RU2148989C1 - Preparation for treatment of sluggish wound and trophic ulcer (variants) - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: invention relates to treatment of sluggish wounds and trophic ulcers on the background of sensibilization. Method involves application of bandage on wound or ulcer impregnated with xymedone-hydrocortisone-boric acid aqueous solution at the following ratio of components, wt.%: xymedone, 0.8-1.4; hydrocortisone hemisuccinate, 0.09-0.13; boric acid, 1.5-2.5; and distilled water, the balance; or ointment on lanolin-vaseline base at the following ratio of components, wt.%: xymedone, 0.8-1.4; hydrocortisone hemisuccinate, 0.09-0.13; boric acid, 1.5-2.5; anhydrous lanolin, 45.97-47.61; and medicinal vaseline, the balance; or talc-base dusting powder at the following ratio of components, wt.%: xymedone, 0.8-1.4; hydrocortisone hemisuccinate, 0.09-0.13; boric acid, 1.5-2.5; and medicinal talc, the balance. EFFECT: enhanced therapeutic effectiveness, decreased adverse effect of drugs, absence of complications, broadened spectrum of effect. 4 cl, 8 ex

Description

 The invention relates to medicine, in particular to surgery, and can be widely used in the practice of treating non-healing wounds and trophic ulcers, accompanied by the occurrence of eczematous contact dermatitis. The regeneration processes in these patients are sharply inhibited and are accompanied by excruciating itching, pain. We repeatedly reported this in the press (Izmailov G.A. Autodermoplasty in clinical practice. - Kazan, 1980, which is confirmed by literature data (Sashchikova V.G. et al. Vestn. Khir. - 1982, N 4. - p. 71 - 75).

 The treatment of wounds and trophic ulcers is one of the most difficult problems of surgery. The countless variety of various mechanical and physical methods, surgical techniques, as well as pharmacological agents indicate their inefficiency (Wounds and wound infection. Edited by M.I. Kuzin and V.M. Kostyuchenok. - M .: Medicine, 1981).

 The use of hormonal preparations in the form of ointments (flucinar, etc.) for these purposes, although it contributes to the subsidence of dermatitis, but at the same time there is an inhibition of healing processes, the course of regional epithelization is especially delayed. In addition, granulations become loose, easily vulnerable and uneven in relief. Such drugs do not have antiseptic properties, and the suppression of local immunity contributes to the development and spread of infection (V. Struchkov and other Guidelines for purulent surgery. - M.: Medicine, 1984). Therefore, hormonal ointments are not recommended for purulent wounds (Mashkovsky M.D. Medicines. - M.: Medicine, 1997. - Part 1).

 For skin diseases accompanied by pyogenic infection, ointments (Sinalar-N, flucinar) or creams containing antibiotics (along with glucorticosteroids (neomycin, gramicidin, etc.) are used). However, the inclusion of antibiotics increases the risk of developing dangerous complications - allergic reactions in the form of local and general manifestations.

 Due to various contraindications (heart disease, the presence of tumors, etc.) in this group of patients, it is impossible to use physiotherapeutic procedures (ultrasound, UHF, ultraviolet radiation, etc.).

 Long-term treatment, the frequent presence of these patients in the hospital lead to the joining of a hospital multidrug-resistant infection, which is especially difficult to treat - the blue pus stick, which is found in 100% of cases. The stick promotes tissue necrolysis, prevents the formation of epithelium and granulation, as well as the engraftment of a dermatograft.

 The only available effective and cheap anti-Pseudomonas aeruginosa is boric acid, which has a pronounced antimicrobial effect. Boric acid inhibits the growth of blue pus bacillus, promotes the swelling of cell colloids, converting them from a semi-solid to a liquid state, accelerates the rejection of necrotic tissues, cleansing the wound surface (Zhitnyuk I.D. Treatment of wounds with a powder mixture. - Naval doctor. - 1859. - N 2.p. 8).

 However, long-term clinical observations showed that in addition to the positive bacteriostatic effect, boric acid in known concentrations (2 - 5%) has side effects: marked local pain, increased bleeding of tissues; delays the healing process, causing inhibition of the genesis of the epithelium, granulation tissue, and in some cases even the death of its surface layers.

 The known drug is xymedon [N- (B-hydroxyethyl) -4,6-dimethyldihydropyrimidone-2] for topical treatment of non-healing wounds and trophic ulcers (RF patent N 2063752, IPC6, A 61 K 31/505, 1996), taken as a prototype.

 The disadvantage of this drug is that when it is used, the symptoms of eczematous dermatitis, which is a constant companion of non-healing wounds and trophic ulcers, do not disappear.

 The aim of the invention is to increase the therapeutic efficacy of treatment, reduce the side effects of drugs, expand the spectrum of action.

 This goal is achieved by the fact that the proposed new drug with a higher therapeutic effect in the treatment of long-healing wounds and trophic ulcers. The proposed drug has a multivalent effect, aimed at the main sides of the wound healing process, possessing antibacterial, anti-inflammatory, antexudative, anti-allergic and antipruritic activity. In addition, the drug provides a distinct stimulation of the growth of granulations and regional epithelization, which reduces the treatment time for wounds and ulcers.

 The proposed drug contains active substances and a drive. As active components, the product includes xymedon, a new 3rd generation pyrimidine derivative, hydrocortisone hemisuccinate and boric acid.

Xymedon as a chemical compound is known and described in the literature. It is a crystalline powder from white to light pink in color with a boiling point. 137.5 - 139.5 ^o C, soluble in water. Approved by the pharmaceutical committee of the USSR Ministry of Health for use by adults as an anti-burn agent (ed. St. N 1685454, class A 61 K 31/505, publ. 23.10.91), as well as for local treatment of long-healing wounds and trophic ulcers (US Pat. . RF N 2063752, IPC6, A 61 K 31/505, 1996).

 The drug is offered in various dosage forms.

An aqueous solution of xymedono-hydrocortisone-boron in the following ratio of components, wt.%:
Xymedon - 0.8 - 1.4
Hydrocortisone Hemisuccinate - 0.09 - 0.13
Boric acid - 1.5 - 2.5
Distilled Water - Else
Xymedonohydrocortisone boron ointment on a lanolin-vaseline basis in the following ratio of components, wt.%:
Xymedon - 0.8 - 1.4
Hydrocortisone Hemisuccinate - 0.09 - 0.13
Boric acid - 1.5 - 2.5
Anhydrous lanolin - 45.97 - 47.61
Vaseline Medical - Else
Xymedonohydrocortisone boron powder on talc in the following ratio of components, wt.%:
Xymedon - 0.8 - 1.4
Hydrocortisone Hemisuccinate - 0.09 - 0.13
Boric acid - 1.5 - 2.5
Talc Medical - The rest is up to 100%
The preparation is prepared as follows: the components are mixed in the sequence: xymedon, boric acid, water or anhydrous lanolin and medical vaseline or medical talcum powder, the last is added hydrocortisone hemisuccinate, i.e. solution, ointment and powder (all the proposed lexforms) are prepared in accordance with generally accepted pharmacopeia rules.

 The proposed drug in its therapeutic effect on the body is not the sum of the therapeutic actions of the components, but is a new drug with an unexpectedly higher therapeutic effect.

 The drug is used as follows.

 Prescribe a general non-specific sensitizing therapy with the inclusion of antihistamines. The skin near the wound and ulcers are thoroughly washed with a 0.5% aqueous solution of detergent. Then, one basic circular gauze layer is applied to the wound or ulcer and the skin surrounding the defect, on which removable separate gauze napkins with the proposed preparation are laid. If you use the tool in the form of a solution, then wetting is carried out twice a day at intervals of 12 hours with the change of the upper layers of the dressing as they get wet with wound contents. In the absence of spontaneous healing of a wound or ulcer, a skin-plastic surgery is performed with a free graft with preliminary exposure to it in xymedonohydrocortisone-boron solution for 2-3 minutes. Applications of the latter and the application of the ointment are performed on the graft and surrounding skin and in the post-transplant period until the graft is completely engrafted. Such course therapy is repeated in 3 to 4 months. once during the first year after discharge of the patient from the hospital. Daily dressings are performed for 10 to 12 days.

 Treatment with the proposed method using the drug (solution, ointment, powder) in the conditions of the city purulent-septic center was carried out in 38 patients with long-term non-healing wounds and with trophic ulcers of various origins. 95% of patients showed signs of general and local allergies. The observed autosensitization contributed to the aggravation of trophic tissue changes. As a rule, in most cases, the onset of ulcers was preceded by local dermatitis with the occurrence of weeping eczema with desquamation of the epidermis. The exposed epidermis was exposed in the center. As a rule, local stable dermatitis was detected against the background of a general allergic reaction.

 Local manifestations in individuals with torpid flowing wounds and ulcers were characterized by reddening of the skin, atrophic granulations with purulent-fibrinous deposits, edema, and often with a complete absence of signs of epithelization. In bacteriological studies of wound exudate, an increase in microbial associations was detected, the most common were staphylococci and streptococci, as well as Proteus and bacillus of blue-green pus. The microbial factor exacerbated the purulent-necrotic process. The control group consisted of 26 similar patients treated in the traditional way using boric acid and xymedon in the form of ointment and powder.

 Clinical observations of patients treated with the proposed drug showed significant advantages of this drug over traditional ones. We give examples of effective clinical use of the drug for various values of the ingredients of the composition (in wt.%).

Example 1. Patient S., 40 years old, was admitted 10.01.1988 with a long-term non-healing wound of the posterior surface of the right lower leg. The wound was formed after an open fracture of the lower leg bones 1.5 years ago. It was treated stationary, twice failed autodermoplasty with a perforated skin flap. The wound 15x7 cm has a flat bottom with pale granulations. The use of a 10% solution of Xymedon led to some revitalization of granulations, but no noticeable improvement in wound healing was noted. We resorted to the use of xymedonohydrocortisone boron aqueous solution in the recipe, wt.%:
Xymedon - 0.8
Hydrocortisone Hemisuccinate - 0.09
Boric acid - 1.5
Distilled Water - Else
Already on the 3rd day, positive dynamics were noted. Signs of dermatitis gradually began to subside, granulation acquired by the end of the 2nd week. pink color, marginal and islet epithelization appeared. Free autodermoplasty with a mesh flap is made. After discharge for 1 year, 10-12-day courses of anti-relapse treatment were carried out by local applications of the proposed solution at intervals of 3-4 months. Persistent recovery.

Example 2. Patient R.Sh., 62 years old, was admitted on July 11, 1994 with a long-term non-healing scar-trophic ulcer of the lower leg that arose after a severe injury in 1993. A skin-plastic surgery was performed twice, but the ulcer recurred. This was preceded by pronounced persistent eczematous dermatitis. An ulcer 7x7 cm in the lower third of the right lower leg is objectively determined. The skin near the ulcer is hyperemic, macerated, and painful. Complex therapy was prescribed, including local use of the proposed xymedonohydrocortisone boron ointment in the recipe, wt.%:
Xymedon - 0.8
Hydrocortisone Hemisuccinate - 0.09
Boric acid - 1.5
Anhydrous lanolin - 45.97
Vaseline - Else
On the 24th day, the ulcer completely healed, a soft, painless scar formed. After discharge from the hospital, anti-relapse therapy courses were twice conducted with the proposed remedy. A lasting recovery has come.

Example 3. Patient R., 59 years old, was admitted to the surgical clinic on November 1, 1995 with complaints of constant debilitating pain in the left lower leg. The patient considers himself 2.5 years. He notes frequent allergic reactions not only to drugs (antibiotics, etc.), but also to foods (fish). Over 7 years suffering from hypertension. Constantly treating ulcers with the use of various ointments, including Xymedon-based lanolin-vaseline. No therapeutic effect was noted. An ulcer of 5x4 cm with uneven edges, the bottom of which is covered with pathological granulations, is determined on the front surface of the lower leg. The skin near the ulcer is inflamed, there are areas of exfoliated epidermis. Combination therapy was prescribed with the inclusion of xymedonohydrocortisone boron powder in the following recipe, wt.%:
Xymedon - 0.8
Hydrocortisone Hemisuccinate - 0.09
Boric acid - 1.5
Talc - Rest
Example 4. Patient Z., 60 years old, was admitted to the clinic on February 16, 1997 with a diagnosis of vasotrophic ulcer of the left leg. The duration of the disease is more than 20 years. She was treated on an inpatient and outpatient basis. In 1992, an operation was performed - left saphenectomy for varicose veins. In the complex of conservative therapy used xymedonohydrocortisone boron solution in the following ratio of components, wt.%:
Xymedon - 1.4
Hydrocortisone Hemisuccinate - 0.13
Boric acid - 2.5
Distilled Water - Else
March 3, 1997 the patient was discharged home with a healed ulcer.

Example 5. Patient L., 44 years old, was admitted to the purulent-septic surgery department on September 1, 1998 with an extensive long-term non-healing wound of the right shoulder with severe signs of near-wound dermatitis. First, a solution of xyhydroboron was applied locally, then an ointment was used in the following recipe, wt.%:
Xymedon - 1.4
Hydrocortisone Hemisuccinate - 0.13
Boric acid - 2.5
Anhydrous lanolin - 47.61
Vaseline Medical - Else
There was a complete epithelization of the wound. Recovery. Discharged home September 24, 1998

Example 6. Patient F., 70 years old, was admitted with a long-term non-healing wound of the right foot. Three months ago I received an injury to this foot - I pressed it with a log. About 20 years with diabetes. Upon admission to the hospital on the back of the foot, a wound of 6x10 cm with a purulent-necratic bottom was determined. Under anesthesia, a mechanical necrectomy was performed. Locally used powder "Xyhydroboron", wt.%:
Xymedon - 1.4
Hydrocortisone Hemisuccinate - 0.13
Boric acid - 2.5
Talc Medical - Else
Complete wound healing, was discharged home on the 18th day after hospitalization.

Example 7. Patient F., 53 years old, was admitted on May 10, 1997 with a long-term non-healing wound in the sacral region. A year ago, she received a severe pelvic injury with a broken bone. The bottom of the wound is covered with fibrin, granulation is sluggish. Complex therapy has begun with the inclusion of local ointment applications with "Xyhydroboron" in the recipe, wt.%:
Xymedon - 1.1
Hydrocortisone Hemisuccinate - 0.11
Boric acid - 2.0
Anhydrous lanolin - 46.79
Vaseline Medical - Else
On the 12th day, the wound cleansed of purulent-fibrinous deposits and was covered with bright granulations. Successful autodermoplasty with a dermatome flap was made. Discharged home on June 8, 1997.

Example 8. Patient I., 54 years old. He entered the clinic on February 25, 1996 with Fournier's disease. Exposed penis and scrotum. After a necrectomy, the resulting wound was treated topically with a solution of Xyhydrobor in the prescription, wt.%:
Xymedon - 1.1
Hydrocortisone Hemisuccinate - 0.11
Boric acid - 2.0
Distilled Water - Else
The wound surface was covered with bright, well-supplied granulations. Combined skin plastic made. Discharged with full recovery.

Example 9. Patient V., 32 years old, was admitted to the purulent-septic surgery department on October 17, 1996 with an extensive wound of the anterior thigh and inguinal region. For 3 months he was unsuccessfully treated in one of the city hospitals. Repeatedly performed plastic surgery. Assigned to complex therapy. Topically applied first is an aqueous solution of "Xyhydroboron", and then in the form of powder in the recipe, wt.%:
Xymedon - 1.1
Hydrocortisone Hemisuccinate - 0.11
Boric acid - 2.0
Talc Medical - Else
The wound was significantly reduced in size, covered with granulations. Autodermoplasty. Discharged with recovery
The antibacterial ability of the proposed drug - a solution and other preparative forms was significantly higher (5 times) of the known agent against staphylostreptococci and Escherichia coli.

 As a result of a clinical trial, in all patients of the experimental group, growth of Pseudomonas aeruginosa was suppressed, which was not observed in the control. A change in the nature of microflora was detected already on 3-4 days. from the moment of treatment. The number of colonies decreased, the number of neutrophils decreased.

 Comparative results of the therapeutic efficacy of the known and proposed agents are most expressive in terms of eliminating eczematous dermatitis. The local positive effect in the experimental group was reflected in the rapid (on 2 - 3 days) relief of signs of eczema and dermatitis, reduction of tissue edema, the disappearance of hyperemia, pain and maceration. The elimination of the long-existing painful eczematous dermatitis led to a sharp improvement in the patient’s mental status, normalization of sleep and appetite, and an increase in motor activity.

 An earlier positive dynamics in the experiment was manifested in the cleansing of the wound surface from purulent-fibrinous deposits, in the appearance of healthy granulations and marginal epithelization, in the high adhesion of the dressing. In 9 patients, healing began by epithelialization and the formation of a soft mobile scar. In the control, spontaneous healing was noted in only 3 cases.

 Successful skin-plastic surgeries in the experiment were performed 5–7 days earlier than in the control, which significantly reduced the time for patients to be hospitalized. Relapse of the ulcer occurred in 2 cases in the experimental group, in the control - in 6. It should be noted that the age of the disease arose in the experience in patients who, for various reasons, did not take anti-relapse treatment courses.

 The drug was highly effective at the values of the active components indicated in the table.

 The drug with concentrations less than the lower values of the active components is not very effective, and with concentrations greater than the large values of the active components is not advisable.

 Thus, the use of xymedonohydrocortisone boron preparation in the complex treatment of patients with long-term non-healing wounds and trophic ulcers on the background of general and local allergies leads to a quick relief of allergy symptoms, acceleration of epithelization and the formation of granulations. The proposed drug helps to improve the results of skin plastics, reduces the frequency of relapse of the disease.

 The therapeutic effect of the proposed drug was not obvious and is not, as shown during clinical trials, the sum of the effects of the active components.

 The proposed drug can be recommended for widespread use in surgery, traumatology, combustiology.

Claims (1)

1. A preparation for the treatment of non-healing wounds and trophic ulcers, containing an active principle and a backbone, characterized in that it contains N- (β-hydroxyethyl) -4,6-dimethyl-dihydropyrimidone-2 (xymedon) as an active principle, hydrocortisone hemisuccinate, boric acid, and anhydrous lanolin and petrolatum as a base, with a ratio of components, wt.%:
N- (β-hydroxyethyl) -4,6-dimethyldihydropyrimidone-2 (xymedon) - 0.8 - 1.4
Hydrocortisone hemisuccinate - 0.09 - 0.13
Boric acid - 1.5 - 2.5
Anhydrous lanolin - 45.97 - 47.61
Vaseline - Else
2. A preparation for the treatment of non-healing wounds and trophic ulcers, containing an active principle and a base, characterized in that it contains N- (β-hydroxyethyl) -4,6-dimethyl-dihydropyrimidone-2 (xymedon) as an active principle, hydrocortisone hemisuccinate, boric acid, and as the base, distilled water with a ratio of components, wt. %:
N- (β-hydroxyethyl) -4,6-dimethyl-dihydropyrimidone-2 (xymedon) - 0.8 - 1.4
Hydrocortisone hemisuccinate - 0.09 - 0.13
Boric acid - 1.5 - 2.5
Distilled Water - Else
3. A drug for the treatment of non-healing wounds and trophic ulcers, containing an active principle and a backbone, characterized in that it contains N- (β-hydroxyethyl) -4,6-dimethyl-dihydropyrimidone-2 (xymedon) as an active principle, hydrocortisone hemisuccinate, boric acid, and talc in the ratio of components, wt.%:
N- (β-hydroxyethyl) -4,5-dimethyl-dihydropyrimidone-2 (xymedon) - 0.08 - 1.4
Hydrocortisone Hemisuccinate - 0.09 - 0.13
Boric acid - 1.5 - 2.5
Talc - Rest

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