Vitamin e and its esters for the local treatment of diseases of the mucous membrane


(57) Abstract:

The proposed use of vitamin E or its esters as the sole active ingredient of the medicinal product for the treatment of genital herpes, epitaxis, pathology of the oral mucosa and the mucosa of the vagina. The invention expands the Arsenal of tools specified destination. 6 C.p. f-crystals.

The scope of the invention

The present invention relates to the use of a-tocopherol (in racemic form (d, 1, or as a pure enantiomer d, 1), also known as vitamin E and its esters with carboxylic acids and, in particular, vitamin E acetate for therapeutic treatment of diseases of the mucosa.

Known level

As was shown by the same applicant in the previous patent application WO-A-97/45098, vitamin E and its derivatives are substances that effect attributed to them antioxidant properties and ability to make free radicals are widely used in the cosmetic industry when creating compositions for treating or preventing skin diseases. On these grounds vitamin E and its derivatives are very often incorporated in concentrations of from 0.5 to 10% in kometiani of the aging process. Actually, the clinical significance of action of vitamin E and called the effect of slowing the aging process on skin level has never been observed in controlled in vivo studies.

In the application EP-A-0158090 described compositions for topical application, containing vitamin E to 20% (preferably up to 10%) by weight in conjunction with other active ingredients, emulsifiers and fillers. In this application claims apply to the use of such compositions for the treatment of eczema, skin inflammation and irritation, skin allergies, excessive skin pigmentation, etc., although experimental confirmation is given only for cases applying lipstick containing 8% deesterification vitamin E to prevent sun or radiation erythema.

In the above-mentioned application WO 97/45098 describes the use of esters of vitamin E and, in particular, vitamin E acetate as cosmetic products for local use and as a special component used in the production of drugs for the local treatment of pathological conditions of the skin.

Study was made possible therapeutic effect of esters of tocopherol in the local application in closely the General description applies tocopherol acetate as the preferred example of the compounds according to the present invention.

Disclosure of the invention

In accordance with the present invention tocopherol acetate can be used "as is" as a drug for topical use on mucous membranes with different types of epithelium of the mucous membrane due to its hydrophobic qualities ointment with protective properties that help to reepithelization, or normalization epithelium damaged due to various pathological conditions.

Oiliness and physiological affinity with biological membranes give a theoretical basis to consider tocopherol as the equivalent of a phospholipid. Its molecular structure with one non-polar and one polar component is actually similar to the molecular structure of the phospholipid. Therefore, we can assume about the possibility of its new use as a medicinal product on the level of the mucous membrane to restore and reintegrative lipid/phospholipid component of the secretion of mucous in the cases when due to various pathologies in different mucous membranes (e.g. mouth, nose, eye, vaginal, rectal) occurs qualitative and quantitative deficiency of secret with strong Nenets, which prevents the evaporation of the water component or replaces water component when it is also in short supply.

The main advantages of the new use of tocopherol as polypide" at the level of the mucosa are his absolute affinity with other biological membranes, as it is a physiological molecule, usually present in biological and cellular membranes man, not an alien molecule, like the others, still used substances (e.g. mineral oils, glycols, polyalcohol), and its molecular is very similar to the phospholipid structure of the polar oil, and so it can be combined with the aqueous phase secretion of mucous, to replace the lipid component of the phase, when it lacks one of the many reasons.

Application of tocopherol on mucous membranes as a substitute for lipid component as at the cellular level and at the level of secret, is therefore innovation.

Another significant advantage is that this "membrane molecule", and it shows two important factors biological effects on biological membranes - "stabilizing effect" and "member chornomu the affinity, thereby increasing the resistance of the latter to the influence of various (angiogenic, inflammatory, chemical and physical) stimuli. This integration due to the affinity has a place for the cell membranes of various cell types at the level of the mucosa and submucosa (for example, epithelial cells, mucous membranes of the fat cells, cells of Langerhans, fibroblasts, endothelial cells of blood vessels), and the membranes of intracellular organelles (e.g. mitochondria, agranular and granular endoplasmic reticulum, nucleosomes). As a result of this integration vitamin E modulates as the "first messenger" several membrane signals, activating, inactivating, or otherwise affecting intracellular metabolic pathways (second messengers) various biochemical methods for different types of cells involved in the process (for example, activation of protein kinases, or cyclic phosphodiesterase AMR; regulation of access ionizirovannoi of calcium into the cells; degranulation of mast cells; regulation of signal cell proliferation). This, in part, may explain the unexpected effects that have been observed when using vitamin E on the level of the mucosa.

To disease, when L", include dryness and itching of the mucous membranes of the oral cavity, vaginal, rectal, nasal and eye, aphthous ulcers, stomatitis, keratoconjunctivitis, keratitis, caratage, ulcer of cornea, deepithelization cornea, membranous rhinitis, nasal vestibulitis, atrophic vaginitis, cervical ectropion, follicular vulva, erythematous vulva, radiation vulva, genital herpes, anal itching, encopresis have, prolapse of the rectum.

Tocopherol and its derivatives, in particular tocopherol acetate, the local application does not cause microbial infection and complications of conservative treatment, since microorganisms may not be distributed in pure tocopherol or tocopherol derivatives, In cases where, however, the health authorities of any country requires the introduction of additional antimicrobial agents or preservatives, it is, of course, can be implemented using conventional techniques of pharmaceutical technology.

Tocopherol acetate can also be used in combination with antibiotics or antifungal means, when there is contamination by microorganisms, or with other active principles, such as steroidal and non-steroidal protivovospalitel by application of tocopherol acetate, if possible, pre-cooled in the refrigerator, directly on the mucous membrane or the use of vaginal or rectal suppositories, or use it in combination with the above-mentioned current basis.

Suppositories can be prepared using, for example, gelatin or glycerin filler, as described in F. U. (Italian Pharmacopoeia) VIII (water, glycerin, gelatin, 25, 65, and 10%, respectively).

Ways of carrying out the invention

Below are some examples of topical application of tocopherol acetate "as is" on various mucous membranes.

The mucous membrane of the mouth

In the mouth and on the lips of tocopherol acetate was used "as is", i.e., undiluted by any other substances, in various pathological situations, including dryness of the mucous membranes of the oral cavity. Examples of such pathological conditions are recurrent aphthous ulcers, stomatitis, and glossitis.

Recurrent aphthous ulcers

Recurrent aphthous ulcers are the most common lesions of the mucous membranes of the oral cavity and are found in 10-30% of the population. The exact cause is unknown, although considered the e and bacterial infections (particularly Streptococcus sanguis and Streptococcus mitis).

There are, however, important predisposing factors such as trauma, endocrine disorders, emotional stress, allergies. Women aphthous ulcers may occur in cycles, a few days before the onset of menstruation. Advanced theoretical assumption that humoral and cellular immunity to antigens mucosa plays an important role in the determinism of the lesions.

Aphthous ulcers on the degree of clinical manifestations can be divided into three types - small, large and herpetiformis.

The differential diagnosis should be kept in mind ulcer syndrome Bachata, because they very often appear earlier than any other characteristic clinical manifestations of the syndrome.

Minor aphthous ulcers

Minor aphthous ulcers are the most frequent clinical form. They are small (2-6 mm in diameter), oval shaped, very painful, covered with yellowish-white crust (necrotic tissue), clearly delimited and surrounded by erythematous ring. They can be single or multiple (2 to 6), usually keep 5-8 days, and then gradually descend, leaving no traces.

They often recur after 1-5 months and almost always hit the "moving" mucous abolita palate and gums.

Vitamin E acetate was administered in 50 cases, patients from 8 to 40 years. It was applied topically on the damaged mucous membrane 3-4 times a day (0.2-0.3 ml per application) for a few days. The most important therapeutic purposes were applications directly before a night's sleep (and afternoon NAPs, if possible), because in these cases the drug spent a long time in contact with aftoi. All patients were encouraged to apply tocopherol acetate at a temperature of about 4o(Chilled), because at this temperature, it was thicker and easier deposited.

In all cases, there were subjective (reduction burning and pain) and objective improvement, and the treatment period was reduced to 3-6 days (instead of 8-10 days).


Stomatitis is an inflammation of the mucous membranes of the oral cavity, causes various

Drug-induced stomatitis is caused by hypersensitivity to an ever used drugs (e.g., antipyretic, sulfonamides, antibiotics, barbiturates).

Burn stomatitis associated with thermal effects (food, dining items, boiling liquids) or called alkalis (used, for example, in the treatment of teeth).

is whanau, used in the treatment of teeth).

Stomatitis when wearing dentures associated with injuries, recurring in the same place.

Chemical stomatitis is caused by contact with irritants (high-alcohol, alcohol, or acetylsalicylic acid for toothache; eugenol or acrylic resins in dentistry).

Radiation stomatitis is a result of radiation treatment of malignant tumors of the oral cavity, head and neck.

Stomatitis in chemotherapy is a significant complication during treatment of cancer patients by the methods of chemotherapy.

Tocopherol acetate was used in 50 cases of disease of different origin. For several days were carried out daily 2-3 application of tocopherol acetate, cooled in the refrigerator up to 4oWith, because it becomes thicker and easier to apply at this temperature. Applique was applied directly to affected areas in the anterior oral cavity (0.2-0.3 ml per application) or tsp (2 drops per reception) in cases of lesions in the posterior part of the mouth, usually at night or afternoon before going to sleep, when it was possible.

As a result of treatment achieved as subje is called viruses; here are the most important and relevant from a clinical and epidemiological point of view are cases caused by herpesviruses.

You can select primary herpetic gingivostomatitis, secondary herpetic stomatitis, herpes lips, herpes zoster and chickenpox. Other viruses can cause disease, these include viruses Coxsackie and echo viruses that can cause herpangina or defeat the anterior of the mouth.

Tocopherol acetate was used in 50 cases of viral stomatitis in children aged 1 to 10 years. It was applied (chilled in the refrigerator to a temperature of about 4oC) directly on the affected areas of the inner part of the mouth (twice a day, preferably before a night's sleep, and before afternoon in young children, 0.2-0.3 ml per application) and was given with a teaspoon (2 drops twice a day) in the cases when the affected area was in the back part of the mouth.

These applications gave both subjective and objective positive results, decreased the number of attacks of crying, increased food intake, decreased the number of cases, when the children woke up at night, accelerated salaciously pathological situations, characterized by deficits or changes in the tear film (delacreme) or deepithelization conjunctiva or cornea, on the assumption that the tocopherol can prevent the evaporation of the tear film and to promote reepithelization conjunctiva and cornea. Although the tear film and is not part of the structure of the cornea, but is closely linked and contributed its share in the preservation of anatomic and functional unity of the epithelium.

It forms a smooth optical surface of the cornea and thus prevents possible modification of the image; while in contact with the atmosphere, it is the primary source of oxygen to the cornea, which is devoid of blood vessels. In addition, it contains numerous substances with antibacterial properties and growth factors that are produced by the lacrimal glands and involved in the physiological processes of restoration of the cornea. Finally, she washes the eye surface, carrying away the exfoliated cells and foreign particles.

In the tear film, whose thickness is about 7 PM, it is possible to distinguish three layers. The innermost, which are in direct contact with the surface of the cornea consists of the Lenka carries two main functions - slow evaporation of the underlying aqueous component and to lubricate the eyelids during their movement on the eyeball.

The corneal epithelium is a complex nitratenitrogen squamous epithelium, consisting of a surface layer of squamous cells, an intermediate layer of the pterygoid (so named because of their krylovnot, i.e. chrysopogon aperture) cells and a single layer of basal cylindrical cells.

The epithelium of the cornea, being in direct contact with the external environment, not only serves as a barrier for pathological particles contained in the environment, but also must have the ability to quickly recover, as can be easily injured. For injuries of any nature that is causing the continuous dilution of the corneal epithelium, but not affecting membrane of Bowman, should the process of reepithelization, through which healing occurs for 4-7 days.

If the damage affects the entire surface of the cornea and beyond the limb, they reveal different mechanisms of recovery - damage to stem cells in the basal epithelium of the limb causes growth of conjunctival epithelium on the cornea followed by neovascularization of the cornea.

In General, the deepithelization outer cornea treated with medicated eye drops or ointments that help reepithelization and relieve pain. The most widely used drugs such as xanthopterin, retinol, carboxymethylcellulose, hyaluronic acid, N-acetylcysteine.

However, none of them showed a specific effect of reepithelization.

In this regard, the search for new therapeutic options is an urgent need of ophthalmology.

The use of tocopherol acetate was regarded as effective on the assumption that its use can prevent the evaporation of the tear film, to restore its lipid component (replacement of or in combination with external lipid layer of the film), to lubricate the eyelids during their movement on the eyeball and to contribute to reepithelization cornea.

Finally tocopherol acetate can act as a kind of "artificial tear". It should be noted that all ointments may be slightly disturbed, as they temporarily reduce the current lacrimal fluid, when the eye is opened and taksoobraznye, tocopherol acetate was applied topically for various pathological conditions of the eye and caused a significant subjective improvements in significant mitigation of symptoms and objective improvement of the clinical picture until cure.

Examples of such pathological conditions are delacreme, keratoconjunctivitis sicca, filamentary keratoconjunctivitis, iatrogenic keratoconjunctivitis, neuroparalytic keratitis, seasonal keratoconjunctivitis, recurrent caratage, deepithelization the cornea, caused by foreign bodies, ulcers of the cornea, caused by chemical agents, caratage when photorefractive keratectomy and lamellar keratoplasty.

Keratoconjunctivitis sicca, filamentary keratoconjunctivitis, iatrogenic keratoconjunctivitis

These diseases have a number of clinical signs caused by insufficient or disturbed ketopropane. Since there is a close relationship between the surface of the cornea and the tear film, the cases of damage to the outer cornea from eye dryness can be attributed on account of insufficient education of one of the components of tears, and on account of changes in the morphology of the corneal epithelium that m is elianne damage and ulceration.

Vitamin E acetate topically applied to the eye 3-5 times per day in the amount of 0.2 ml per application in 5 cases, a simple dry keratoconjunctivitis, in 5 cases epitheliopathy caused by the development of scar on the eyelids, in 3 cases epitheliopathy caused by paralysis of the VII cranial nerve, and in 5 cases a night of dry eye (then it was used only at night).

In all these cases, a simple topical application of tocopherol acetate gave a positive result. Within 48 hours disappeared symptoms such as pain, feeling of a foreign body, photophobia and lacrimation, accompanied conjunctival hyperemia and noticeable blepharospasm. Examination using a slit lamp showed the production fluorescein-sensitive areas in the first 24-48 hours. Because it was a chronic pathology, the use lasted from several months to two years. Clinical improvement noted since the beginning of the treatment lasted all this time. None of the patients during treatment showed no Allergy to the tocopherol acetate.

Keratitis caused by physical agents

Causes of keratitis caused by physical agents, can be various factors - tricias, ultraviolet oblucenia when Nesmachniy palpebral fissure, 3-4 times a day (0.2 ml per application) for three days. In all cases, the symptoms disappeared after the first few applications and keratitis was cured for three days.

When tricheuse the treatment lasted year-round, to prevent possible recurrence of the disease.

Neuroparalytic keratitis

In 5 cases of ulcers of the cornea due to paralysis of the V cranial nerve topical application of pure tocopherol acetate in the eye (3-4 times a day, 0.2 ml per application) after 7 days was given a full production ulcers. In these cases, vitamin E acetate was together with antibiotic (ofloxacin) to resorption ulcers; then vitamin E acetate topically long been used 2-3 times a day in order to avoid relapse.

Seasonal keratoconjunctivitis

In 5 cases of seasonal keratoconjunctivitis with corneal ulceration topical application of tocopherol acetate (3-4 times per day, 0.2 ml per application) together with local corticosteroid therapy and aspirin oral gave a positive result, improved the symptoms of ulcerative lesions, blepharospasm and secretion of thick secretion of mucous, achieved faster healing ulcerative lesions, which took only 5 days.

Treatment about September) as follows: tocopherol acetate topically in combination with antihistaminic drug topically three times a day for 7-10 days and twice a day for 20-30 days then antihistaminic agent topically twice a day and tocopherol acetate only once a day, in the evening before bedtime.

In four cases, seasonal keratoconjunctivitis in the absence of ulcerations, but when there is a "mosaic" of papillae, topical application of tocopherol acetate (at a dose of 0.2 ml) in combination with local corticosteroid therapy three times a day for 15 days, and then tocopherol acetate topically in combination with antihistamines tool locally in progressively decreasing the dose, resulted in 6-7 months to a considerable reduction of papillae in three cases and to their extinction in one case.

When treating disappeared sensation of "sand in the eye" and the feeling of eye pain in the morning upon awakening, there was a significant subjective and objective (redness of the conjunctiva, the size of the "mosaic" of papillae) improvements in medical examinations from April to September.

Recurrent caratage

Vitamin E acetate was used in 5 cases of recurrent kertanguy after mechanical decapitalization damaged epithelium. It was used three times per day (0.2 ml per application) for 4 days together with non-steroidal anti-inflammatory Lakers epitelizatia cornea after three days of treatment. Then the treatment continued for additional five days only at night.

Ulceration of the cornea, caused by chemical agents

Topical application of vitamin E acetate in this ocular pathology caused positive results.

It was used (3-4 times per day, 0.2 ml per application for 5-6 days, and then only once a day, in the evening, within 3-4 days after reepithelization) in 5 cases of ulcers of the cornea due to alkaline substances: 1 - contact with ammonia, 2 - sulfuric acid, 2 - with caustic soda.

Immediately after the first application decreased subjective sharp burning sensation and "sand in the eye"; within 48 hours came the extensive production of the affected area in three cases of burns ammonia and sulfuric acid. In one case, burn caustic soda, when was not affected basal membrane production occurred after 4 days, but in the other case, although the symptoms had improved, there was no marked recovery in three days; in this case was carried out surgical treatment.

The deepithelization when photorefractive keratectomy and lamellar keratoplasty

When photorefractive keratectomy epithelium was removed before then another 5 days reducing the number of applications to one evening, continued year-round), was achieved by the production of the cornea for three days in 5 of the cases under consideration. When this ocular pathology was also observed striking alleviation of subjective feelings.

When lamellar keratoplasty epithelium was fully restored, the methodology was adjusted depending on the primary pathology that required intervention. Especially when lamellar keratoplasty because of vascularized lake after chemical burns application of vitamin E acetate (4 times per day, 0.2 ml per application for 4-5 days, then 5 days, reducing the number of applications to one in the evening, continue all the year round) gave positive results immediately in the postoperative period, contributing to the rapid process of reepithelization, and in cases of decapitalization in the late postoperative period due to changes in Lesovedenie due to scarring.

When the above-mentioned pathologies topical application of tocopherol acetate proved to be very helpful and also for various phenomena dryness and itching mucous eyes.

The vaginal mucosa and skin-mucosal edges of Amy vulva in various pathological situations as having a softening, protective and lubricating properties (as an ointment), the ability to heal and normalize disrupted epithelium (as a membrane molecule and antioxidant) and as having the ability to restore the balance of vulvovaginal pH (weak acid).

Examples of these pathologies are described below.

Atrophic vaginitis

Atrophic vulvovaginitis is present exclusively in elderly women whose vagina has signs of physiological degeneration caused by progressive gormonozawisimom. This causes a decrease in the elasticity of the vaginal walls and the extreme fragility of the mucosa, which becomes thinner and bleeds easily at the slightest injury, you receive a point bleeding. Symptoms are burning sensation and dryness of the vagina, comes dyspareunia.

Tocopherol acetate was applied topically due to its possible protective actions, the ability to reduce the trophism of the mucous membrane of the vagina and restore the ideal acidity of the ecosystem of the vagina (acetic acid in the molecule of tocopherol acetate makes this molecule subacid).

12 elderly women suffering from atrophic vaginitis, tocopherol acetate naznacilo showed restoration of trophic vaginal tissue at the end of treatment, accompanied by a color change from pale to pink), increasing the elasticity of the tissue and the disappearance point of bleeding.

In addition, in all cases a marked decrease in dyspareunia (pain with intercourse); however, it was significant, up to complete disappearance of pain with intercourse, only in half of the cases.

Cervical ectropion

The term "ectropion" indicates the presence of endocervical glandular epithelium on the outer cervix. This physiological process is a consequence of the hormonal factors that cause hypertrophy and hyperplasia of the endocervical epithelium.

The glandular epithelium is much less resistant to injury and infection than squamous epithelium that lines the intravaginal part of the cervix and vagina, so this process can cause cervicitis. The ectropion contributes a large number of microbes in the vagina and acidic vaginal pH.

We investigated 5 young women, whose average age was 22 years (18-30 years), and who were afflicted with cervical ectropion. All these women were colpocytological examination, a vaginal sample, colposcopy salsa area of 2.5 cm2on the spongy material (Spongostan), and then was applied to the cervix, three times a week for 15 days in order to evaluate the pharmacological effect on the inflammatory aspects of ectropion.

Colposcopy performed before and after treatment showed a significant decrease in the colonization of the cervical division and growth of ectropion and early primary peripheral flat metaplasia.

Follicular vulva

This disease is a result of the inflammatory process of the hair follicle and follicular tissue. It affects exclusively ovolosenie the surface of the vulva, causing the appearance of small papules, separated by normal skin.

Tocopherol acetate was applied topically (1 ml, 2 times a day) in 5 cases, significant clinical improvement was achieved already after a few applications.

Erythematous vulva

This disease is characterized by severe redness and swelling of the vulva. When this form is easily affected skin around acrophobic folds. Symptoms include severe itching and burning. Basically it is caused by injury (Bicycle, horse riding and so on) or allergies (soap, towel, tights, and so on).

Tocopherol acetate PrimeCare was achieved significant mitigation of symptoms, clinical normalization took place within 48-72 hours.

Radiation vulva

It can occur after direct exposure of the vulva during radiotherapy. Radiation damage ranged from simple erythema to swelling of the third degree with ulceration.

Tocopherol acetate in the local application (1 ml, 2 times daily) may be effective medical care due to its protective barrier and calming effect and its ability to restore the epithelium.

The vulvar vestibulitis

Also referred to as micropapillary vulva. This subclinical papovaviruses infectious disease. Velvety view of the medial surface of the small private parts of the lips caused by hyperplasia and hypertrophy of the mucosa. Immunodeficiency, locally transmitted cell, promotes secondary mycotic infection. Symptoms include itching and vulvodynia.

Almost 90% of those 25 women whose treatment was conducted tocopherol acetate (2 ml, twice a day for two weeks) topically to the mucous membrane of the vestibule of the vulva, achieved complete remission of itching and pain of the vulva, while the remaining 10% was not marked signs of improvement.

Barrier and antioxidant DOI shell predgornogo Department, inhibits the development of mycotic process and, thus, contributes to the disappearance of itching and vulvodynia.

The mucous membrane of the rectum and anal skin and mucous hem

Tocopherol acetate topically applied in various pathological conditions of the mucous membranes in the anal and perianal areas and proctitis.

Anal itching

Treatment of seven patients suffering from anal itching, have to proctologic examination does not show apparent organic cause, was conducted tocopherol acetate (0.2-0.4 ml twice a day) for 30 days.

After treatment, 4 patients achieved complete remission, and the remaining three reported satisfactory improvement.

The encopresis have

There are encopresis have two types - weak (partial or random) and strong. In the latter case, the incontinence even in a normal formed stool.

Treatment of 10 patients suffering from a weak encopresis have, and 5 patients suffering from strong encopresis have, was conducted tocopherol acetate (1-2 ml three times a day for 30 days).

At objective inspection noted a significant decrease in osalennosti undoubtedly associated with protection Kocak patients suffered severe form, noted good results.

Ulcerative proctitis

Ulcerative proctitis is a form of ulcerative colitis solely on the rectum; it can also be caused by sexual activity or defeat of ionizing radiation.

Ulcerative proctitis is characterized by weak pryamokishechnye bleeding bright red blood, the use of hemostatic means, and a strange pain in the left quadrants.

Treatment of five patients suffering from proctitis after radiotherapy was conducted tocopherol acetate; tocoferol acetate was given in the amount of 0.8 ml in microcomposite twice a day for 30 days.

All patients felt better light to good. Endoscopy revealed an improvement of the overall picture, the absence of erosive damage and reduce breakage, although still had hypertrophic state.

Prolapsed rectum

Treatment of five patients suffering from prolapse of the rectum and associated inflammation, erosion and cracks mucosa, were vitamin E acetate (0.6 to 0.8 ml three times per day) for one month.

Excellent subjective results had already poslovanje after 15 days showed a significant decrease in osalennosti, the disappearance of the erosion of the mucosa and cracks.

Treatment, which have all lasted many months (two years), helped to keep the achieved results without recurrence of inflammation or erosion fallen mucosa.

Finally, topical application of tocopherol acetate gave significant relief in several cases of dryness and burning of the mucous membrane of the rectum.

The mucous membrane of the nose and skin-mucous border of the nasal vestibule

At the level of the nasal mucosa has also been shown that topical application of tocopherol acetate may be useful in various pathological situations, some of which are described in the examples.

Membranous rhinitis

When many different nature and kind of inflammation of the nasal cavity in the latter are solid filmy selection or serous blood clots. These diseases include infectious rhinitis, weak recurrent epistaxis (nosebleeds), after adenoidectomy and microtraumas (fingers in the nose, especially it is characteristic for children).

In 50 cases, membranous rhinitis application of tocopherol acetate (0.2 ml, 2-3 times a day) for 2-4 days, had a good wosley vestibulitis nose with cracks on the skin

Eczema anticipation of the nose, often with cracks, which is a consequence of acute and chronic rhinitis, in which the selection irritate the skin lining predgornogo Department.

In 100 cases of eczema predgornogo Department (almost all in the cold) application of vitamin E acetate having a softening, protective and revitalizers action to be brought within 48 hours to the disappearance of cracks and normalization of eczematous skin in 3-6 days.


Epistaxis occurs when the rupture of blood vessels in the mucous membrane of the nose for a variety of reasons.

Whenever possible, treated the cause of epistaxis, for these purposes is well suited to local therapy.

When recurrent light epistaxis topical application of tocopherol acetate is useful as an auxiliary treatment due to softening, protective and atopicheskogo action.

Tocopherol acetate was administered (0.2 ml, 2-3 times a day for 15 days) 20 children, who suffered a slight epistaxis as a result of injuries caused by bad habit of constantly sticking fingers in the nose. In all cases, the attacks epistaxis disappeared.

Varicose blood vessels in the area of Valsalva

VariCam children moxibustion these varicose extensions vessels is not very often because of the risk of iatrogenic perforation of the nasal septum.

Tocopherol acetate was applied topically (0.2 ml, 2-3 times a day) for 3 months on the mucous membrane of the nasal septum in 60 children (from 2 to 6 years) who suffered from varicose blood vessels in the area of Valsalva and recurrent epistaxis. In all cases the resulting decrease in the number of attacks epistaxis up to the disappearance, in the course of treatment and medical control is set to improve the trophic mucous membrane of the nose and the macroscopic aspect of themselves varicose extensions vessels.

Tocopherol acetate in the local application showed atroficheskie and protective effects on the epithelium of the nasal mucosa, which is important for predotvrasenija irritation, which, especially in children, can lead to more scratching and nasal bleeding when local varicose changes. These atroficheskie and protective factors proved its positive effect in all States, characterized by dryness and itching of the nasal mucosa.

Ulceration of the mucous membrane of the nose due to foreign bodies

Children are often put in the nose of various foreign bodies that can cause ulcerative lesions of the mucous membrane of the nose.

Tocopherol acetate (0.2 ml, 2-3 times day the disappearance of ulcerations in the control after 7 days of treatment.

The effect of topical application of tocopherol acetate in cases of genital herpes also deserves attention.

Genital herpes

Vitamin E acetate was used for local applications in 20 patients (10 men and 10 women) suffering from genital herpes (aged 16 to 45 years).

In 17 cases, significant improvements were obtained with the application of vitamin E acetate is at least three times a day, in the amount of 0.2-0.4 ml each time.

When vitamin E acetate was used at the first symptoms (pruritus, paresthesia or pain, primary vesicles), it was observed that vesicles do not appear (if originally absent) or covered with a crust within 1-3 days (if originally present) and was a significant acceleration of recovery.

When vitamin E acetate was used already developed herpes diseases (numerous vesicles occurred 1-2 days), new vesicles did not appear, existing lesion had stopped growing and rapidly moved into the cortical phase (1-2 days).

Moreover, immediately after applying disappeared subjective symptoms of burning and/or itching and herpes symptoms.

Only in one case iiireig with them subjective symptoms.

In 2 cases, the absence of clinical response to the use of vitamin E acetate seemed associated with inadequate frequency of use, since when the number of applications during the day increased, the recovery was accelerated.

1. The use of compounds selected from the group consisting of vitamin E and its esters, as the sole active ingredient of the medicinal product for the local treatment of at least one state selected from a number of genital herpes, epistaxis, diseases of the mucous membranes of the oral cavity and mucous membranes of the vagina.

2. Application under item 1, characterized in that the said compound is an ester of vitamin E with a carboxylic acid of the formula R-COOH, where R is alkyl, alkanniny or alkynylaryl the residue containing from 1 to 19 carbon atoms.

3. Application under item 2, characterized in that said carboxylic acid is selected from the group consisting of acetic acid, n-propionic, succinic, and linoleic.

4. Application under item 3, characterized in that the said connection of vitamin E - acetate.

5. Application under item 4, characterized in that the said connection is the only ingredient KJV is th pathologies include aphthous ulcers, stomatitis, glossitis, dryness and itching of the mucous membranes of the oral cavity.

7. Use one of the PP.1-5, characterized in that the mentioned pathologies include atrophic vaginitis, cervical ectropion, dryness and itching of the vaginal mucosa.


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Antiherpetic agent // 2164138
The invention relates to medicine

The invention relates to medicine, namely to endocrinology and dermatology, and can be used to prevent frequent recurrences of herpes simplex
Cosmetic lip // 2159608
The invention relates to cosmetics and medicine and can be used in the prevention and decorative lip care
The invention relates to medicine, namely to ophthalmology, and can be used for the treatment of herpetic eye infections, in particular herpes keratitis

The invention relates to medicine, gynecology, and can be used to treat diseases of the urinary tract

The invention relates to medicine
The invention relates to medicine, in particular to the gynecologist, and can be used for the treatment of obesity
The invention relates to medicine, in particular to obstetrics and gynecology, and can be used for treatment of bacterial vaginosis

The invention relates to medicine and can be used in preventive pharmacology for the preparation of drugs from the blood of the deer

The invention relates to medicine, namely to gynecology, and can be used for the treatment of vaginal candidiasis
The invention relates to medicine, namely to gynecology, and can be used for treatment of bacterial vaginosis

The invention relates to medicine and relates to a medicinal product for the prevention and treatment of urogenital infections for local use

The invention relates to pharmacology and about creating convenient for intravaginal application form new, not previously used in gynecological practice antiseptic plant have antibacterial, antifungal, antiviral activity and activates the reparation of damaged mucosa

The invention relates to veterinary