Dolobene

General characteristics. Structure:

100 g of gel contain:
Active agents:
Heparin sodium 50000 ME
Dekspantenol of 2,500 g
Dimethyl sulfoxide of 90% 16,660 g
(in terms of dry matter) (15,000 g)
Excipients:
The polyacrylic acid of 1,000 - 1,400 g, трометамол 0,200 - 0,300 g, a macrogoal глицерилгидроксистеарат (CO 455 cremophore) of 1,000 g, isopropanol of 35,000 g, rosemary oil of 0,200 g, pines mountain oil of 0,250 g, a citronella grass oil of 0,050 g, the water purified 42,023 - 42,913 g.

Description:
From transparent to slightly muddy and from colourless till slightly yellowish color gel.

Pharmacological properties:

Pharmacodynamics. Dimethyl sulfoxide (DMSO).
DMSO possesses the antiinflammatory, antiedematous and local anesthetizing action.

Antiinflammatory activity is connected with some pharmacological effects, the most significant of which is the inactivation of the hydroxylic radicals which are developed in large numbers during process of an inflammation and having destructive effect on fabrics.

DMSO renders local analgetic effect due to reduction in the rate of carrying out nociceptive (painful) impulses in peripheral neurons. Antiedematous action is provided with an inactivation of hydroxylic radicals and improvement of hypodermic metabolic reaction in the place of use of drug. To a certain extent, the DMSO hygroscopic properties are also responsible for its antiedematous action. DMSO (from 50% and more) gets through biological membranes, including through skin, promoting the best and deeper penetration into fabrics of other medicines applied along with it.

Heparin.
Heparin has antiinflammatory effect, promotes regeneration of connecting fabric due to oppression of activity of hyaluronidase. Heparin shows dozozavisimy antitrombotichesky effect, increasing the inhibiting activity of antithrombin III on activation of a prothrombin and thrombin. Penetration of heparin through healthy skin is dozozavisimy and is confirmed for a dosage, since 300 ME/g.

Dekspantenol.
At topical administration декспантенол it is transformed in skin to pantothenic acid (group B vitamin). Efficiency of a dekspantenol is comparable to efficiency of pantothenic acid. Pantothenic acid as a component of coenzyme A participates in various catabolic and anabolic processes in fabrics, due to improvement of processes of granulation and epithelization promotes regeneration of the damaged sites of skin.

Pharmacokinetics. Dimethyl sulfoxide (DMSO).
Physiological concentration of DMSO normal in a blood plasma makes 40 ng/ml. 6 hours later after putting drug the maximum concentration in a blood plasma reaches 120 ng/ml and remains till 12 o'clock after use. 60 hours later after use concentration of DMSO in a blood plasma reaches the physiological level of 40 ng/ml. 12-25% of the absorbed DMSO are removed within the first 24 hours and 37-48% are removed within 7 days in not changed look through kidneys or in the form of a metabolite (methyl sulphone). 3,5-6% of all DMSO are removed through lungs in the form of methyl thiomethane 6-12 hours later after drug use.

At use on 1 g of a dimethyl sulfoxide 3 times a day within 5 days average content it in a site of application on skin makes 3 mg/g, average content in the subject muscular tissue and a synovial membrane in the place of synovial connection of 7-10 mkg/ml, in synovial fluid - 0,8 mkg/g. Concentration of a dimethyl sulfoxide in a blood plasma makes 0,5 mkg/g. The elimination half-life of DMSO makes 11-14 hours.

Heparin.
At external use heparin is soaked up slightly.

Dekspantenol.
At external use декспантенол it is transformed in skin to pantothenic acid. Good absorption of a dekspantenol is confirmed experimentally.

Indications to use:

• hypostases, hematomas and inflammations of soft tissues, muscles, sinews, tendinous vaginas,
• the closed injuries, bruises,
• injuries of joints with sprain and sinews,
• shoulder epicondylitis ("tennis player's elbow"), tendinites (inflammation of sinews), tendovaginitis (inflammation of tendinous vaginas), bursitis (inflammation of a mucous bag of a joint),
• periarthritis of a shoulder joint,
• acute neuralgia.

Route of administration and doses:

Dolobena should apply with a blanket on skin over an affected area of skin 2-4 times a day.

When using gel under a bandage it is necessary to apply gel and to wait several minutes that it was absorbed by skin and isopropanol evaporated. Then it is possible to apply a hermetic bandage.

Dolobene can be applied at an ionophoresis. Drug is applied under the cathode. Dolobene as contact gel can be applied in ultrasonic therapy (fonoforeza). Active agents of gel supplement therapeutic action of ultrasonic waves. Duration of treatment depends on expressiveness of symptoms and disease severity.

Features of use:

The site of application of gel has to be free from other medicines, cosmetics or any chemical means. Dolobena cannot apply on mucous membranes of eyes, a nose, a mouth, open wounds or on the damaged sites of skin (owing to radiation, a strong sunblister, postoperative hems).

During treatment by drug the skin photosensitivity therefore during its use it is necessary to limit intensive solar bathtubs and visit of a sunbed can amplify. In case of skin reactions treatment has to be stopped. Because of high absorption of a dimethyl sulfoxide it is not necessary to use Dolobene in a combination with other ointments and gels.

Side effects:

Local skin reactions (reddening, an itch, burning sensation in a gel site of application) which usually disappear during further treatment are possible. Because of the maintenance of DMSO or other components of drug emergence of skin allergic reaction is sometimes possible.

In rare instances during use of drug for some patients the garlic smell from a mouth can appear. The smell is caused by the methyl thiomethane which is a product of metabolism of a dimethyl sulfoxide. Change of the flavoring feelings disappearing in a few minutes after putting gel is possible.

In isolated cases emergence of allergic reactions of immediate type (a small tortoiseshell, a Quincke's edema) is possible. Extremely seldom when putting drug on extensive body parts developing of nausea, diarrhea, difficulty of breath, a headache, a fever is possible.

Interaction with other medicines:

Along with Dolobene's drug their permeability through skin can strengthen putting other medicine. At simultaneous use of drug of Dolobene and non-steroidal anti-inflammatory drug сулиндак development of peripheral neuropathy is possible.

Contraindications:

• hypersensitivity to one of gel components (active / to excipients),
• bronchial asthma,
• heavy abnormal liver functions, kidneys,
• the expressed disturbances of cardiovascular system,
• pregnancy and period of a lactation,
• age up to 5 years,
• open wounds in a site of application.

Use during pregnancy and during feeding by a breast:

Use during pregnancy.
As data of researches on use of drug for pregnant women are absent, its use during pregnancy is contraindicated.

Use during a lactation.
The dimethyl sulfoxide gets into breast milk therefore in usage time of drug it is necessary to stop feeding of the child a breast.

Overdose:

Data on overdose of drug are absent.

Storage conditions:

To store at a temperature not above 25 °C to Store in the place, unavailable to children! Period of validity: 3 years. Not to apply after expiry date!

Issue conditions:

Without recipe

Packaging:

Gel for external use.
On 50 g or 100 g of drug in the aluminum tubas tightened aluminum foil for control of the first opening with the screwed polymeric cover.
1 tuba together with the application instruction is placed in a cardboard pack.