RU2619257C1 - Method for soft tissues defects treatment in patients with diabetic foot syndrome - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: first, the wound defect surface in the defect bottom and walls area and in hyperkeratosis areas is cleansed. Then, "collost" biomaterial is implanted in the defect bottom and walls tissues to a depth of 0.3-0.5 cm in the form of a gel 15% with a syringe to form channels filled with gel. At that, the angle of needle insertion is set from 15° to 45° to the defect surface at the injection point. After implantation, the surface of the defect and the collagen canals are covered with a wound coating with G-Derm histoequivalent, followed by application of a dressing with an antiseptic solution which is moisturized twice a day.

EFFECT: efficacy and reduction of duration of ulcerative soft tissue defects local treatment for patients with diabetic foot syndrome.

2 cl, 9 dwg, 2 ex

Description

The invention relates to medicine, namely to methods for treating soft tissues in patients with diabetic foot syndrome.

In recent decades, diabetes has become a worldwide noncommunicable pandemic. According to statistics, in 2015 there were 415 million people with a verified diagnosis in the world. Mortality and disability in diabetes are due to the development of late complications. One of the most serious complications of diabetes is diabetic foot syndrome (hereinafter referred to as SDS). It occurs in 25% of patients with diabetes mellitus (1). 85% of cases of the development of a trophic ulcer in diabetes mellitus (hereinafter referred to as diabetes) (VDS) end with organ-bearing surgery in the form of amputation of the limb, provided that the tissue defect that forms with the ulcer and is primarily of chronic nature is not closed. Amputation is not a cure operation. Mortality after amputation of the extremity in diabetes mellitus is in second place after lung cancer operations. Mortality for 12 months after amputation at the hip level is 39%. 5-year survival rate among the remaining - 35%. Among patients with diabetes, after the first amputation, amputations of the second limb are experienced from 6 to 30% of patients within 1-3 years, after 5 years - 28-51%.

The course of the wound process in diabetes is characterized by a long duration, complexity and high cost of treatment, an ambiguous therapeutic prognosis (1). Standard treatment methods for SDS do not always allow healing of a wound defect and prevent amputation, which makes the search for new therapeutic approaches relevant (4.1).

It is known to use negative pressure from minus 90 to minus 120 mm Hg. in the defect zone, at which it was possible to reduce the area and depth of wound defects (1), however, this method is not enough without treating defects with traditional methods, and the method allows only slightly reduce the preparation time of the wound defect for the next stage of surgical treatment.

Studies of cellular and molecular features of reparative processes in soft tissues in individuals with diabetes mellitus are known (2). With long-term and poorly controlled diabetes mellitus, the healing process of wound defects can slow down due to a decrease in the level of local growth factors, as well as due to the presence of late micro- and macrovascular complications. Normally, wound healing is a clear sequence of biological and molecular processes, starting with the migration and proliferation of cells, the rearrangement of the extracellular matrix (ECM), and ending with remodeling of newly formed tissues. Despite the relevance of the problem and sufficiently large clinical experience in resolving it, the molecular mechanisms of soft tissue repair in patients with diabetes mellitus remain insufficiently studied, which prevents the adequate selection and effective use of modern means of local treatment of patients' wounds.

There are known applications of gene and cell technologies for treating SDS using the transfer of VEGF, HIF-1, FGF, PDGF, HGF and other growth factors to stimulate angiogenesis and healing of diabetic ulcers (4). The angiogenic and reparative effects of transplantations of autologous mononuclear cells of bone marrow and peripheral blood, angiogenic progenitor cells, stem mesenchymal bone marrow cells, stromal adipose tissue cells in patients with diabetes mellitus (DM) with critical lower limb ischemia have been established. The results of randomized clinical trials (RCTs) showed the beneficial effects of gene and cell therapy on surrogate indices of ischemia, the severity of pain at rest and the healing of ulcers, but the data on the effect on the frequency of amputations are ambiguous. It is necessary to solve the problem of optimal doses and methods of administration of biological agents, predictors of their effectiveness, and also to determine the safety of treatment in the long term.

Studies are known of the role of peptide growth factors in the repair of trophic ulcers, the use of recombinant growth factors to stimulate the healing of trophic ulcers that are resistant to standard treatment. A therapeutic effect of a number of regulators has been established in RCTs, including epidermal growth factor (EGF) [3], platelet growth factor (PDGF) [4], and fibroblast growth factor 2 (FGF-2) in SDS [5]. These growth factors are capable of stimulating the healing of neuropathic ulcers, provided that they are repeatedly administered and high local concentrations are created. The latter circumstance is explained by the fact that when introduced into the body, peptide growth factors are rapidly destroyed by proteolytic enzymes, and therefore the idea arose of introducing growth factor genes into the genome of cells present in the ulcer or ischemia zone to ensure constant expression and creation of concentrations close to physiological . It has been proposed to use bacterial plasmids, viruses, liposomes, nanoparticles, methylcellulose disks, collagen gels and dressings as “conductors” (vectors) of genes [6].

Despite the positive results obtained in separate studies on the treatment of obliterating diseases of peripheral arteries with angiogenic growth factors, no significant effect of this type of treatment on the frequency of amputations and the dynamics of healing of ulcers has been revealed.

Thus, topical treatment of ulcerative defects in diabetic foot syndrome is important for preserving the limb of the patient and improving his quality of life.

Normally, wound healing is a clear sequence of biological and molecular processes, ranging from cell migration and proliferation, rearrangement of the extracellular matrix, and ending with remodeling of newly formed tissue (2). It has been proven that in patients with SDS, the amount of collagen produced by fibroblasts decreases, which leads to a slowdown and / or impossibility of reducing the wound defect (2, 1). The time “from an ulcer to treatment (adequate closure)” is the most important factor determining the outcome of treatment, since a diabetic ulcer is a potentially dangerous complication for a patient’s life (6).

Known methods of treating autodermoplasty using skin grafts of the patient himself, however, they often do not lead to the desired results, since the integration of skin grafts is only 36.4% (5). In addition, the use of autodermoplasty to close a wound defect creates an additional tissue defect in the patient in the area of the donor wound. If the skin flap does not heal in the area of the recipient wound, the patient will have at least two soft tissue defects, and this worsens the prognosis of treatment.

There is a method of treating soft tissues of trophic ulcers, in which a drug based on subtilisins is introduced - a neurometabolic protector and an antibacterial drug, while the ulcer is cleansed of purulent-necrotic plaque with a 3% hydrogen peroxide solution and a bandage based on Hydrofiber and silver ions is applied to the ulcer surface. After the appearance of granulations, a preparation based on bioplastic collagen material is applied until the ulcer defect is completely healed (RF patent No. 2423118, Method for the treatment of trophic ulcers, IPC A61K 31/194, published on July 10, 2011). The method allows to reduce the time and improve the quality of treatment by achieving a stable therapeutic effect and increasing the duration of remission. The disadvantage of the described method of treatment is the application of the material "kollost" on the surface of the wound, which causes difficulties in its conservation and thereby reducing the effectiveness of the treatment. In addition, when preparing the wound site, hydrogen peroxide is used, which does not allow radical removal of the biofilm from the wound surface and does not provide deep and adequate sanitation. Some bacteria remain in the wound, destroy the implant, which delays the repair time.

A known method of treating neuropathic trophic ulcers in diabetic foot syndrome (RF patent No. 2549459, IPC A61K 31/185, publ. 04/27/2015). In accordance with this method, complex treatment is carried out, including the administration of Octolipen and Sulodexide intravenously, then orally, as well as the administration of Convalis for parasthesia and pain in the calf muscles and feet. At the same time, applications are applied to the area of the ulcer defect of the drug Acerbin until the ulcer-wound defect is cleansed. Then, collagen is implanted into the bottom and walls of the defect with the closure of the wound surface with an antiseptic. Such a complex of therapeutic measures ensures the closure of ulcerative defects without autodermoplasty and reduces the treatment time by 2-3 times due to the synergistic action of the components of the complex treatment. RF patent No. 2549459 is selected as the closest analogue.

The disadvantage of the closest analogue is the application of the material “kollost” on the surface of the wound, lining the bottom and walls of the defect, which causes difficulties in its conservation and thereby reducing the effectiveness of treatment.

The objective of the invention is to expand the arsenal of methods for local treatment of ulcerative defects of the soft tissues of the body of a patient with diabetic foot syndrome, increasing the effectiveness of treatment, reducing treatment time.

The technical result is a deep and instant wound cleansing, applying collagen to a deeply cleaned wound in healthy tissue, eliminating the removal of the implant by wound exudate and its destruction, screening collagen and a defect from exogenous factors, creating conditions for absorbing wound exudate.

The problem is solved and the technical result is achieved by a method of treating soft tissue defects in a patient with diabetic foot syndrome, including the following steps:

- Carry out the cleaning of the surface of the wound defect using one of the methods of mechanical antiseptics: surface curettage, hydrosurgical ultrasonic treatment. This allows you to quickly and adequately prepare the "site" for the subsequent second and third stages, removing devitalized tissue, biofilm in the area of the bottom and walls of the defect, and areas of hyperkeratosis in the area of the edges of the wound;

- Spend the implantation of biomaterial - non-immunogenic native collagen type 1 "kollost" in the form of a gel of 15%. The “collost” biomaterial is made of cattle skin with the removal of the epidermis, adipose tissue and all dermal cells, and with the preservation of the collagen matrix;

- The implantation of the “collost” in the tissue is carried out in several stages deep into the tissues, 0.5-0.3 cm deeper than the bottom and walls of the defect, at the exit of the needle, with the formation of channels filled with biomaterial;

- The angle of introduction of the needle is chosen from 15 ° to 45 ° to the surface of the defect at the puncture point, while the risk of its “washing off” by the wound exudate and destruction in case of re-infection and the formation of a biofilm of the wound defect are mitigated. This stops the state of wound cachexia, insufficiency of the own collagen of the macroorganism in the wound area, stimulates reparative processes, the formation of the body’s own tissue and its remodeling;

- Spend the closure of the surface defect with a wound dressing Ji-Derm. This is a histoequivalent - a bioplastic material obtained on the basis of a structured form of hyaluronic acid and a peptide complex. Using it to close the defect after implantation of the “collost” biomaterial, thereby collagen and the defect itself are screened from exogenous factors, create conditions for the absorption of exudate by providing a moist wound environment;

- After closing the defect, the G-Derm coating will apply the usual dressing with an antiseptic followed by periodic wetting.

It is known to use the histoequivalent material - bioplastic Ji-Derm in general and plastic surgery, aesthetic medicine and cosmetology to increase the efficiency of wound healing, restoration of cell skin layers after cosmetic procedures (RF patent No. 2513838, publ. 04.20.2014, www.g-derm .ru / medicine / bioplastic-material-g-derm). Its effectiveness is determined by the maximum structural similarity with the outer layers of human skin.

It is widely known that collagen is used to relieve the state of wound cachexia, failure of its own collagen in the wound area, stimulation of reparative processes, formation of the body’s own tissue, and its remodeling. This is also evidenced by the information from the above analogues.

However, it is not known that 15% of the collagen gel is injected into the depths of tissues by extrusion to prevent its removal by wound exudate and its destruction, which is ensured by the introduction of collagen to a depth of healthy tissues deeper than the bottom and walls of the defect by 0.3-0.5 cm with the formation of a channel / tunnel system collagen. Also unknown is the angle of incidence of collagen in the tissue within the stated limits to obtain the optimal healing result. The application of the proposed methods for cleansing the wound in combination with the introduction of collagen by syringing into tissues is unknown, which allows you to quickly carry out cleaning of the wound, and introduce collagen, and shield the wound surface.

The method is as follows.

After anesthesia according to one of the generally accepted methods, depending on the condition of the patient, the surface of the wound defect is first cleaned with one of the methods of mechanical antiseptics: surface curettage, hydrosurgical ultrasound treatment. This allows you to adequately prepare the "site" for subsequent stages, removing devitalized tissue, biofilm in the area of the bottom and walls of the defect and sections of hyperkeratosis in the area of the edges of the wound.

Then they carry out the implantation of the “kollost” biomaterial in the form of a 15% gel in the bottom and walls of the defect. For this, the syringe with biomaterial in the official packaging is preheated in a water bath to 36-37 ° C. After that, the packaging is opened in compliance with the rules of asepsis and antiseptics. The introduction of biomaterial is carried out to a depth of tissue deeper than the bottom of the wound and from the walls from 0.3 to 0.5 cm at the exit of the needle. If the biomaterial is introduced deeper, collagen will not reach the surface of the wound. The tissue will form in the depth in the form of a shaft, and epithelialization must be achieved during treatment. If biomaterial is introduced to a depth of less than 0.3 cm, it will all leak out without the formation of channels with collagen. The indicated depth of collagen administration allows creating a channel, a tunnel and filling it with biomaterial when injecting a needle. The needle insertion angle ranges from 15 ° to 45 ° to the surface of the defect. This inclination of the needle provides sewer along, parallel to the wound surface and increases the length of the channel. An angle of less than 15 ° is technically impossible due to the edges of the wound. Thus, the “collost” is introduced into the bottom of the wound, edge, wall, into the entire tissue array. The number of introducing the gel “collost” in one “injection” is from 0.2 to 0.3 ml ³ . For one introduction of the biomaterial, its distribution over the area per 1 cm ^{2 of the} surface of the wound is achieved. The total amount of biomaterial used depends on the number of injections, i.e. area and depth of soft tissue defect.

Next, the defect is closed with J-Derm material. Previously, the material is immersed in sterile saline for 5 minutes. A flap is formed according to the size and contours of the defect. The flap "G-Derm" is laid with a smooth surface on the wound and spread until it is firmly fixed along the relief of the defect with the removal of air bubbles and drops of exudate.

After the defect is closed, the postoperative wound is closed with a bandage with an antiseptic solution (miramistin solution 0.01%, chlorhexidine solution 0.05%). The dressing is moistened 2 times a day. The first control ligation is carried out on the 3rd day. Biodegradation of the material "D-Derm" occurs on the 7-10th day.

Photo 1-9 illustrates the surface condition of the soft tissue defect in patients with diabetic foot syndrome at different stages of treatment; in photo 1-5 - according to example 1, in photo 6-9 - according to example 2.

The following are examples of the implementation of the proposed method of treatment.

Example 1

The patient LB, born in 1940, was admitted to the Center “Diabetic foot” of Kazan with a diagnosis of diabetic foot syndrome (W3) on the left, diabetic neuropathy, diabetic angiopathy of the KHAN of 4 tbsp. KINK. Condition after balloon angioplasty. Reperfusion syndrome. Menkeberg sclerosis. Condition after amputation of 2-3 fingers of the left foot. DPN, a sensorimotor and vegetative form, moderately expressed. DOAP. Type 2 diabetes mellitus, severe, subcompensated.

At the time of receipt of a complaint about a defect in the skin in the left foot, pain; swelling of the tissues of the left foot and lower leg, body temperature up to 37.3 ° C. Before admission, she was treated on an inpatient and outpatient basis for 5 months: mechanical recanalization, balloon angioplasty of the left MBA and PBBA, amputation of 2, 3 toes of the left foot, drug therapy, local therapy. Without success. The defect of the foot tissues tended to increase, pain and edema syndrome increased (see photo 1).

Hydrosurgical ultrasound treatment of the wound surface and implantation of the “collost” biomaterial in the form of a 15% gel were performed (photo 2).

In photo 3, the defect is covered by the G-Derm material after implantation of the Kollost biomaterial.

Photo 4 shows the type of wound on day 18 after implantation of the “collost” material and the application of the “D-derm” material. Epithelization and reparative processes are observed at the sites of the introduction of “collost” both along the edges of the wound defect and in the area of the bottom.

Photo 5 shows the type of wound on the 28th day after implantation of the “collost” material and the application of the “D-derm” material. The defect is epithelized.

Example 2

Patient S.V., born in 1967, was admitted to the Center “Diabetic foot” in Kazan with a diagnosis of diabetic foot syndrome (W2), neuroischemic form. Trophic ulcer of the right foot. KHAN 2A. D.P.N., sensorimotor and vegetative form, moderately expressed. Stop Charcot. Condition after amputation of the fingers of the right foot, necrectomy and autodermoplasty. Treatment is without success. Mechanical necrectomy; implantation of the “collost” material is performed when the patient is on the stomach.

Photo 6 shows the preparation of soft tissues for treatment.

Photo 7 shows the introduction of collagen with a syringe into the depths of defective tissues.

Photo 8 shows the imposition of J-Derm material on the wound.

Photo 9 shows the defect state on the 18th day after implantation of the “collost” biomaterial and application of the “D-Derm” material.

The described treatment regimen in accordance with the invention was applied to 28 patients with neuroischemic ulcers in diabetic foot syndrome. It was possible to close ulcerative defects without resorting to autodermoplasty; the duration of treatment was 5-28 days with a prototype treatment period of up to 36 days, with a treatment period of other known methods described up to 58 days, with questionable (temporary remission) outcomes. After the indicated course of treatment, the course of the disease was significantly facilitated and a stable remission was obtained. Seventeen patients were treated with the proposed method in a day hospital, the period of inpatient treatment of the remaining nine patients was only 5 days, which already indicates the effectiveness of the proposed method of treatment compared with the known ones.

The advantages of the proposed method are the following:

- When preparing a wound site for collagen, methods of chemical antiseptics are not used (hydrogen peroxide 3%, in accordance with one of the analogues). Hydrogen peroxide in the analogue does not allow to radically remove the biofilm from the wound surface and does not provide deep and adequate sanitation. Its use leads to the fact that some bacteria remain in the wound, destroy the implant, and thus the repair time is delayed; the proposed method is free from this drawback;

- The terms of wound cleansing are reduced; when using acerbine in the prototype, the cleaning time is from 5 to 7-10 days, in accordance with the invention in one manipulation. All steps of the method according to the invention are not divided in time and are completed in one surgical operation; this allows you to quickly carry out treatment without worsening the condition of the wound during its rapid cleansing and further accelerate the epithelization of tissues;

- The material "kollost" is not applied to the wound surface, but is injected directly into the tissue with the formation of channels filled with collagen, which allows you to save it in the tissues, to exclude its removal beyond the application site;

- Application of the G-Derm material creates a protective framework for the wound surface, screens defect and collagen, provides a moist environment, creates conditions for the absorption of wound exudate and for reparative processes;

- The duration of treatment is reduced;

- Technically, the treatment method is simplified.

Thus, according to the results of treatment by the proposed method, the following conclusions can be made:

1. Accelerated healing of wound defects in patients with SDS was achieved.

2. In the proposed method, only domestic medical products that have passed the necessary registration are used.

3. The proposed method for the treatment of soft tissue defects in CDS allows you to completely abandon autodermoplasty and causing additional wounds to the patient.

4. The proposed method of treatment is simple in technical execution and can be carried out in ultrashort stationary conditions and in a day hospital.

Literature

1. Zaitseva E.L. The effect of negative pressure therapy on reparative processes in the soft tissues of the lower extremities in patients with neuropathic and neuroischemic forms of diabetic foot syndrome / E.L. Zaitseva, L.P. Doronina, R.V. Molchkov, I.A. Voronkova et al. // Diabetes mellitus. - 2014. - No. 3. - S. 113-121.

2. Zaitseva E.L. The role of growth factors and cytokines in reparative processes in soft tissues in patients with diabetes mellitus / E.L. Zaitseva, A.Yu. Tokmakova // Diabetes mellitus. - 2014. - No. 1. - S. 57-62.

3. Komelyagina E.Yu. The Russian version of the questionnaire for assessing the quality of life of a patient with peripheral polyneuropathy: validation and application prospects / E.Yu. Komelyagina, O.M. Uvarova, M.B. Antsiferov // Diabetes mellitus. - 2014. - No. 2. - S. 56-65.

4. Konenkov V.I. Gene and cellular technologies in the treatment of diabetic foot syndrome / V.I. Konenkov, V.V. Klimontov // Diabetes mellitus. - 2014. - No. 1. - S. 63-69.

5. Izzo V. Department of Internal Medicine. Tor Vergata University, Rome, Italy. Matrix Metalloproteinases levels influence the integration of dermal grafts in diabetic foot ulcers / V. Izzo, M. Meloni, E. Vainieri [et al.] // XII. Meeting of the Diabetic Foot Study Group of the EASD. - Bratislava, Slovakia, 2014 .-- P. 50.

6. Rasmussen Anne Patient and health care provider related delay in the treatment of diabetic foot ulcers / Anne Rasmussen, K. Engelhand, N. Bonnichsen [et al.] // XII Meeting of the Diabetic Foot Study Group of the EASD. - Bratislava, Slovakia, 2014 .-- P. 24.

Claims (2)

1. A method for the treatment of defects in the soft tissues of a patient with diabetic foot syndrome, in which the surface of the wound defect is cleaned in the region of the bottom and walls of the defect and sections of hyperkeratoses, after cleansing in the tissue of the bottom and walls of the defect to a depth of 0.3-0.5 cm, implantation is performed the “kollost” biomaterial in the form of a gel by 15% syringing with the formation of channels filled with gel, while the angle of introduction of the needle is set from 15 ° to 45 ° to the surface of the defect at the puncture point, after implantation, the surface of the defect and the channels are closed lagena wound coating gistoekvivalentom Ji-Derm followed by application of a bandage with antiseptic solution, and its moisture twice a day. 2. The treatment method according to claim 1, characterized in that the surface of the wound defect is cleaned using mechanical antiseptic methods: surface curettage or hydrosurgical ultrasonic treatment.

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