RU115663U1 - BIODEGRADABLE SEAMED SURGICAL COATED SURGERY - Google Patents

Abstract

Surgical suture comprising a polyamide suture with a film-coated biodegradable polymer with drug additives, characterized in that the suture is a core of polyamide twisted or braided suture, and the film coating is a sheath of a biodegradable polymer, which is polylactic acid containing a drug - furagin, with the following ratio of components, wt%:! Polyamide thread 62.23-99.60 Polylactic acid 0.20-30.52 Furagin 0.20-7.25

Description

The invention relates to the field of medicine, in particular, to surgical filaments based on synthetic polymers used as suture surgical material and capable of accelerated decomposition in the human body.

Surgical threads, when used in medical practice, must satisfy the following basic requirements:

- high mechanical properties and high strength;

- a special coating of the thread can eliminate capillarity and wickness;

- reliability of the surgical unit;

- flexibility, elasticity, compactness and good handling characteristics, providing ease of use;

- atraumatic when passing through tissue;

- minimal tissue response, biocompatibility;

- not have an irritating, allergenic and general toxic effect on the body;

- withstand sterilization;

- be compact, the ends of the threads should not become loose.

Of particular note is the need to decompose over time in the body into products that do not cause toxic or teratogenic effects.

One of the ways to impart the necessary properties to suture surgical sutures is by coating them with a polymer membrane, which, in addition to the function of improving the consumer qualities of the surgical suture, can accelerate the processes of its decomposition in the body. At the same time, synthetic threads can also have special bioactive properties, for example, antimicrobial action due to the introduction of antibiotics into their structure, which reduce the treatment time and reduce the frequency of purulent-inflammatory complications.

Known surgical suture thread, consisting of a multifilament core and oriented sheath (application EP 1074270, A61L 17/14, publ. 02/07/2001). The disadvantage of this thread is the lack of drugs in the membrane, which can contribute to the development of secondary infections, inflammations of infected wounds and, as a result, worsen the healing process.

It is also known multicomponent biodegradable fiber, which is a bicomponent fiber, molded by melt technology using special types of dies (RF Patent 2174167, D01F8 / 14, D04H1 / 42, A61L15 / 00, publ. September 27, 2001). In the process of molding, the core-shell threads are immediately formed. However, to obtain such a biodegradable fiber, 2 components are used, which differ from each other in the monomer ratio and, as a consequence, in different melting points. The result is fiber with a high internal ability to crimp and shrink. Therefore, they are not able to be processed into surgical sutures of the required quality. And although the authors of this patent make a reference to the use of multicomponent biodegradable fiber in "living" organisms, only products in the form of non-woven materials are considered.

As a prototype, the authors chose a surgical thread used as a suture surgical material, the method of preparation of which is described in RF patent 2267332, A61L 17/00, A61L 17/06, publ. January 10, 2006. This surgical thread is a polyamide film-coated thread based on a copolymer of ε - caprolactam and hexamethylene diammonium adipate with the addition of drugs - doxycycline and biologically active substances based on biomass of plants of the aralia family. The biomass of plants of the Araliaceae family is grown in special fermenters from ginseng culture cells. The main active substance in the biomass are aminoglycosides, water-soluble polysaccharides, flavanoids and folic acid (in the case of Canadian selection). To obtain this filament, a copolymer based on a copolymer of ε-caprolactam and hexamethylene diammonium adipate is obtained by melt technology, then low molecular weight compounds having a toxic effect are removed from it and dried. Then a polymer solution in ethanol is prepared and in two stages drugs are introduced into it - an antibiotic and a biomass extract in ethanol. Since biomass does not dissolve in this solvent, the active substances are extracted from it by extraction with ethyl alcohol. Then this extract is introduced into a copolyamide solution containing doxycycline, and a polyamide thread is processed with the obtained modifying composition, which, after processing, contains a film on the surface. The main disadvantage of this thread is the long period of its decay in the body. The coating applied to the surface of the thread does not activate the process of decomposition of the thread in the body under the conditions of the formation of poorly defective scar wound tissue. In addition, the process of obtaining it is extremely complex, multi-stage, time-consuming and economically unprofitable. It is enough to note that the minimum growth period of full biomass is at least 1-2 months, which then must (after certain preparatory operations) undergo an extraction process to isolate active substances

The technical task of the present invention is the creation of a surgical suture of combined action, which has a multidisciplinary effect on the pathogenic microflora and activates the decomposition of the surgical suture itself.

The problem in the utility model is solved due to the fact that the surgical thread, including a polyamide filament with a film coating based on a biodegradable polymer, is a core of twisted or braided polyamide filament, and the film coating is a shell of a biodegradable polymer, which is a polylactic acid containing medicinal the drug is furagin, in the following ratio of components, wt.%:

Polyamide thread 62.50-99.60 Polylactic acid 0.20-30.52 Furagin 0.20-7.25

The proposed surgical thread allows you to solve the problem.

The sheath in the surgical thread performs a multidisciplinary function:

1) Allows you to get a compact thread with a smooth atraumatic surface, prevents razvolnenie ends of the thread.

2) Accelerates the process of decomposition of the surgical thread in the body.

3) It is the carrier and donor of a drug that has an overwhelming effect on staphylococci, streptococci and other types of pathogens, including anaerobic infection.

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

Furagin, used as an antimicrobial drug, allows you to get a thread with a long maximum release of the drug and a large bactericidal effect and antimicrobial effect. (M.D. Mashkovsky, Medicines, M., 2002, v.2, p. 304) Furagin belongs to the PharmGroup of antimicrobial derivatives of nitrofuran. International nonproprietary name: Furazidine (potassium salt of furagin - solafur). Synonyms: Furagin soluble, Furagin-standard, Furamag. Composition: active substance: Furazidine: N- {β- (5'-nitro-2'-furyl) -acrylidene} -1-aminogindantoin, melting point Tm. -260 ° C, molecular weight - 264.20.

The synthesis of furan series medical preparations is carried out using furfural and its derivatives as a raw material.

They are not antibiotics and differ from true antibiotics in their mechanisms of action on microbes, as well as in their effectiveness and overall effect on the human body. 5-Nitrofuran compounds - crystalline compounds having a color from light yellow to dark red or brown. All nitrofuran preparations, as a rule, are poorly soluble in water, and good in dimethyl sulfoxide and dimethylformamide. They also differ in thermal stability.

It is very important that the resistance of microbes to nitrofurans develops slowly and does not reach a high degree. The antimicrobial activity of nitrofurans is manifested both in relation to gram-positive (streptococci, staphylococcus), gram-negative bacteria (Escherichia, salmonella, Shigella, Proteus, Klebsiella, Enterobacter) and protozoa (Giardia), and Bartonella, Coccidium, histospomon, histospomon, histospomon fungal infection and a number of large viruses. Under anaerobic conditions, nitrofurans inhibit the acetylation of coenzyme A, without which it is impossible to incorporate pyruvic acid into the tricarboxylic cycle, as a result of which formation of citric acid from oxalic and acetic acid is disrupted. Furagin also selectively acts on pork and bovine types of brucella, inhibiting the growth of most strains at a concentration of 5-20 μg / ml.

Furagin is an original broad-spectrum antibacterial drug; its solubility in water is 4 mg / L. It belongs to heat-resistant antibacterial drugs, withstands exposure to high temperatures without decomposition and change in functional properties. Being not an antibiotic, it has fewer undesirable effects, has less side effects. It also has a bacteriostatic effect on the genitourinary system, since it is excreted in the urine.

Polyamide twisted thread (TU 6-13-00209556-167-2002) or polyamide braided thread (TU 9398-001-93420730-2006) with a linear density of 15-360 tex are used for surgical suture.

For biodegradable casing, polylactic acid (PMA) is used, which is obtained in a batch or continuous process from lactic acid or lactide. It is applied to the thread from the melt at a temperature of 160 ° C. The shell contains a drug: furagin.

Furagin is a broad-spectrum antibacterial drug (F. p. 42-1308-83).

The content of polylactic acid in the biodegradable shell of the surgical thread is from 0.20-30.52 wt.%. With a higher polymer content in the sheath, the thread becomes very stiff and injures the edges of the wound. In addition, the process of cooling the filament with the molten PMC deposited on it is complicated. The lower content of PMC in the shell will not allow to achieve the necessary compactness of the thread.

The content of furagin in the shell is 0.20-7.25. For the manifestation of the antimicrobial action of surgical sutures, a content of 0.20 wt.% Is sufficient. A smaller amount does not provide the necessary therapeutic effect. The increase in the content of furagin in the thread above 7.25 mass% is not advisable, because with an increase in its content, there is no further increase in biological activity and the economic efficiency of using the thread decreases.

Surgical thread is obtained as follows.

Powdered furagin in the required amount is introduced into polylactic acid in the form of granulate by spraying. Then, the obtained modifying mixture is introduced into the melting device, melts at a temperature of 160 ° C and is applied as a melt to the thread, sent to the pre-cooling chamber, passes through a gauge corresponding to a certain diameter of the surgical material and sent to the cooling chamber, where the final cooling takes place threads. The threads are cooled by an air stream.

The obtained threads are determined by physico-mechanical parameters (breaking load, elongation), antimicrobial activity and other biomedical properties, which are presented in tables 1 and 2. These tables show the main medical-technical and biomedical properties of the threads.

The antimicrobial activity of the strand is determined by the method of agar plates for in vitro research of the growth retardation radius of the Bacillus Subtilis L-12 test culture (Bac / Sub /) (Handbook of Microbiological and Virological Research Methods, edited by Birberg N.O., M., Medizdat, 1982).

The biodegradation rate is determined by the loss of the strength characteristics of the filaments as a percentage of the initial strength after keeping it at elevated temperatures of 65, 75, 85 ° C in a medium of 0.025 M aqueous solution of sodium phosphate monosubstituted NaH ₂ PO ₄ (pH = 7.4).

To do this, the samples are placed in flasks with 100 ml of buffer solution and installed in thermostats with the temperatures set in them. 0.2 g of sodium azide (NaN ₃ ) is added to the phosphate buffer solution to inhibit the growth of microorganisms and prevent their contribution to the destruction.

To measure the strength characteristics, the samples are removed from the buffer solution, washed with distilled water and then dried for 4 hours at 40 ° C.

The number of test samples for each temperature is at least 10 pcs. Samples during the test are carried out at least 5 times, the frequency of removal:

- at T = 65 ° C every 5 days;

- at T = 75 ° C every 4 days;

- at T = 85 ° C every 3 days;

The number of samples taken in one take is determined as follows: from 3-5 samples, cut lengths of 30 mm are cut, 7 samples of filaments are randomly selected from these segments. The change in the strength characteristics of the thread is estimated by the change in the strength of its constituent filaments in this way: segments of 30 mm length are cut from 5 samples and used to determine the strength characteristics.

The value of the strength characteristics in the initial state and after each removal is taken equal to the arithmetic mean value of the corresponding series of tests.

The number of animals with signs of a complicated course of the wound process is determined visually. In each series, 18 animals are used (table 1).

The invention is illustrated by the following examples.

Example 1

Faragin is added to polylactic acid (PMA) in an amount of 10% of its mass. The resulting mixture at a temperature of 180 ° C is processed polyamide braided thread with a thickness of 15 tex, then cooled by air flow.

It turns out a surgical thread having the following composition, mass%:

Polyamide thread 89.00 Polylactic acid 10.00 Furagin 1.00

The properties of the obtained yarn are shown in tables 1 and 2.

Example 2

Analogously to example 1, a surgical thread is obtained, a polyamide twisted thread with a thickness of 360 tex is processed with a polylactic acid melt containing 20% furagin.

It turns out a surgical thread having the following composition, wt.%:

Polyamide thread 62.23 Polylactic acid 30.52 Furagin 7.25

The properties of the obtained yarn are shown in tables 1 and 2.

Example 3

Analogously to example 1, a surgical thread is obtained, a polyamide braided thread with a thickness of 90 tex is processed with a polylactic acid melt containing 15% furagin.

It turns out a surgical thread having the following composition, mass%:

Polyamide thread 82.75 Polylactic acid 3 p.m. Furagin 2.25

The properties of the obtained yarn are shown in tables 1 and 2.

Example 4

Analogously to example 1, a surgical thread is obtained, a polyamide twisted thread with a thickness of 220 tex is processed with a polylactic acid melt containing 10% furagin.

It turns out a surgical thread having the following composition, wt.%:

Polyamide thread 99.60 Polylactic acid 0.20 Furagin 0.20

The properties of the obtained yarn are shown in tables 1 and 2.

Example 5

Analogously to example 1, a surgical thread is obtained, a polyamide twisted thread 360 tex thick is processed with a polylactic acid melt containing 15.5% furagin.

It turns out a surgical thread having the following composition, wt.%:

Polyamide thread 70.25 Polylactic acid 25.80 Furagin 3.95

The properties of the obtained yarn are shown in tables 1 and 2.

Example 6 (prototype).

A solution of ε-caprolactam and hexamethylene diammonium adipate copolyamide in ethyl alcohol containing 50 g of copolyamide, 50 g of panaxel and 100 g of doxycycline in 800 g of ethanol is applied to a 90 tex polyamide yarn in a continuous machine and then dried at a temperature of 150 ° C.

It turns out a surgical thread having the following composition, mass%:

Polyamide thread 67.10 Copolyamide 15.50 Panaxel 10.15 Doxycycline 7.25

An antimicrobial surgical suture is obtained by treating a finished composite thread 90 tex thick, passing it through an antimicrobial composition containing 5.0 mass% copolyamide, 5.0 mass% doxycycline, 10 mass% panaxel. Excess solution is removed on the pinch rollers and the thread is sent to the first heat chamber to partially remove the solvent, and then to the second heat chamber to finally remove the solvent. Drying temperature in the first heat chamber is 70 ± 5 ° С, in the second 140 ± 5 ° С.

The properties of the obtained yarn are shown in tables 1 and 2.

As can be seen from table 1, the introduction of furagin into the thread allows you to get a surgical thread with antimicrobial properties and the ability to accelerate the decomposition of surgical polyamide threads, which allows them to be classified as biodegradable suture materials. Moreover, the modifying composition has a positive effect on tissue regeneration and improves the course of the epithelialization process.

The results of assessing the loss of strength of the threads after keeping them in model buffer mixtures that mimic the behavior of the intended application process, fixes a clear directed effect of the film coating of a biodegradable polymer-polylactic acid on the stability of the threads in the body. With an increase in the content in the inventive filament of polylactic acid, the rate of destruction (decomposition of the filaments) increases sharply. So, for example, after 45 days, the thread, depending on the composition of the thread, loses from 8 to 50% of its original strength, while the thread of the prototype only 2%. Moreover, in the first 15 days it retains its properties unchanged. But it is precisely at this time that fibrous tissue forms in the presence of a foreign body in the wound tissue. Standard polyamide thread (kapron) is completely decomposed in the body within 1-1.5 years.

Histological studies of wound surfaces (table 2) show that when using the inventive surgical suture, the size of the fossa and hypertrophic epithelium (scar) already in the early stages of healing (after 3 days) significantly differ from those for the prototype suture. The length, thickness of the scar and the depth of the fossa is significantly less than that of the prototype. The same picture is observed at later stages of healing. A particularly sharp difference is observed in the width of the scar and the thickness of the hypertrophied epithelium. Apparently, this is the influence of the processes of decomposition of the structural element in the wound - a surgical thread that fastens the edges of the wound. In the case of using the inventive thread in these processes, the size of the foreign body (thread) in the wound tissue decreases, which positively affects the course of the wound process and the formation of a full-fledged low-defective scar tissue.

Thus, the obtained results of cytological and histological studies indicate a significant advantage of using surgical filament - polylactic acid as a polymer for film coating in comparison with the prototype.

The introduction of furagin into the surgical thread gives the thread the ability to suppress the infection provoked by most gram-positive and gram-negative microorganisms, including those resistant to other antibiotics, as evidenced by the number of animals with signs of a complicated course of the wound process. Moreover, the inventive thread is characterized not only by a smaller number of wound process complicated by signs of purulent-inflammatory reactions, but also by the total number of wound processes complicated in comparison with the prototype. Apparently, the effect of such a property of furagin as a lesser addiction to the antibacterial drug and the preservation of sensitivity to it also affects.

In addition, the inventive thread has an increased breaking load and less elongation, which makes it more convenient to use and improves handling properties. The use of a biodegradable polymer-polylactic acid as a filament makes the filament more elastic and less traumatic and greatly simplifies the process of using a surgical filament.

The inventive surgical thread is obtained in a simpler one-stage method compared to the multi-stage method of the prototype, which significantly reduces its cost. In addition, the lack of solvent makes the production process of the inventive yarn more environmentally friendly.

Basic medical-technical and biomedical properties of threads Table 1 Prim er Thick thread tex Physical and mechanical properties Modifying mixture,% The content in the thread,% Antimicrobial activity, mm Vas. Sub. The loss of strength of the threads after aging in a buffer solution at different temperatures,% of the initial strength The number of animals with signs of a complicated course of the wound process Breaking load, kgf / gs / tex Elongation,% Poly lactic acid Furagin Polylactic acid Furagin 65 ° C 75 ° C 85 ° C Pyoinflammatory Other Total 15 days 30 days 45 days 15 days 30 days 45 days 15 days 30 days 45 days one 2 3 four 5 7 8 9 10 eleven 12 13 fourteen fifteen 16 17 eighteen 19 twenty 21 22 one fifteen 0.93 69.90 16.6 90.0 10.0 10.0 1.00 28 10.2 14.2 18.6 12.1 15.1 20.0 10.1 18.1 20.7 one one 2 2 360 19.16 53.22 34.3 80.0 20.0 30.52 7.25 42 10.2 18.0 35.0 20.0 28.0 38.0 20.1 30.2 50.2 0 0 0 3 90 4.84 53.83 20.4 85.0 15.0 15.0 2.25 34 12.4 10.1 18.1 14.1 17.1 21.1 15.1 26.1 28.0 0 one one four 220 10.73 48.75 25.4 90.0 10.0 0.2 0.2 5 2.4 3.8 6.2 2.4 4.0 7.1 3.4 4.5 8.2 one one one 5 360 19.16 53.22 34.3 84.5 15.5 25.8 3.95 38 10.0 16.7 30.2 17.1 22.1 36.3 15.5 30.3 40.6 0 0 0 6 about that type 39 1.18 30.5 42.1 Copolyamide - 5.0 Doxycycline-5.0, Pana xel 10.0 Copolyamide - 15.50 Doxycycine - 10.15, Panaxel - 7.25 34 2.1 one one 2

table 2 The size and quality of various structures of the healing wound area after 3/5/7 days Example The size of the pit, microns Dimensions of hypertrophied epithelium, microns The width of the scar, microns The number of derivatives of the skin in p / s Depth Width At the bottom On the surface of the damage in the thicker On the surface thickness length thickness length one 190.1 190.2 350.8 69.4 124.1 58.8 392.4 44.5 68 no or no or 70.1 400.8 60.4 280.3 22.2 12 110.6 16159 - - 87.7 350.4 19 11.0 - - 2 130.0 79.7 131.2 59.3 121.6 61.0 350.6 29.4 9.94 no or no or 66.4 119.0 63.2 395.9 09/20 15.86 105.1 107.7 - - 73.44 345.33 11.8 16.78 - - 3 146.5 131.5 146.3 78.33 114.3 71.8 450.2 31.7 8.71 no or no or 66.1 131.25 66.1 131.25 22.0 13.02 76.8 82.6 - - 71.1 300.8 13.77 15.1 - - four 200.0 105.4 191.4 86.24 16.5 75.4 505.3 39.8 6.45 no or no or 87.1 184.15 75.9 239.4 26.2 8.5 129.1 105.4 - - 75.01 369.8 16.2 10.5 - - 5 144.5 90.4 | 132.2 74.2 127.5 62.0 382.4 31.5 9.14 no or no or 87.1 127.5 63.3 413.5 22.3 13.86 100,4 110.7 - - 73.55 356.4 12.8 15.84 - 6 176 99.5 176.3 78.33 124.3 71.8 460.2 35.7 8.71 prototype no or 66.1 151.25 66.1 151.25 09/24 13.02 66.8 - - 71.1 317.83 13.77 15.1 - - -

Claims (1)

Surgical thread, including a polyamide filament with a film coating based on a biodegradable polymer with the addition of a drug, characterized in that the filament is a core of twisted or braided polyamide filament, and the film coating is a sheath of a biodegradable polymer representing polylactic acid containing the drug - furagin, in the following ratio of components, wt.%: Polyamide thread 62.23-99.60 Polylactic acid 0.20-30.52 Furagin 0.20-7.25