of 2% acetic acid 220 g of chitosan Mm 150,000, 100 g of ciprofloxacin and 200 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 58.00 Chitosan 20.00 Ciprofloxacin 7.00 Biologically active substance 15.00

The properties of the obtained yarn are shown in table 1.

Example 8

Analogously to example 1, a surgical thread is obtained by treating a 10-tex thick PA braided thread with a modifying composition obtained by dissolving in 988 g of 1% succinic acid 10 g of chitosan Mm 50,000, 1 g of mitomecin and 1 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 99.70 Chitosan 0.20 Mitomycin (MC) 0.05 Monohydrate-1-hydroxygermanran 0.05

The properties of the obtained yarn are shown in table 1.

Example 9

Analogously to example 1, a surgical suture is obtained by treating a PA braided suture with a thickness of 150 tex with a modifying composition obtained by dissolving in 800 g of 1% acetic acid 100 g of chitosan Mm 80,000, 50 g of doxycycline and 50 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 82.90 Chitosan 8.10 Doxycycline 4,50 Biologically active substance 4,50

The properties of the obtained yarn are shown in table 1.

Example 10

Analogously to example 1, a surgical suture is obtained by treating a 10-tex thick braided suture with a modifying composition obtained by dissolving in 976 g of 3% acetic acid 10 g of chitosan Mm 200000, 8 g of fluorouracil, 5 g of mitomycin and 1 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 98.95 Chitosan 0.20 Fluorouracil (FU) 0.40 Mitomycin 0.40 Biologically active substance 0.05

The properties of the obtained yarn are shown in table 1.

Example 11

Analogously to example 1, a surgical thread is obtained by treating a twisted thread with a tex thickness of 60 tex with a modifying composition obtained by dissolving in 560 g of 2% acetic acid 220 g of chitosan Mm 50,000, 70 g of fluorouracil, 50 g of mitomycin and 100 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 60.90 Chitosan 20.00 Fluorouracil 5.00 Mitomycin 4.30 Biologically active substance 9.80

The properties of the obtained yarn are shown in table 1.

Example 12

Analogously to example 1, a surgical thread is obtained by treating PA twisted thread with a thickness of 500 tex with a modifying composition obtained by dissolving in 879 g of 5% acetic acid 50 g of chitosan Mm 300,000, 20 g of cyclophosphamide, 1 g of doxycycline and 50 g of 1-hydroxyhermatran monohydrate.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 90.15 Chitosan 4.20 Cyclophosphamide (CF) 1.10 Doxycycline 0.05 Monohydrate-1-hydroxyhermatran 4,50

The properties of the obtained yarn are shown in table 1.

Example 13

Analogously to example 1, a surgical thread is obtained by treating a 150 tex thick PA braided thread with a modifying composition obtained by dissolving in 700 g of 1% acetic acid 100 g of chitosan Mm 150,000, 70 g of cyclophosphamide, 100 g of ciprofloxacin and 30 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 77.45 Chitosan 9.30 Cyclophosphamide 5.30 Ciprofloxacin 7.00 Biologically active substance 0.95

The properties of the obtained yarn are shown in table 1.

Example 14

Analogously to example 1, a surgical suture is obtained by treating a twisted yarn with a thickness of 300 tex with a PA modifying composition obtained by dissolving in 568.5 g of 5% succinic acid 220 g of chitosan Mm 30000, 200 g of cyclophosphamide, 1.5 g of ciprofloxacin and 10 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 64.45 Chitosan 20.00 Cyclophosphamide 15.00 Ciprofloxacin 0.05 Biologically active substance 0.50

The properties of the obtained yarn are shown in table 1.

Example 15

Analogously to example 1, a surgical suture is obtained by treating a PA braided suture with a thickness of 300 tex with a modifying composition obtained by dissolving in 640 g of 1% acetic acid 150 g of chitosan Mm 150,000, 70 g of sarcolysin, 100 g of doxycycline and 40 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 69.90 Chitosan 14.20 Sarcolysin (SZ) 5.10 Doxycycline 7.00 Biologically active substance 3.80

The properties of the obtained yarn are shown in table 1.

Example 16

Analogously to example 1, a surgical suture is obtained by treating a PA braided suture with a thickness of 500 tex with a modifying composition obtained by dissolving in 568.5 g of 1% acetic acid 80 g of chitosan Mm 150,000, 200 g of sarcolysin, 1.5 g of mitomycin, 150 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 62.55 Chitosan 7.60 Mitomycin 0.05 Sarcolysin 15.00 Monohydrate-1-hydroxyhermatran 14.80

The properties of the obtained yarn are shown in table 1.

Example 17

Analogously to example 1, a surgical thread is obtained by treating PA twisted thread with a thickness of 150 tex with a modifying composition obtained by dissolving in 290 g of 1% succinic acid 210 g of chitosan Mm 50,000, 200 g of cyclophosphamide, 100 g of doxycycline, 200 g of biologically active substances.

Receive a surgical thread having the following composition, wt.%

Polyamide thread 43.00 Chitosan 20.00 Cyclophosphamide 15.00 Doxycycline 7.00 Biologically active substance 15.00

The properties of the obtained yarn are shown in table 1.

Example 18

Analogously to example 1, a surgical suture is obtained by treating a 10-tex thick PA braided thread with a modifying composition obtained by dissolving in 987 g of 1% acetic acid 10 g of chitosan Mm 80,000, 1 g of fluorouracil, 1 g of cyclofloxacin, 1 g of biologically active substances.

Get a surgical thread having the following composition, wt.%:

Polyamide thread 99.65 Chitosan 0.20 Fluorouracil 0.05 Ciprofloxacin 0.05 Biologically active substance 0.05

The properties of the obtained yarn are shown in table 1.

Example 19 (prototype)

An antimicrobial suture surgical suture is obtained by treating 360 tex polyamide twisted suture with an alcohol copolyamide solution containing 1 g of copolyamide, 1 g of doxycycline and 5 g of 1-hydroxyhermatran monohydrate in 993 g of ethyl alcohol. The thread is dried at a temperature of 200 ± 5 ° C.

Get antimicrobial suture surgical suture, having the following composition, wt.%:

Polyamide thread 99.44 Copolyamide 0.50 Doxycycline 0.05 Monohydrate-1-hydroxyhermatran 0.01

The properties of the obtained yarn are shown in table 1.

As can be seen from table 1, the proposed suture surgical material has a combined effect. The use of chitosan filaments with active groups as a shell contributes to a more solid fixation of drugs in the shell. Unlike the prototype, chitosan is a natural cationic polyelectrolyte. Each macromolecule unit contains one free active —NH ₂ group and two hydroxyl groups. This makes it possible to more firmly fix in its structure not only medications and enhance their effect, but also allows you to get firmly colored suture threads. The latter fact makes the developed thread visible (distinguishable) in the area of surgical intervention, filled with blood and wound.

During the operation of the suture thread according to the prototype, on the first day 90-95% of the medicinal product introduced into it (“shock dose”) is released, then 4-9% of the drug (“therapeutic dose”) is allocated within 2-4 days, the remaining amount (~ 1%) of the drug (“maintenance dose”) is dosed into the working area for 5-6 days. The total time of prolonged action of the drug is 10-11 days.

In the present invention, on the first day, 45-70% of the administered drug is released from the thread, then 43-20% of the drug is released within 3-4 days, i.e. the exposure time of the “loading dose” increases from 1 to 4-5 days, then 10-11% of the drug is released within 5-6 days (“therapeutic dose”). The remaining amount of the drug (~ 1-1.5%) is dosed into the working area for 6-10 days. The total time of prolonged action of the drug is 16-20 days. Moreover, the manifestation time of the “shock” and “therapeutic” doses in the working area for the prototype thread is 5 days, and for the claimed 10-11 days.

The presence of a large number of active groups in chitosan reveals the possibility of the formation of complexes or other types of compounds not only with drugs, but also with monohydrate-1-hydroxyhermatran and compounds contained in biologically active substances. ("Germatranol" TU 6-02-1-805-94,). Therefore, monohydrate-1-hydroxyhermatran can be introduced into chitosan in its pure form and exhibit its own biological properties during operation. Moreover, thanks to chitosan, the bioactive properties are enhanced and manifest for a longer time.

Suture surgical material containing chitosan and an antibiotic has a greater actimicrobial activity and a longer duration of its manifestation compared to the prototype. Due to its own wound healing properties, chitosan also activates cell proliferation processes.

In addition, given the ability of chitosan to biodegrad, induce apoptosis (programmed death) of cancer cells, an antitumor effect is also possible during exploitation of this suture material in vivo at later stages of the wound healing process.

An additional introduction to the suture surgical material of biologically active substances or monohydrate-1-hydroxyhermatran will enhance the above properties and reduce the toxicity of the drugs used.

The presence of substances such as flavonoids, phytosterols, folic acid, etc., which have an in vivo antitumor effect during operation, will enhance the similar properties exhibited by chitosan.

A surgical suture thread containing chitosan, an antibiotic, a biologically active substance or a monohydrate-1-hydroxyhermatran and an antitumor preparation provides the manifestation of multifunctionality of the thread from the moment of operation: antimicrobial activity, antitumor activity, stimulation of cell proliferation from the moment of use due to the administered drugs; an increase in the duration of the manifestation of the bioactive properties of the drugs introduced; the manifestation at later stages of in vivo operation of the antitumor properties of chitosan itself and the components of biologically active substances and the stimulation of epithelialization processes. The simultaneous introduction of the above components into the yarn leads to a synergistic effect of the manifestation of bioactive properties inherent in each component.

It is possible to use only one function of biologically active suture surgical material - as a donor of drugs of local behavior, injected directly into the affected area during surgery or in another way.

The proposed surgical suture material has the best handling properties, it is softer to the touch, it fits better into the surgical unit.

Claims (3)

1. Suture surgical material, including the thread, consisting of a core of twisted polyamide or braided thread with a sheath with the addition of a medicinal product, characterized in that the sheath consists of chitosan with mol. wt. 30000-300000, and as a medicine use an antibiotic in the following ratio of components, wt.%: Polyamide thread 73.0-99.75 Chitosan pier. wt. 30000-300000 0.2-20.0 Antibiotic 0.05-7.0 2. Suture surgical material, including a thread consisting of a core of twisted polyamide or braided thread with a sheath with the addition of drugs, characterized in that the sheath consists of chitosan, and antibiotics and biologically active substances based on plant biomass are used as drugs aralic or monohydrate-1-hydroxyhermatran in the following ratio, wt.%: Polyamide thread 58.0-99.7 Chitosan 0.2-20.0 Antibiotic 0.05-7.0 Biologically active substances based on plant biomass Aralian family or monohydrate-1-hydroxyhermatran 0.05-15.0 3. Suture surgical material, including a thread consisting of a core of twisted polyamide or braided thread with a sheath with additives of drugs, characterized in that the sheath consists of chitosan, and antibiotics, biologically active substances based on plant biomass, are used as drugs aralic or monohydrate-1-hydroxyhermatran and an antitumor drug in the following ratio of components, wt.%: Polyamide thread 43.0-99.65 Chitosan 0.2-20.0 Antibiotic 0.05-7.0 Biologically active substances based on plant biomass Aralian family or monohydrate-1-hydroxyhermatran 0.05-15.0 Anticancer drug 0.05-15.0