Pharmaceutical composition for topical treatment of inflammation and method for its preparing

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition and a method for it preparing. The composition comprising effective doses of hyaluronic acid, glycyrrhetinic acid as active components and polyvinylpyrrolidone is used in treatment of morbid inflammatory and ulcerous states of moisture epithelial surfaces, such as mucosa inflammation and Behchet's syndrome. The composition shows favorable effect due to its moistening action.

EFFECT: valuable medicinal and pharmaceutical properties of composition.

6 cl, 3 ex

 

The present invention relates to pharmaceutical compositions containing hyaluronic acid, glycyrrhetic acid and polyvinylpyrrolidone to eliminate painful ulcerative and inflammatory conditions wet surfaces, including the oral cavity, oropharynx, esophagus, vagina, and rectum (including inflammation of mucous membranes, stomatitis, and syndrome behceta, but not limited to.

PRIOR art

The terms "inflammation of the mucous membranes" and "disease" are often used interchangeably, but may include some General differences. "Inflammation of the mucous membrane" describes the toxic inflammatory reaction, followed by the gastrointestinal tract, which can result from exposure to chemotherapeutic agents or ionizing radiation. Inflammation of the mucous membrane typically manifests as erythematous, similar to a burn lesion or in the form of an arbitrary locally diffuse ulcerative lesions.

Stomatitis is an inflammatory reaction affecting the mucous membrane of the mouth, with or without ulceration, which may be caused or exacerbated by drugs, particularly chemotherapeutic treatment, or radiotherapy. The disease can vary from mild to severe; the patient with severe is the disease are not able to take anything by mouth.

Many women aphthous ulceration of the mouth occurs on certain days of the menstrual cycle, and at the same time they have ulcers of the same type in the genital tract, in particular on the vulva and in the vagina. Sometimes it is very heavy and can cause urinary retention, and also requires strong painkillers and sedatives. The most severe form is called the syndrome behceta.

In the following description, the more General term "inflammation of the mucous membrane will also be used to refer to the actual disease. The study of mucosal inflammation illustrates this work confirms the claims.

Erythematous inflammation of mucous membranes may appear three days after exposure to chemotherapy or radiotherapy, but more normal within five to seven days. Progression to ulceration of the mucosal inflammation usually occurs within seven days after the start of chemotherapy and sometimes may reach such a degree of severity that requires cessation of drug treatment. Inflammation of the mucous membrane may cover the oral cavity and the oropharynx and gastrointestinal tract from mouth to anus. In this description the authors of this invention are limited to inflammation of the mucous membrane, poraj the resources readily available area, such as the oral cavity, oropharynx, esophagus and rectum.

Since a high percentage (30-40%) patients receiving chemotherapy develop inflammation of the mucous membrane in varying degrees, there is a critical need for effective appropriate treatment. Today is not actually available no effective methods of treatment, and attempts were made to solve this problem through the use of anaesthetics, antiseptics and measures of oral hygiene, or the temporary relief of symptoms.

In addition, the problem is not limited to patients suffering from cancer, inflammation of the mucosa often occurs in patients with HIV, particularly in Association with Kaposi's sarcoma in patients suffering from non-Hodgkin's lymphoma, in frail elderly patients and patients receiving treatment biological modifiers (BM), such as interleukin-2, tumor necrosis factor (TNF), interferons, lymphocytes activated by lymphokines and the like.

In EP 0444492 disclosed compositions based on high molecular weight hyaluronic acid for the treatment of inflammations in the oral cavity. In GB 2092442 described compositions for the treatment of inflammations in the oral cavity that contains glycyrrhetic acid. The combination of these substances with polyvin what pyrrolidone for the local treatment of inflammation is not described anywhere.

Thus, the present invention is to provide a pharmaceutical composition for the local treatment of inflammation based on the combination of hyaluronic acid, glycyrrhetic acid and polyvinylpyrrolidone, providing effective therapeutic and prophylactic treatment of local inflammation.

Description of the INVENTION

At the moment it has been unexpectedly found that local injection of a pharmaceutical product containing hyaluronic acid, glycyrrhetic acid and polyvinylpyrrolidone, provides an effective therapeutic and prophylactic treatment of mucosal inflammation and disease of different origin and severity, and, more generally, lesions of the oropharynx and esophagus, in particular, lesions caused dental devices, as well as radio - or chemotherapy.

Thus, in the first aspect of the present invention proposed a pharmaceutical composition containing as active ingredient an effective dose of hyaluronic acid, glycyrrhetic acid and polyvinylpyrrolidone in a mixture with excipients and adjuvants, with the formation of viscous and lubricating substances, which remains adhesive to the surface epithelium, suitable for local application on epithelial surfaces, such as Roto the tray and the esophagus, but not limited to.

Another aspect of the present invention relates to the use of hyaluronic acid, glycyrrhetic acid and polyvinylpyrrolidone for the manufacture of drugs for the local treatment of inflammatory conditions of epithelial surfaces, such as mucous membrane of the mouth, but not limited to them, in particular, inflammation of mucous membranes, stomatitis.

DETAILED description of the INVENTION

The compositions of this invention are in the form of a slightly viscous aqueous liquid (gel), which provides film-forming and enveloping effect on epithelial surfaces, such as mucous membranes of the mouth, but not limited to.

Hyaluronic acid is present in a mass percentage concentration in the range from 0.01 to about 5%, preferably about 0.1%. Hyaluronic acid can also be in the form of sodium salt, and preferably biotechnological origin, with a molecular weight in the range from 1.6 to 2.2×106Yes.

Polyvinylpyrrolidone or povidone (PVP), suspendisse and binding agent, widely used in pharmaceutical technology. It is present in the preparations according to this invention in mass percentage concentrations in the range from 1 to 20% by weight, the pre is respectfully from 5 to 10%.

Glycyrrhetic acid may be present in a mass percentage concentration in the range from 0.01 to 3% by mass.

Preferably used povidone high molecular mass, such as povidone from the K-30 to K-120, preferably povidone K-90, having an average molecular weight of about 1000000.

The compositions of this invention may contain suitable excipients for topical administration, such as:

agents that increase viscosity;

- surfactants;

- stabilizing agents, preservatives;

- corrigentov, flavouring agents, sweeteners;

- bioadhesive agents;

- cosolvent.

Examples of these excipients include cellulose derivatives, polymers or copolymers of acrylic or methacrylic acids, ethylene or propylene glycols, polyethoxysiloxane hydrogenated castor oil, ethylenediaminetetraacetic acid (EDTA), sodium benzoate, sodium sorbate or potassium, dextrins, saccharin sodium, aspartame and other excipients commonly used in preparations in the form of solutions for the mouthwash or liquid forms for oral administration.

The compositions of this invention can optionally contain other active ingredients, with additional information, or any other useful activity of the Yu, such as anti-bacterial agents/disinfectants, antifungal agents, analgesics, anti-inflammatory agents, emollients, local anesthetics, and the like. Suitable antimicrobial agents include Quaternary ammonium salts such as benzalkonium chloride.

Finally, the compositions of this invention can be represented by forms with single or multiple doses, for example in the form of sachets, bottles, ampoules, vials and the like.

The dosage will depend on many factors, such as severity, type and duration of the disease, which is treated: in principle, however, the washing or rinsing 10-50 ml, possibly diluted in water, within a time span of approximately two or three minutes three or more times daily, preferably before meals, will be sufficient to provide the optimal therapeutic or preventive effect. Treatment may continue until the attenuation of symptoms, usually within 5-10 days. More prolonged treatment is not contraindicated, given the low toxicity of the components of the preparations according to this invention, if such toxicity at all.

Favorable therapeutic results obtained when CA is on drugs in this invention, are as a result of synergistic interactions between hyaluronic acid, glycyrrhetic acid and polyvinylpyrrolidone, and the ability of this drug to the adhesion to the mucous membrane of the mouth, providing a protective wrapping for vulnerable nerve endings and thereby decrease pain, as well as the activation of scarring and healing damage. In addition, the moisturizing effect of these compositions has a beneficial effect because it protects membranes mucous membranes from additional annoying damage.

The following examples illustrate the invention in more detail.

Example 1

Qualitative and quantitative composition composition

Sodium hyaluronate0,1
Glycyrrhetic acid0,06
PVP9,0
Maltodextrin6,00
Propylene glycol2,94
Potassium sorbate0,3
Sodium benzoate0,3
Hydroxyethylcellulose1,5
Hydrogenated castor oil PEG-400,27
Disodium EDTA0,1
The chloride benzal the deposits 0,5
Odorant (Glycyrrhiza Comp.2717)0,16
Saccharin sodium0,1
Purified waterrest

For preparing the water placed in turbogenerator, then add a mixture of potassium sorbate, sodium benzoate and disodium EDTA, and then hyaluronic acid and maltodextrin. The mixture is stirred after each addition until complete dissolution of the components. Then slowly add PVP with stirring under vacuum (3999 PA (30 mmHg)) to complete solvation. Then add saccharin sodium and hydroxyethyl cellulose, all placed in vacuum and left under stirring until complete solvation. After that add in the following order hydrogenated castor oil 40/OE and the odorant, benzalkonium chloride, and a mixture of propylene glycol and glycyrrhetic acid, stirring after each addition until complete dissolution of the components. After the addition was completed, the mixture is stirred under vacuum for 30 minutes.

For the variant of the present invention, representing a concentrated solution, 10 ml or 15 ml of the composition described above, distributed in sachets or bottles with a single dose, which should be diluted in 30-50 ml of water before use; for option this izaberete the Oia, ready-to-use, composition, described above, is diluted with purified water to a concentration of 50%, and 200 ml or 300 ml distributed in bottles.

Example 2

Clinical trials

Researched thirty patients aged 30 to 60 years, with 10 of them were HIV-infected patients aged 30 to 40 years, receiving treatment against retroviruses. Patients were affected by inflammatory pathologies of the oral cavity of various etiologies:

12 cases of inflammation of the mucous membrane of the oropharynx;

4 cases of aphthous lesions of the oral cavity;

4 cases of post-traumatic lesions;

3 case red flat lichen oral cavity;

3 cases of disease caused by radiotherapy;

3 cases of side effects of surgery of the oral cavity;

1 case of leukoplakia.

Patients were treated with the composition of Example 1 in 15 ml sachet diluted in water at a ratio of 1:4. Slightly viscous solution was kept in the mouth for 2-3 minutes, during which time they were rinsed with bubbles to obtain a homogeneous distribution over the entire surface of the mucous membrane of the oral cavity. The solution is then discarded.

The drug is used three times a day for 60 minutes before a meal for seven days.

By the end of treatment was assessed by the degree of inflammation and damage reduction and disappearance of dysphagia for solid and floor is solid foods and liquids and duration of activity of this product.

After the first application of more than 80% of patients felt within a few hours decrease pain, so had the opportunity to eat. The effect lasted for three or four hours.

The healing of injuries to the mucous membranes of the oral cavity have been observed after 3-4 days of treatment approximately 60% of cases treated. This percentage reached 90% by the end of treatment. In the remaining three cases were preserved pathological condition, but with improved symptoms compared with the beginning of the treatment, providing whatever it was a dramatic improvement in their quality of life and the restoration of normal differentiated diet.

Example 3

Two patients with sore throat (sore throat) were not able to get relief with medication or other agents for local use. Patients were treated with the composition of Example 1 in 15 ml sachet diluted in water at a ratio of 1:4. The solution was kept in the mouth for approximately one minute, during which time they were rinsed to obtain good contact with the tissues of the throat. The solution is then discarded. Within ten minutes, the patient felt a sudden relief of symptoms of angina, which persisted for several hours.

1. Pharmaceutical composition for the local treatment of inflammation, comprising as active ingredient is s effective dose of hyaluronic acid, glycyrrhetic acid and polyvinylpyrrolidone in a mixture with excipients and adjuvants suitable for local administration.

2. The composition according to claim 1, additionally containing agents that increase viscosity, surfactants, stabilizing agents, preservatives, corrigentov, fragrances, sweeteners, bioadhesive agents, co-solvents.

3. The composition according to claim 2, additionally containing derivatives of cellulose, polymers or copolymers of acrylic or methacrylic acid, ethylene or propylene glycols, polyethoxysiloxane hydrogenated castor oil, ethylenediaminetetraacetic acid (EDTA), sodium benzoate, sodium sorbate or potassium, dextrins, saccharin sodium, aspartame.

4. Composition according to any one of claims 1 to 3, additionally containing other active ingredients with complementary or any other useful activity.

5. The composition according to claim 4, containing antibacterial agents/disinfectants, antifungal agents, analgesics, anti-inflammatory agents, emollients, local analgesics.

6. A method of manufacturing a pharmaceutical composition according to any one of claims 1 to 5, comprising mixing hyaluronic acid, glycyrrhetic acid and polyvinylpyrrolidone with excipients and adjuvants suitable on the I local injection.



 

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