lyophilizate for solution for injection 3000 IE 5 ampules in box
International non-proprietary name: bovhyarulonidase azoximer
An advanced sustained release enzyme for combined therapy of connective tissue hyperplasia diseases (adhesion, scarring, or fibrous processes).
Used in gynecology, urology, dermatovenerology, pulmonology, orthopedics, surgery, esthetic medicine, and otolaryngology.
Dosage forms: suppositories, and lyophilizate for solution for infusion.
PHARMACHOLOGIC EFFECT
Bovagaluronidase azoxime is a conjugate of the proteolytic enzyme hyaluronidase with a high molecular weight carrier from the group of derivatives of the N-oxide of poly-1,4-ethylene-piperazine. Bovagaluronidase azoxime has the entire spectrum of pharmacological properties inherent in drugs with hyaluronidase activity. The specific substrate of hyaluronidase is glycosaminoglycans (hyaluronic acid, chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate), a "cementing" substance of connective tissue. As a result of hydrolysis (depolymerization), the viscosity of glycosaminoglycans decreases, the ability to bind water and metal ions. As a result, the permeability of tissues increases, their trophic tissues improve, edemas decrease, hematomas dissolve, the elasticity of the scar-altered areas increases, contractures and adhesions are eliminated, joint mobility increases. The effect is most pronounced in the initial stages of the pathological process.
The clinical effect of boviazaluronidase azoxime is significantly higher than the effect of native hyaluronidase. Conjugation increases the stability of the enzyme to the action of temperature and inhibitors, increases its activity and leads to prolongation of the action. The enzymatic activity of boviazaluronidase azoxime is maintained when heated to 37 ° C for 20 days, while native hyaluronidase under the same conditions loses its activity during the day. Bovigialuronidase azoxime preserves the pharmacological properties of the carrier, which possesses chelating, antioxidant, anti-inflammatory and immunomodulating activity.
Bovagaluronidase azoxime is able to bind the iron ions liberated during the hydrolysis of glycosaminoglycans - activators of free radical reactions, hyaluronidase inhibitors and stimulators of collagen synthesis, and thereby suppress the reverse reaction directed to the synthesis of connective tissue components. The polytropic properties of boviazaluronidase azoxime are realized in the expressed antifibrotic action, experimentally proved by biochemical, histological and electron microscopic studies on the model of pneumofibrosis.
Bovagaluronidase azoxime regulates the synthesis of mediators of inflammation (interleukin-1 and TNF?), It can weaken the course of the acute phase of inflammation, increase the humoral immune response and the resistance of the organism to infection. These properties allow the use of boviazaluronidase azoxime during or after surgical treatment to prevent coarse scarring and adhesions. The use of boviazaluronidase azoxime in therapeutic doses during or after surgery does not cause a worsening of postoperative course or progression of the infectious process; does not slow the recovery of bone tissue.
Bovagaluronidase azoxime with co-administration of s / c or in / m introduction increases the absorption of drugs, accelerates anesthesia with the administration of local anesthetics.
Boviataluronidase azoxime refers to practically non-toxic compounds, does not interfere with the normal functioning of the immune system, does not affect the reproductive function of male and female rats, pre- and postnatal development of offspring, does not have a mutagenic and carcinogenic effect. It has been experimentally proved that the irritating and allergic properties of the hyaluronidase enzyme are reduced in bovigialuronidase azoxime. In the therapeutic doses of boviazaluronidase, azoxime is well tolerated by patients.
PHARMACOKINETICS
Suction and distribution
When parenteral administration of boviazaluronidase, azoxime is rapidly absorbed into the systemic circulation and reaches C max in the blood after 20-25 minutes. It is characterized by a high rate of distribution, the half-distribution period is about 0.5 hours. It penetrates into all organs and tissues (including through the BBB and hemato-ophthalmic barrier).
Apparent V d is 0.43 l / kg. Conjugation does not reduce the high bioavailability of the enzyme - bioavailability of at least 90%.
Metabolism and excretion
In the body, hyaluronidase undergoes hydrolysis, and the carrier is metabolized to low-molecular compounds (oligomers), which are excreted mainly through the kidneys in two phases. During the first day through the kidneys, 45-50% are excreted, through the intestine - no more than 3%. Further, the elimination rate slows down, and by 4-5 days the drug is completely eliminated. T 1/2 with an IM injection - 36 hours, with a / c introduction - about 45 hours.
INDICATIONS
The drug is prescribed to adults as part of complex therapy for the treatment and prevention of diseases accompanied by hyperplasia of connective tissue.
In gynecology:
- treatment and prevention of adhesions in the small pelvis with inflammatory diseases of the internal genital organs, incl. tubal peritoneal infertility, intrauterine synechia, chronic endometrium.
In urology:
- treatment of chronic prostatitis;
- Treatment of interstitial cystitis.
In surgery:
- Treatment and prevention of adhesions after surgical interventions on the abdominal organs;
- Hypertrophic scars after injuries, burns, surgeries, pyoderma;
- long-term non-healing wounds.
In dermatovenerology and cosmetology:
- treatment of limited scleroderma;
- treatment of keloid, hypertrophic, emerging scars after pyoderma, trauma, burns, surgeries.
In pulmonology and phthisiology:
- treatment of pneumosclerosis, fibrosing alveolitis;
- Treatment of tuberculosis (cavernous-fibrous, infiltrative, tuberculoma).
In orthopedics:
- Treatment of joint contractures, arthrosis, ankylosing spondylitis, hematoma.
To increase bioavailability:
- with the joint introduction of antibacterial drugs in urology, gynecology, surgery, dermatovenereology, pulmonology, to strengthen the action of local anesthetics.