RU2145497C1 - Agent for treatment of suppurative-necrotic processes - Google Patents

Abstract

FIELD: medicine, pharmacy. SUBSTANCE: invention proposes ointment for treatment of suppurative-necrotic processes. Agent has the following components, wt.-%: of loxacin 0.05-0.50; trimecain or lidocaine 1.00-6.00; protease C 0.50-3.00; proxanol-268 15-25; propylene glycol 25.0-78.4; polyethylene oxide-400 5-20 and purified water - the rest up to 100. Agent shows the complex effect on damaged zones and ensures to reach the high level of multidirected specific activity at simultaneous decrease or elimination of negative adverse effects. EFFECT: enhanced effectiveness of agent. 8 tbl, 4 ex

Description

 The invention relates to medicine and the pharmaceutical industry, in particular to the creation and production of agents for the treatment of purulent-necrotic processes.

 Known antimicrobial ointment "Dioxol" containing dioxidine, trimecaine, methyluracil, polyethylene oxide-1500 and polyethylene oxide-400. The drug is used in the treatment of purulent wounds, burns, pleural empyema, thrombophlebitis, endometritis, ulcerative necrotic stomatitis, exudative-inflammatory processes on the skin [1].

 A known ointment "Asperase" containing the proteolytic enzyme asperase, glycerin, citric acid, propylene glycol, sodium disubstituted phosphate, petroleum jelly, emulsifier N 1 and distilled water [2].

 Known drug ointment "Iruksol" containing in its composition in 1 g of 10 mg of chloramphenicol and 0.6 g of clostridiopeptidase A with concomitant enzymes in a lipophilic anhydrous basis. The drug has an antimicrobial effect, helping to cleanse wounds from necrotic tissues, accelerating the healing process of purulent wounds [3].

 Closest to the claimed is the drug "Levosin" - a combined ointment containing levomycetin, sulfadimethoxine, methyluracil, trimecaine, polyethylene oxide-1500 and polyethylene oxide-400. The drug has a pronounced antimicrobial, anti-inflammatory, necrolytic and analgesic effect and is used to treat purulent wounds in the first phase of the inflammatory process [4].

 The disadvantages of the prototype and analogues include the fact that they have less pronounced antimicrobial activity both in strength and in the breadth of the spectrum of action; do not possess directed necrolytic activity, providing total lysis of non-viable tissues, including collagen; do not have a prolonged dehydrating effect in the affected area, while protecting normal healthy tissues from excessive dehydration.

 The basis of the invention is the task of creating a tool for the treatment of purulent-necrotic processes by such selection of components, which as a result of a complex effect on the affected areas would achieve a high level of multidirectional specific activity while reducing or eliminating negative side effects.

The problem is solved in that the agent for the treatment of purulent-necrotic processes, containing antibacterial and local anesthetics, a gelling agent and polyethylene oxide-400, in accordance with the invention contains ofloxacin as an antibacterial agent, trimecain or lidocaine as a local anesthetic, and proxanol as a gelling agent -268, and also additionally contains protease-C, propylene glycol and purified water in the following ratio, wt.%:
Ofloxacin - 0.05 - 0.50
Trimecaine or lidocaine - 1.00 - 6.00
Protease-C - 0.50 - 3.00
Proxanol-268 - 15.00 - 25.00
Propylene glycol - 25.00 - 78.40
Polyethylene oxide-400 - 5.00 - 20.00
Purified Water - Else
The technical result obtained by carrying out the invention is expressed in the manifestation of a high level of multidirectional specific activity with a simultaneous reduction and exclusion of negative side effects.

 The claimed tool is approved for medical use for the following reasons: in surgery for the treatment of infected wounds (the first phase of the wound process) with zones of necrosis of various localization and genesis, including pressure sores, trophic ulcers, diabetic angiopathies, suppurative postoperative wounds, etc. in combustiology for the treatment of infected burns of the II-IV degree in the stage of scab rejection to prepare burn wounds for autodermoplasty; in traumatology for the treatment of purulent-necrotic soft tissue wounds; in radiation medicine for the treatment of radiation ulcers in the erosive-necrotic phase.

We give specific examples of the invention:
Example 1. The inventive tool is obtained by dissolving ofloxacin and trimecaine in water by heating and stirring until the drugs are completely dissolved. An ointment base is then prepared by mixing proxanol-268, propylene glycol and polyethylene oxide-400, after which the resulting mixture is heated with stirring until complete dissolution of proxanol-268. An aqueous solution of ofloxacin and trimecaine is introduced into the molten ointment base, after which the resulting mass is cooled with stirring to 35-40 ^o C. Then, protease-C is introduced into the ointment with stirring until a homogeneous mass is obtained, which is cooled to 25 ^o C and packaged in tubes or glass jars of orange color.

The inventive tool has the following ratio of components, wt.% (The example provides information about the regulatory documentation, in accordance with which the components are produced):
Ofloxacin (VFS 42U-1 / 4-281-96) - 0.10
Trimecaine (FS 42-2390-92) - 3.00
Protease-C (VFS 42-2124-92) - 2.00
Proxanol-268 (TU 6-14-14-164-87) - 19.00
Propylene glycol (VFS 42-1594-86) - 58.30
Polyethylene oxide-400 (FS 42-1242-79) - 14.60
Purified water (FS 42-2619-89) - The rest
Example 2. The inventive tool is obtained by dissolving ofloxacin and lidocaine in purified water by heating and stirring until the drugs are completely dissolved. An ointment base is then prepared by mixing proxanol-268, propylene glycol and polyethylene oxide-400, after which the resulting mixture is heated with stirring until complete dissolution of proxanol-268. An aqueous solution of ofloxacin and lidocaine is introduced into the molten ointment base, after which the resulting mass is cooled with stirring to 35-40 ^o C. Then, protease-C is introduced into the ointment with stirring until a homogeneous mass is obtained, which is cooled to 25 ^o C and packaged in tubes or glass jars of orange color.

The inventive tool has the following ratio of components, wt.%:
Ofloxacin - 0.10
Lidocaine (VFS 42-2080-91) - 3.00
Protease-C - 2.00
Proxanol-268 - 19.00
Propylene glycol - 58.30
Polyethylene Oxide-400 - 14.60
Purified Water - Else
Example 3. The inventive tool is obtained analogously to examples 1 and 2 and has the following ratio of components, wt.%:
Ofloxacin - 0.05
Trimecaine or lidocaine - 1.00
Protease-C - 0.50
Proxanol-268 - 15.00
Propylene glycol - 78.40
Polyethylene Oxide-400 - 5.00
Purified Water - Else
Example 4. The inventive tool is obtained analogously to examples 1 and 2 and has the following ratio of components, wt.%:
Ofloxacin - 0.05
Trimecaine or lidocaine - 6.00
Protease-C - 3.00
Proxanol-268 - 25.00
Propylene glycol - 35.50
Polyethylene oxide-400 - 20.00
Purified Water - Else
The qualitative and quantitative composition of the claimed drug completely solves the task of the invention to create a highly effective drug for the treatment of purulent-inflammatory processes of various etiologies.

The main active substance ofloxacin is selected from a number of antibiotics having a fluoroquinoline structure as one of the most active (including ciprinol and pefloxacin). Gram-negative bacteria exhibit high sensitivity to these fluoroquinolines, gram-positive bacteria are less sensitive, although their MIC of ₉₀ to staphylococcus is 0.5-1 mg / ml, including strains resistant to penicillin, methicillin, gentamicin. This property ofloxacin is especially important in the context of the growing antibiotic resistance of modern wound microflora, which determined a selective decrease in their sensitivity to certain multicomponent ointments. So, Levosin ointment, which contains the antibiotic chloramphenicol, the antibacterial effect of which is supplemented by sulfadimethoxin, relatively weakly inhibits the growth of clinical strains of Escherichia coli and Pseudomonas aeruginosa. Dioxol ointment, which contains dioxidine, is inactive against most gram-positive microorganisms. The quantitative content of ofloxacin in the claimed composition (0.05-0.5%) is necessary and sufficient for the manifestation of its specific activity at a given level.

The proteolytic enzyme protease-C is selected to perform the function of cleansing wounds from necrotic tissues. Of the therapeutic methods, the most promising and biologically acceptable today is the method associated with the local use of proteolytic enzymes, due to the following advantages:
1. Selectivity of action, since enzymes lyse only dead tissue and, unlike surgical or chemical necrectomy, they do not violate healthy areas of the skin, which can be foci of islet granulation and epithelization.

 2. Enzymatic cleaning of wounds is the most physiological method, since in natural conditions, proteolytic enzymes are also released during tissue alteration.

 3. Proteolytic enzymes usually have a fibrinolytic effect, which plays a large role in wound healing, as long-healing wounds of various etiologies are characterized by a low level of fibrinolytic activity.

 4. The use of enzymes in the treatment of purulent wounds reduces the antibiotic resistance of their microflora, reduces its virulence.

 The experimental results are given in table. 1-8.

 The concentration of protease-C in the composition of the claimed funds (0.5-3%) was determined experimentally in comparison with analogues containing enzymes; ointment "Iruksol", ointment with the enzyme "Asperase", aqueous solutions of trypsin of various concentrations. In the table. 4-5 are the results of studies confirming the benefits of Oflotrimol-P ointment containing proteolytic protease-C enzyme in the declared quantitative values.

 Introduction to the composition of the claimed funds of local anesthetics - trimecaine or lidocaine, is reasonable. The need for local anesthesia in the 1st phase of the wound process is due to the fact that many purulent-necrotic processes are accompanied by severe pain. Ointment bases with pronounced dehydrating activity, with these pathologies also cause pain. When applying proteolytic enzymes to the wounds, a burning sensation may appear. The choice of trimecain and lidocaine from a number of other anesthetics is also justified: trimecaine is 3 times stronger than the strength and duration of the local anesthetic effect. Trimecaine, like lidocaine, has antiarrhythmic properties and retains its activity (unlike novocaine) in an acidic environment, which is characterized by purulent wounds.

 The concentration of trimecaine and lidocaine in the inventive composition was determined experimentally in comparison with 2% aqueous solutions of these substances. As follows from the results obtained, the effect of trimecaine and lidocaine in the composition of ointments is dose-dependent: the greatest increase in the anesthetic effect is observed with an increase in the concentration of anesthetics from 1 to 3%. A further increase in their concentration (up to 6%) does not lead to a significant increase in the local anesthetic effect, therefore, an increase in concentration above 3% is irrational.

 During the experiments, it was found that ointments with studied concentrations of anesthetics quickly reduce the pain sensitivity of animals (e.g. rats). So, already at the 10th minute after applying the ointments, there is a significant difference in their action compared to the ointment base. The most intense effect of ointments with various concentrations of anesthetics is manifested in the period from 30 to 90 minutes after their application. However, by 120 min, the pain sensitivity of rats does not return to the initial one. Such a duration of the local anesthetic effect of ointments distinguishes them from the action of anesthetic solutions, the maximum effect time of which is 10 minutes, and by the 60th minute the pain sensitivity of the rats returns to the initial level.

 The inventive tool is created on a hydrophilic basis, the composition of which largely determines the level of fulfillment of the main purpose of the drug - the complete recovery of the patient. So, the dehydrating effect of the basis of the claimed drug is manifested both in relation to inflammatory tissue changes, and on the pathogenic microflora contained in them. Dehydration of microbial cells is accompanied by an increase in their sensitivity to antimicrobials, and the elimination of tissue hyperhydration leads to the restoration of microcirculation and normalization of metabolic processes. At the same time, the polymer base of the ointment binds wound toxins of microbial and tissue genesis, thereby creating favorable conditions for the manifestation of local cellular immunity. As a result of this, the periods of relief of the perifocal reaction and purification of wounds from purulent-necrotic sequestration are significantly reduced (1.5-2 times).

 Failure to comply with the claimed qualitative and quantitative values of the basis of the ointment leads to a violation of the physico-chemical and technological characteristics of the drug, and therefore, to a decrease in the level of its specific activity.

 The following are the results of clinical trials of the claimed drug in comparison with the prototype tool.

 All patients with acute purulent processes of soft tissues and suppuration of postoperative wounds under general anesthesia were treated with purulent foci with the removal of non-viable tissues. Then the surface was treated with a solution of hydrogen peroxide, hemostasis was performed and ointment was applied. In the internal cavity (abscesses), the ointment was injected with a syringe after it was melted in a thermostat. In the group of burn patients, a toilet for burn wounds was performed, bubbles were opened, exfoliated necrotic epidermis was removed, then ointment was applied. Subsequent dressings were performed once a day until the wounds were completely cleansed and granulations appeared.

 In the control group, treatment was carried out with Levosin ointment (Table 6).

 Thus, the claimed drug, having a multidirectional effect in the absence of undesirable side effects, is effective in the treatment of purulent-inflammatory processes of various etiologies.

Sources of information
1. Pertsev I.M., Datsenko V.M., Gunko V.G. Development of multidirectional drugs on the purulent-inflammatory process: substantiation of the composition, production, clinical experience. Pharmac. journal - 1991, N 3, p. 56-61.

 2. RF patent N 1729513, A 61 K 37/48, 1992.

 3. Metyashin I.I. et al. Experience in the treatment of purulent wounds with Iruxol. Owls honey. - 1991, N 3, p. 65-68.

 4. Pertsev I. M., Datsenko B. M., Gunko V. G. Development of multidirectional drugs for the purulent-inflammatory process: substantiation of the composition, production, clinical experience and application. Pharmac. journal - 1991, N 3, p. 56-61.

Claims (1)

An agent for the treatment of purulent-necrotic processes, containing antibacterial and local anesthetics, a gelling agent and polyethylene oxide-400, characterized in that it contains oflocoacin as an antibacterial agent, trimecain or lidocaine as a local anesthetic, and proxanol-268 as a gelling agent, and also contains protease-C, propylene glycol and purified water in the following ratio of components, wt.%:
Ofloxacin - 0.05 - 0.50
Trimecaine or lidocaine - 1.00 - 6.00
Protease-C - 0.50 - 3.00
Proxanol-268 - 15.00 - 25.00
Propylene glycol - 25.00 - 78.40
Polyethylene oxide-400 - 5.00 - 20.00
Purified Water - Else

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