RU2328303C2 - Resorpted tablet based on mucus-producing medicinal plants and applied for mouth and pharynx inflammatory diseases - Google Patents

Abstract

FIELD: medicine; pharmacology.

SUBSTANCE: pharmaceutical formulation as solid dosage form for local treatment of mouth and pharynx inflammatory diseases, containing at least one mucus-producing medicinal plant as dry extract and at least one local analgesic taken in specified ratio. Application of pharmaceutical formulation described above for local treatment of painful inflammatory diseases of mouth cavity and pharynx.

EFFECT: composition is effective for local treatment of painful inflammatory diseases of mouth cavity and pharynx.

9 cl, 4 tbl

Description

The present invention relates to a pharmaceutical composition in the form of a solid dosage form, in particular in the form of a lozenges, containing a combination of at least one mucus-producing medicinal plant (mucous medicinal plant material) and / or its extract, especially Icelandic moss (Lichen islandicus) and / or the pharmacy moth (Althaea officinalis L.), and at least one local anesthetic.

The invention also relates to the use of the aforementioned pharmaceutical composition, respectively, a combination of at least one mucus-producing medicinal plant and / or its extract and at least one local anesthetic for the treatment of primarily inflammatory diseases of the oral cavity and pharynx associated with pain.

Inflammatory diseases of the oral cavity and pharynx, i.e. inflammation in the mouth and throat / pharynx often occur as a phenomenon associated with colds and acute respiratory infections, but also in the form of independent diseases. Such inflammatory processes in the oral cavity and pharynx are often accompanied by unpleasant pain sensations that occur in people suffering from such inflammations. Examples of such inflammatory diseases of the throat and pharynx that are not limiting the scope of the invention include inflammation of the throat, primarily sore throat, inflammation of the larynx (laryngitis), inflammation of the pharyngeal mucosa (pharyngitis) and inflammation of the pharyngeal (palatine) tonsils (tonsillitis). Such diseases of the throat / pharynx are often accompanied by pain when swallowing. Pain is often accompanied by inflammation in the oral cavity, such as, for example, stomatitis, gingivitis, damage to the oral mucosa and similar diseases. Further detailed information on these diseases can be found, for example, in Roche-Lexikon Medizin, 3rd ed., 1993, published by Urban & Schwarzenberg, München / Wien / Baltimore, as well as in Pschyrembel Medizinisches Wörterbuch, 257th ed. 1993, Nikol Verlagsgesellschaft mbH, Hamburg. In accordance with this, the concept of “inflammatory diseases of the oral cavity and pharynx” should be interpreted in the broadest sense and cover all inflammatory diseases that can occur in the oral cavity, pharynx, and throat.

Treatment of inflammatory diseases of the oral cavity and pharynx, depending on their severity, as a whole consists in local therapy, and in some cases when the disease progresses in a more severe form, in additional systemic therapy. If in a more severe form of the course of the disease the patient is systemically prescribed antibiotics, then under maintenance conditions and for milder forms of the course of the disease, under certain conditions, they are often limited only to local, symptomatic treatment with antiseptic drugs and inflammation-inhibiting substances (for example, antiflogists with anti-inflammatory action by means of local antibiotics, etc.), which can be used, for example, in the form of preparations for rinsing I spray (aerosol) or lozenge.

First of all, 1-hexadecylpyridinium chloride (the international non-proprietary name "cetylpyridinium chloride" (CPC)) has proven itself as an active substance for the local treatment of inflammatory processes in the oral cavity and pharynx. This is a quaternary ammonium compound having a bactericidal and fungicidal effect, which, among other things, is used in the form of lozenges. The inherent disadvantage of this active substance is that its use in high dosage and excessive use of preparations containing it can lead to problems in the gastrointestinal tract, shortness of breath, and excessive formation of methemoglobin, especially in children.

In addition, 1,3-bis (2-ethylhexyl) hexahydro-5-methyl-5-pyridinamine (the international non-proprietary name "hexetidine") has proven itself as a local antiseptic, respectively, as a means of disinfecting the mucous membrane of the oral cavity, throat and pharynx. ), which can be used, for example, in the form of a spray (aerosol) or solutions for gargling. However, with prolonged use of this active substance and with its use in high dosages, in this case, problems may also arise in the gastrointestinal tract, as well as painful sensitivity of the taste organs.

In addition to the above, active ingredients of natural origin are also used, for example, mucus-producing medicinal plants (the so-called mucous medicinal plant material) or their extracts, such as Icelandic moss (Lichen islandicus). However, such drugs do not always allow to achieve the proper therapeutic effect. This is primarily due to the fact that such drugs as a whole do not have any effect on pain symptoms in inflammatory diseases of the oral cavity and pharynx.

Based on the foregoing, the present invention was based on the task of proposing a pharmaceutical composition that would be suitable for effective topical treatment of primarily inflammatory diseases of the oral cavity and pharynx associated with pain (i.e., inflammatory diseases of the throat / pharynx and oral cavity) and which First of all, it would allow at least almost completely eliminate the above disadvantages inherent in the prior art, or at least mitigate their manifestation.

According to the invention, it was unexpectedly found that the above problem can be solved by a pharmaceutical composition in the form of a solid dosage form based on at least one mucus-producing medicinal plant and / or its extract (e.g., based on Icelandic moss (Lichen islandicus) or marshmallow pharmacy ( Althaea officinalis L.)) in combination with at least one topical anesthetic (e.g., benzocaine). Such a pharmaceutical composition is suitable primarily for the manufacture of lozenges, primarily based on hard candy, the local application of which allows to achieve a positive therapeutic effect in painful, respectively accompanied by pain, inflammatory diseases of the oral cavity and pharynx.

In accordance with this object of the present invention is a pharmaceutical composition in the form of a solid dosage form, which is suitable for topical treatment, especially accompanied by pain, respectively painful inflammatory diseases of the oral cavity and pharynx, and which contains in combination pharmaceutically effective amounts

(a) at least one mucus-producing medicinal plant and / or its extract, and

(b) at least one topical anesthetic. The above combination is primarily suitable for the temporary sole or supportive treatment of painful inflammation of the oral cavity and pharynx, since it, on the one hand, has an inhibitory and accordingly attenuating effect on inflammation, and on the other hand, has an effective analgesic effect. The use of a natural active substance from at least one mucus-producing medicinal plant and / or its extract (for example, Icelandic moss or marshmallow pharmacy) can effectively avoid side effects that occur when using synthetic active substances, for example cetylpyridinium chloride and hexetidine.

The terms "pharmaceutical composition", respectively, "pharmaceutical combination", which in the description of the present invention are mostly synonymous, should be interpreted in the broadest sense and encompass pharmaceutical compositions or combinations of any possible type, especially drugs, respectively drugs as such, as well as medical products, homeopathic remedies, etc.

The pharmaceutical composition according to the invention can be used, for example, in case of irritation of the mucous membrane accompanied by sore throat, pain in the throat due to drying out of the mucous membrane, or dry mucous membrane of the pharynx accompanied by sore throat. In addition, the pharmaceutical composition proposed in the invention, respectively, the combination can be used to eliminate sore throat while protecting its mucous membrane. The combination proposed in the invention allows to achieve a double effect: on the one hand, high efficiency in eliminating sore throats as such is achieved, and on the other hand, sufficient moistening of the mucous membrane is ensured and due to this, a feeling of dry mouth and the spread of bacteria are prevented. Thus, the pharmaceutical composition proposed in the invention, respectively, the combination allows you to actively counteract sore throat and dry mouth and fight inflammation just as effectively. Accordingly, the pharmaceutical composition according to the invention is suitable, for example, for maintenance therapy or monotherapy of mucosal irritation, accompanied by sore throat. In this way, it is possible to effectively deal with sore throat with the achievement of a double action, namely, to effectively suppress the inflammatory process, firstly, and effectively act on pain symptoms, and secondly. In addition, the hydration of the dried mucous membrane of the mouth complicates the further penetration of pathogens. In addition, the use of the composition of the invention provides the possibility of painless regeneration of surface-anesthetized areas that have changed as a result of inflammatory processes of the oral mucosa and thereby its healing. Thus, two effective effects are manifested, one of which consists in superficial anesthesia, and the other in weakening the inflammatory process.

According to the invention, it was unexpectedly found that the effect achieved by using the combination according to the invention of at least one mucus-producing medicinal plant, or an extract thereof (e.g., Icelandic moss and / or pharmacy moth) and at least one local anesthetic (e.g. benzocaine) and consisting in a significant reduction in irritation of the mucous membrane of the mouth and pharynx, exceeds the total effect from the use of each of these components separately. The foregoing indicates the presence of a combination of a synergistic effect according to the invention.

In accordance with the present invention, a plurality of mucus-producing medicinal plants or extracts thereof can be used in the composition according to the invention. The mucus-producing medicinal plants from the group comprising Icelandic moss (Lichen islandicus), marshmallow pharmacy (Althaea officinalis L.), plantain lanceolate (Plantago lanceolata L.), and mallow (Malva sylvestris L.) are particularly suitable for use in the pharmaceutical composition of the invention; and M. neglecta WALLR.), hay fenugreek (Trigonella foenum-graecum L.), dwarf orchis and quince (Cydonia oblonga MILL.). Icelandic moss (Lichen islandicus) and / or marshmallow pharmacy (Althaea officinalis L.), which can be used either individually or in combination with each other, are preferred according to the invention. Also preferred according to the invention is a combination of Icelandic moss (Lichen islandicus) or pharmacy marshmallow (Althaea officinalis L.), respectively, extracts of each of them and at least one of the other mucus-producing medicinal plants mentioned above, or extracts thereof. The use of these two medicinal plants is preferable for the reason that both of them allow to obtain the best results according to the invention.

As such, individual mucus-producing medicinal plants, respectively, their extracts are quite well known to specialists in this field.

Due to their anti-inflammatory properties, medicinal plants that produce mucus are used externally for the treatment of boils, abscesses, swollen lymph glands and inflammation of the pharynx, as well as orally as laxatives and fixing agents and for the treatment of gastritis and inflammation of the intestines.

Slimes are heteropolysaccharides with a molecular weight of from about 50,000 to 2,000,000, extracted from medicinal plant materials with hot or cold water. Highly viscous solutions formed by mucus, unlike resins, are not sticky. There are acidic and neutral mucus. Slimes, depending on their sugars, are divided into glucomannans or mannans, galactomannans, xylans or rhamnogalacturonans. Mucus, depending on their location in plants, can be further divided into vacuolar and membrane. As a prototype of acidic plant mucus, mucus of the marshmallow root of a pharmacy can be considered. Such mucus contains L-ramnose, D-galactose, D-galacturonic acid and D-glucuronic acid in a molar ratio of about 3: 2: 3: 3. The polysaccharide part having the simplest structure is constructed of repeating undecasaccharide blocks.

Icelandic moss, in contrast to the accepted interpretation of the term "moss", is called lichen Lichen islandicus or Cetraria islandica (Parmeliaceae), exported from northern countries, such as Iceland, Norway and Sweden. In essence, Icelandic moss is a tall-dried lichen of Cetraria islandica, as well as its preparations. This medicinal plant contains, in particular, mucous substances and bitterness, as well as bitter tasting lichen acids. Powdered lichen, when boiled in a highly diluted solution of sodium bicarbonate, dissolves by about 60 wt.%, And upon cooling the resulting solution a gelatinous mass forms. The extract consists of a mixture of polysaccharides - lichenin and isolechenin, a number of bitter lichen acids (fumaroprotocetrora, protocetrora and cetrara acids), as well as protolychesteric acid, which is converted into lychesteric acid during processing and usnic acid as an antibiotic. As a mucus-producing medicinal plant, Icelandic moss has irritating properties and an antimicrobial effect. The presence of bitterness in Icelandic moss is due to its use in the absence of appetite. Icelandic moss is used, for example, for catarrh and diarrhea, as a bitter tonic, externally for poorly healing wounds, as part of cosmetic preparations, in hair fixers, as an additive to biscuit flour and similar materials, for anorexia, as well as for irritations oral mucosa and pharynx. An Icelandic moss based disinfectant for oral and pharyngeal disinfection alleviates respiratory irritation causing a dry cough. Macerates obtained by cold soaking of Icelandic moss, and other bitter-tasting preparations of this medicinal plant are used to eliminate low or high acidity. As an example of dosage forms based on a crushed medicinal plant, infusions, as well as other galenical preparations, respectively macerates, obtained preferably by cold soaking of the crushed medicinal plant, and other preparations intended for oral administration with bitter taste can be called, depending on its purpose. More detailed information about Icelandic moss can be found, for example, in the following literature: Römpp Chemie-Lexikon, 9th ed., Vol. 3, publisher Georg Thieme Verlag, Stuttgart / New York, 1990, c.2055-2056 , keyword "Islandisches Moos"; HagerROM 2001, Springer Verlag, Heidelberg, keywords "Cetraria", "Cetraria ericetorum OPIZ", "Cetraria islandica (L.) ACHARIUS", "Lichen islandicus (Islandisches Moos)"; monograph "Lichen islandicus (Islandisches Moos)", Bundesanzeiger No. 43 of March 2, 1989; H. Wagner, "Pharmazeutische Biologic - Drogen und ihre Inhaltsstoffe", Gustav Fischer Verlag, Stuttgart / New York, 1985, p. 281, keyword "Cetrariae Lichen (Lichen islandicus - Isländisches Moos)".

Marshmallow pharmacy (Althaea officinalis L.), used in the form of its root, leaves and flowers, grows on saline moist soils in Central, Eastern and Southern Europe. The lateral and subordinate roots of the marshmallow, collected in the fall, after they are separated from the woody main root and removed the root lobes and cortical layers and after drying at 35 ° C, go on sale in a peeled or unpeeled form. The brownish color of the medicinal plant peeled from the bark indicates a deterioration in its quality, while its subsequent “revitalization” with a sulfite solution is not allowed. In addition to the roots of the pharmacy moth, its dried three-five-lobed leaves, about 10 cm long and about 8 cm long, covered with gray hairs, collected before or during flowering, are also used, as well as dried flesh-colored petals collected in July / August. Marshmallow pharmacy is a seed-propagating or vegetatively herbaceous perennial about 1 m high. The content of mucous substances in the roots of this plant collected in late autumn reaches 15%. In early spring and summer, the content of mucous substances in the root of the marshmallow is about 5-6%. The content of mucous substances in the leaves and flowers of the marshmallow is from 6 to 9%. The mucus is localized in the root in certain mucous cells of the cortical parenchyma and pleurenchyma. This mucus consists of galacturonoramnanes, glucans and arabinogalactans. Water extracts from the roots should be obtained by soaking them (maceration) at room temperature to avoid unwanted swelling of the starch contained in them in large quantities. Marshmallow pharmacy is used as a medicinal plant material for making tea or for making Sirupus Althaeae syrups. Such drugs are mainly used for inflammatory irritative conditions in the pharyngeal cavity. Outwardly, the pharmacy marshmallows are used as part of softening compresses and baths, as well as in the form of poultices.

Plantain lanceolate (Plantago lanceolata L.) is distributed throughout Europe, as well as in North and Central Asia. This medicinal plant comes from plants and crops that are wild-growing mainly in Southeast Europe. It is possible to use dried lanceolate leaf blades from olive to brown in color with about three to seven parallel veins. As an appropriate medicinal plant material, dried leaves, stems and whole flowers of this plant can be used. Along with mucus, plantain lanceolate contains tannins as other ingredients, iridoid glycoside aucubin (from 1.9 to 2.4%), which causes the dark color of an insufficiently thoroughly dried plant and is used for its identification verification, as well as mustard oil sulforaphane. Plantain lanceolate, primarily its leaves, are used mainly in teas and syrups for inflammation of the oral cavity and pharynx.

Mallow (Malva sylvestris L. and M.neglecta WALLR.), Used primarily in the form of its flowers and leaves, lives in Europe, Asia Minor, the Mediterranean and Western India. The pink-violet flowers collected during the flowering period find practical use, respectively, folded castings, which are greatly wrinkled as a result of drying, are sold predominantly in packaged form. Mallow is a two- or perennial herbaceous plant. Its flowers and leaves contain from 6 to 8% of mucous substances. As a result of hydrolysis of mucus contained in mallow, glucose, arabinose, ramnose and galactose are obtained. Mallow flowers are used as part of gargles and baths, and together with leaves as an expectorant in precast teas.

Hay fenugreek (Trigonella foenum-graecum L.), used mainly in the form of its seeds, grows throughout the Mediterranean, as well as in Eastern Europe, India and China. This medicinal plant material is mainly imported from India and Morocco. Brownish-red rectangular and diamond-shaped flattened exceptionally hard seeds with a length of about 5 mm and a width of about 3 mm, on the surface of which there is a groove, find practical application. Along with fatty oil, hay fenugreek contains from 20 to 30% mucus, trigonellin, nicotinic acid amide, choline, bitterness and saponin. Mucus is secreted from powdered seeds. The powder of hay fenugreek seeds is used externally as a part of compresses for boils, abscesses and swollen lymph glands and inside as an expectorant and restorative.

Dremlik orchis, used mainly in the form of its Salep (dried tubers), comes from orchids of various species, primarily Orchis mascula L., Orchis morio L., Orchis militaris L., Anacamptis pyramidalis L. RICH. and Platanthera bifolia L. RICH. Wrinkled hard brownish tubers with a length of about 4 cm and a thickness of about 3 cm are used in practice, after which the basket layer is removed after collection and which is first poured with boiling water and then dried by artificial heating. The mucilage of the Orthis-Dremlik containing up to 50% predominantly glucomannan, respectively glucan, is used mainly in pediatrics as a fixing agent.

The homeland of quince (Cydonia oblonga MILL.) Is the southeastern part of the Arabian Peninsula. The main importers of this medicinal plant material are Spain, Portugal and Iran. Ripe dried red-brown seeds of quince false fruits, which have a slightly flattened shape, find practical application. Outside, the seeds are partially covered with a dried crust of mucus and are often glued together. Quince seeds have a slightly pronounced aftertaste of bitter almonds. The epidermis of seeds contains about 22% of the mucus, the predominant part of which is soluble in water. The sugar components of mucus are arabinose, xylose, and partially methylated uronic acid. This medicinal plant material is used only in unmilled form. Quince mucus is used externally as a part of ointments or creams for cracked lips and nipples of the mammary glands, as well as for burns and pressure sores.

According to the invention, the best results are obtained using Icelandic moss and / or marshmallow pharmacy when used individually and in combination with each other. Not based on any particular theory, it is believed that the particularly high effect of the pharmacy moth is probably due to the acidic mucus of this plant.

For more information on mucus-producing medicinal plants and their preparations, as well as their effects and their applications, see H. Wagner, Pharmazeutische Biologie - Drogen und ihre Inhaltsstoffe, Gustav Fischer Verlag, Stuttgart / New York, 1985, primarily c.280 onwards.

As regards the mucus-producing medicinal plant used according to the invention, in accordance with the invention it can be used in the pharmaceutical composition, respectively, in the form of the plant itself, especially in the form of its crushed, including powder, parts.

In addition to this, it is also possible to use a mucus-producing medicinal plant in the form of its extract, especially a dry extract. Such a dry plant extract is preferably obtained starting from an aqueous, alcoholic or aqueous-alcoholic extract, preferably an aqueous extract (for example, obtained by the usual method, in particular by removing water and / or alcohol from it in a vacuum, optionally by heating, lyophilization, etc. .). In this case, the ratio between the medicinal plant material and the extract can vary widely. When using a mucilage-producing medicinal plant in the form of its extract, the ratio between the medicinal plant material and the extract should be primarily from 0.4: 1 to 15: 1, preferably from 1: 1 to 10: 1, preferably from 5: 1 to 8: one.

An important advantage of using the extract of the mucus-producing medicinal plant over the use of the medicinal plant as such is the ability to use the mucus-producing medicinal plant in high concentrations, which ensures a particularly high therapeutic effect. An optimal therapeutic effect is achieved by using a mucus-producing medicinal plant in the form of an extract thereof, preferably a dry extract, with a ratio between the medicinal plant material and the extract of at least 1: 1 or more.

The content of the mucus-producing drug (s) of the plant (s) and / or its (s) extract (s) in the pharmaceutical composition according to the invention, respectively, of the combination can vary widely. In general, the content of the mucus-producing medicinal plant (s) and / or its extract (s) should be from 0.5 to 20 wt.%, Primarily from 1 to 10 wt.%, in terms of the pharmaceutical composition, respectively, combination, i.e. in terms of solid dosage form. However, depending on the intended use of the pharmaceutical composition of the invention, it may be preferable or it may be necessary to use the mucus-producing medicinal plant (s) and / or its extract (s) in amounts different from the above values in one direction or another.

As a local anesthetic according to the invention, in principle, any suitable local anesthetic can be used.

Local anesthetics reversibly and locally suppress the excitability of transmitting pain impulses of the terminal apparatus of the sensory nerves and block the conduction of impulses along sensitive nerve fibers. As a result, without loss of consciousness, the feeling of pain is temporarily eliminated. The action of local anesthetics on sensory nerve endings is not specific, and structures with different excitability have, obviously, different sensitivity. So, for example, when local anesthetics are used in usual dosages, the motor functions do not "turn off" mainly because the motor nerve fibers have a larger diameter compared to the sensory nerve fibers, which play an important role in conducting pain impulses. More detailed information on local anesthetics can be found, for example, from E. Mutschler et al., "Mutschler Arzneimittelwirkungen - Lehrbuch der Pharmakologie und Toxikologie", 8th ed., Wissenschaftliche Verlagsgesellschaft mbH Stuttgart, 2001, c. 267 ff. ; Römpp Chemie-Lexikon, 10th ed., Vol. 3, publisher Georg Thieme Verlag, Stuttgart / New York, 1997, p. 2442, the keyword "Lokalanästhetika" and in the literature cited in these publications.

As an example of local anesthetics suitable for use for the purposes of the invention, local anesthetics based on esters or amides of organic acids can be mentioned. A local ether type anesthetic is preferred. Examples of such local ether-type anesthetics are benzocaine (its etoform), procaine and tetracaine. As an example of local amide type anesthetics, lidocaine, ethidocaine, prilocaine, mepivacaine, bupivacaine, S-ropivacaine and articaine are primarily mentioned.

Benzocaine is most preferably used as a local anesthetic in the pharmaceutical composition of the invention. The use of benzocaine is preferable for the reason that, as was unexpectedly found according to the invention, benzocaine when used in the pharmaceutical composition of the invention, respectively, in combination with the mucus-producing medicinal plant (s) exhibits the best act. Not based on any particular theory, it is believed that the particularly high efficiency of benzocaine, which is a neutral non-ionizable primary amine, is likely due to the fact that the blockade of excitation caused by benzocaine is based on the disintegration of the normal membrane structure due to the introduction of benzocaine into the lipid phase, which indirectly leads to blockade of the sodium channel, i.e. this mechanism of action differs from the mechanism of action of other local anesthetics of the classical type (for example, based on secondary or tertiary amines). Such a mechanism of action of benzocaine, which is different from classical anesthetics, is important insofar as the pH value of the inflamed tissue due to local lactate acidosis is reduced compared to the pH value of normal (healthy) tissue. Under such conditions, classical local anesthetics based on secondary or tertiary amines are present in the aqueous phase at pH 7.4 or less, mostly in the ionized state, as a result of which the permeability of such anesthetics is reduced, and unlike non-ionizable benzocaine, they can lose their anesthetic effect. Therefore, a pharmaceutical combination of at least one mucus-producing medicinal plant (for example, marshmallow pharmacy and / or Icelandic moss), especially its extract, and benzocaine is most preferred. However, a combination of at least one mucus-producing medicinal plant, especially its extract, and other local anesthetics also has an effective spectrum of action.

The content of a local anesthetic in a pharmaceutical composition can vary widely. In the General case, it is from 0.05 to 2 wt.%, Especially from 0.1 to 1 wt.%, Preferably from 0.2 to 0.6 wt.%, In terms of the pharmaceutical composition, respectively, the combination. However, depending on the intended use of the pharmaceutical composition of the invention, it may be preferable or it may be necessary to use local anesthetic (s) in amounts different from the above values in one direction or another.

Along with the aforementioned active substances and ingredients, the pharmaceutical composition according to the invention may also contain other active substances and / or ingredients, for example, processing aids, flavorings, taste enhancers, sweeteners and sweeteners, acidifiers, stabilizers and / or antiseptics.

In general, the pharmaceutical composition according to the invention contains the active substances and / or ingredients embedded in a solid matrix, respectively, a mass. In other words, the active substances and / or ingredients are included, respectively, embedded in the matrix and due to this are effectively protected and homogeneously distributed.

The solid dosage form and the introduction, respectively, the inclusion of active substances and / or ingredients in a solid matrix, respectively, the mass provides the achievement of a number of the following advantages. Firstly, this approach allows you to more effectively dose the active substances and / or ingredients, i.e. provides higher accuracy of their dispensing. Secondly, thanks to this approach, it is possible to improve the possibilities of using, respectively, taking the appropriate drugs, i.e. the patient can take them almost regardless of their location (for example, on a trip, outdoors, etc.), since it does not require the preparation of special dosage forms. In addition, the decisive advantage of solid dosage forms is that the inclusion of active substances in their composition can generally increase the stability of the latter during storage. In addition, a solid dosage form provides the active substance in the oral cavity and pharynx for a certain period of time and thereby provides effective treatment. In addition to this, a solid dosage form, primarily due to the incorporation of the active substances and / or ingredients into the matrix, helps to improve their compatibility with other active substances and their uniform, homogeneous distribution in the matrix.

For use as a matrix, respectively, of a mass intended for incorporation into it of active substances and / or ingredients, sugars of any type and / or sugar substitutes of any type are particularly suitable. Examples of sugars suitable for use in the inventive purposes include sucrose, glucose, especially dextrose, and fructose. Sugar substitutes according to the invention are selected primarily from the group of so-called sugar alcohols. Preferred sugar substitutes according to the invention are selected from the group consisting of mannitol, xylitol, sorbitol, isomalt, maltitol syrup, lactitol, leukemia, fructooligosaccharides, glucans and polyglucose, most preferably isomalt.

If sugars and sweet substances are collectively called sweeteners, then sugar substitutes, unlike sweet substances with a pronounced, intense taste, are used from a technological point of view similarly, for example, to sucrose, i.e. they have a "base" and physiological energy value (they are the so-called "nutritious sugar substitutes"). Sugar substitutes in terms of their sweetness over a wide range approximately correspond to sucrose. The physiological advantage of sugar substitutes over sucrose is their insulin-independent metabolism (which is preferable for patients with diabetes) and a partially reduced cariogenic effect. Some sugar substitutes (e.g. xylitol) are known to have anticariesogenic effects.

The term "sugar alcohol" is used as a collective designation for polyhydroxy compounds that are formed from monosaccharides as a result of the reduction of the carbonyl group and which, although they are not sugars, nevertheless have an equally sweet taste and can therefore be used as sugar substitutes under certain conditions. Depending on the amount of hydroxyl groups contained in the molecule of these generally crystalline, water-soluble polyols, so-called tetrites, pentites, hexites, etc. are distinguished. Examples of naturally occurring sugar alcohols include glycerin, threitol, erythritol, adonite (ribite), arabitol (formerly called lixitol) and xylitol, as well as dulcite (galactite), mannitol and sorbitol (glucite).

Further information regarding sugar, sugar substitutes and sugar alcohols can be found, for example, in Römpp Chemie-Lexikon, 10th ed., Vol. 6, Georg Thieme Verlag, Stuttgart / New York 1999, pp. 5096-5100, the keywords "Zucker", "Zuckeralkohole" and "Zuckeraustauschstoffe".

The content of the matrix, respectively, solid mass, especially sugars and / or sugar substitutes, in the pharmaceutical composition of the invention can vary within wide limits. The amount of matrix mass (i.e. sugars and / or sugar substitutes) generally ranges from 80 to 99.45 wt.%, Especially from 85 to 99 wt.%, Preferably from 90 to 99 wt.%, In terms of on the pharmaceutical composition. Nevertheless, depending on the purpose of the pharmaceutical composition proposed in the invention, respectively, depending on the specific situation, under certain conditions it may be preferable or it may be necessary to use a matrix or solid mass in quantities that differ from the above values in one direction or another.

According to a particularly preferred embodiment of the present invention, a pharmaceutical composition or a solid dosage form is provided in the form of a lozenge tablet, especially in the form of hard candy. If the solid dosage form according to the invention is presented in the form of a lozenges, then when a patient takes it and dissolves from it into the oral cavity and pharynx, a therapeutically effective amount of active substances and / or ingredients is released. The best therapeutic results were obtained in the treatment of inflammatory diseases of the oral cavity and pharynx accompanied by pain with resorption tablets, preferably on the basis of hard caramel containing Icelandic moss (Lichen islandicus) and / or marshmallow pharmacy (Althaea officinalis L.) or their extracts in combination with benzocaine.

In a preferred embodiment, proposed in the invention pharmaceutical composition, presented in the form of tablets for resorption, primarily based on hard candy, the mass of such tablets can vary within wide limits. In general, the total weight of the lozenges is from 1 to 5 g, preferably from 2 to 3 g, particularly preferably from 2.4 to 2.7 g, with the content in each lozenges of the drug producing the mucus (s) ) plants (s) (for example, Lichen islandicus and / or Althaea officinalis L., respectively, of their extracts) in an amount of from 13 to 260 mg, in particular from 26 to 130 mg, in combination with a local anesthetic, preferably benzocaine, in an amount from 1.3 to 52 mg, especially from 2.6 to 26 mg, preferably from 5.2 to 15 mg, incorporated into the mass, respectively a matrix (primarily sugar and / or sugar substitute), the amount of which is from 1.9 to 4.9 g, primarily from 2 to 2.6 g. In addition, the resorption tablet according to the invention may, as indicated above, contain other active substances and / or ingredients, for example, other mucus-producing medicinal plants and / or extracts thereof, processing aids, flavoring agents, sweeteners and sweeteners, acidifiers, stabilizers and / or antiseptics. In this regard, reference may be made to the embodiments of the invention described above.

Proposed in the invention, the pharmaceutical composition is prepared according to known technology. More detailed information on the manufacturing technology of the pharmaceutical composition is given in the examples of the invention described below. One of the possible methods for the manufacture of lozenges on the basis of hard candy is, for example, that first, weighing the necessary portions of active ingredients and ingredients, optionally after grinding them, and then they are mixed with the basic substance based on sugars or their substitutes, for example, isomalt, after which the main substance is heated and tablets are formed from it for resorption, which are finally cooled. Such a technology for the manufacture of lozenges as such is well known to those skilled in the art and therefore is not discussed in more detail in the present description.

The object of the present invention is the further use of the pharmaceutical composition as described above for topical treatment of inflammatory diseases of the oral cavity and pharynx associated with pain, respectively, for the manufacture of a medicament intended for local treatment of inflammatory diseases of the oral cavity and pharynx primarily associated with pain.

Another object of the present invention is the use of the combination described above of at least one mucus-producing medicinal plant and / or its extract and at least one local anesthetic for topical treatment of primarily inflammatory diseases of the oral cavity and pharynx associated with pain, respectively, for the manufacture of a medicament , intended for local treatment, primarily accompanied by pain of inflammatory diseases of the oral cavity and pharynx.

With respect to the remaining details regarding the use according to the invention, reference can be made to the above explanations which relate to the pharmaceutical composition according to the invention, respectively to the combination, and which respectively apply to its use according to the invention.

Other embodiments and modifications of the invention, as well as its advantages without further explanation, are obvious to specialists in this field from the text of the present description and allow the possibility of their practical implementation without going beyond the scope of the invention.

Below the present invention is illustrated by examples of its implementation, which are purely illustrative and do not limit its scope.

Examples of carrying out the invention

1. Examples for the manufacture of pharmaceutical compositions

The manufacture of the pharmaceutical compositions of the invention in the form of lozenges (based on hard candy) based on an extract of various mucus-producing medicinal plants (Lichen islandicus, Althaea officinalis L., as well as Lichen islandicus + Althaea officinalis L.) in combination with varying amounts of benzocaine quantities

Various pharmaceutical compositions are prepared in the form of lozenges based on hard candy. Fructose and / or glucose syrup can be used as the basis for lozenges, respectively of hard candy base (matrix) in the manufacture of sugar-containing tablets, and in the manufacture of sugar-free tablets, sugar substitutes, especially sugar alcohols, preferably maltitol or isomalt (Palatinit ^® ) , in both cases, i.e. and sugar-containing tablets and sugar-free tablets can, if necessary, include sweeteners in varying amounts (for example, acesulfame, aspartame, cyclamate, saccharin, thaumatin or neohesperidin). Appropriate active substances and / or ingredients are incorporated into the matrix. Tablets for resorption, respectively hard caramel are made by a known method.

To this end, in accordance with the formulation of a particular tablet for resorption by weighing, the necessary portions of the starting material are measured and individually mixed with the main substance / hard-caramel base (for example, isomaltite). You can not add water. The mixing process is carried out on a weighing device with appropriate unlocked calibrated scales. The raw materials are heated, processed on the production line and crushed into small portions. To these portions, then through a separate dispenser add the starting materials, respectively, intermediate products, especially

- Icelandic moss (Lichen islandicus) and / or marshmallow pharmacy (Althaea officinalis L.),

- benzocaine (local anesthetic),

- optional spice-flavorings,

- optionally peppermint oil and

- optionally tartaric acid (as a stabilizer / acidifier).

After this, individual portions are again mixed together and the entire batch is mixed. Next, the batch is sent for intermediate storage in the appropriate drive, from where it is fed back to the dosing machine or dispenser. At this position, tablets are made for resorption of the appropriate size, weighing them during this process. Finished tablets are immediately sent to the machine for packaging in blister packs, where they are packaged in an open packaging material. After that, at the end of the blister packaging process, the finished product is placed on pallets. Next, the finished product is sent to quarantine, its quality is monitored for compliance with the content of active ingredients in the tablets, respectively the ingredients and their mass, with the specified parameters and, after appropriate checks, they are allowed to be sold through the distribution network. In this way, for example, sugar-free resorption tablets (“hard caramel”) are made with a variable content of local anesthetic (benzocaine) (0.2 to 0.6 wt.% Based on the weight of the tablet for resorption) specified in the following composition tables (first series of lozenges).

Table 1 Icelandic moss (Lichen islandicus) in combination with 0.2 wt.% Benzocaine (lozenges without sugar) Raw materials The content of dry components in one tablet for resorption, mg The consumption of dry components in kg per 1000 kg Palatinit ^® M (isomaltitis) 2503,000 962,808 Water 0,000 0,000 Lichen islandicus (extract, ratio between medicinal plant and extract 7: 1) 50,000 19,231 Spice flavoring 26,000 10,000 Peppermint Oil 0,500 0.192 Benzocaine 5,200 2,000 Wine acid 15,000 5,769 Total: 2,600,000 1,000,000

table 2 Icelandic moss (Lichen islandicus) in combination with 0.3 wt.% Benzocaine (sugar-free lozenges) Raw materials The content of dry components in one tablet for resorption, mg The consumption of dry components in kg per 1000 kg Palatinit ^® M (isomaltitis) 2500,700 961,808 Water 0,000 0,000 Lichen islandicus (extract, ratio between medicinal plant and extract 7: 1) 50,000 19,231 Spice flavoring 26,000 10,000 Peppermint Oil 0,500 0.192 Benzocaine 7,800 3,000 Wine acid 15,000 5,769 Total: 2,600,000 1,000,000

Table 3 Icelandic moss (Lichen islandicus) in combination with 0.4 wt.% Benzocaine (lozenges without sugar) Raw materials The content of dry components in one tablet for resorption, mg The consumption of dry components in kg per 1000 kg Palatinit ^® M (isomaltitis) 2498,100 960,808 Water 0,000 0,000 Lichen islandicus (extract, ratio between medicinal plant and extract 7: 1) 50,000 19,231 Spice flavoring 26,000 10,000 Peppermint Oil 0,500 0.192 Benzocaine 10,400 4,000 Wine acid 15,000 5,769 Total: 2,600,000 1,000,000

Table 4 Icelandic moss (Lichen islandicus) in combination with 0.5 wt.% Benzocaine (lozenges without sugar) Raw materials The content of dry components in one tablet for resorption, mg The consumption of dry components in kg per 1000 kg Palatinit ^® M (isomaltitis) 2495,500 959,808 Water 0,000 0,000 Lichen islandicus (extract, ratio between medicinal plant and extract 7: 1) 50,000 19,231 Spice flavoring 26,000 10,000 Peppermint Oil 0,500 0.192 Benzocaine 13,000 5,000 Wine acid 15,000 5,769 Total: 2,600,000 1,000,000

Table 5 Icelandic moss (Lichen islandicus) in combination with 0.6 wt.% Benzocaine (sugar-free lozenges) Raw materials The content of dry components in one tablet for resorption, mg The consumption of dry components in kg per 1000 kg Palatinit ^® M (isomaltitis) 2492,900 958,808 Water 0,000 0,000 Lichen islandicus (extract, ratio between medicinal plant and extract 7: 1) 50,000 19,231 Spice flavoring 26,000 10,000 Peppermint Oil 0,500 0.192 Benzocaine 15,600 6,000 Wine acid 15,000 5,769 Total: 2,600,000 1,000,000

Similarly to the first series of resorption tablets containing Lichen islandicus extract, a second series of resorption tablets with extract of Althaea officinalis L. and a third series of resorption tablets containing a mixture of extracts of Lichen islandicus and Althaea officinalis L. (in a 1: 1 ratio) were prepared, in each case with varying in the range from 0.2 to 0.6 wt.% the content of benzocaine.

2. Application examples

Twenty patients with colds caused by acute sore throat, accompanied by pain and difficulty swallowing, without additional systemic treatment, underwent only local therapy containing Icelandic moss (Lichen islandicus) tablets for resorption of the first series. Ten patients took the solid pharmaceutical composition of the invention based on hard candy with a 0.5 wt% benzocaine content, made in accordance with the above example (listed in Table 4), and the remaining ten patients took a commercially available drug (lozenges for resorption / chewing pastilles with gum arabic as a matrix) containing only Icelandic moss in a lower dosage (80 mg of water extract from Icelandic moss in the ratio between medicinal plant and ex Rakta 0.4-0.8: 1 in one lozenge) and does not contain a local anesthetic.

Both drugs showed an inhibitory effect on inflammation. However, in patients for the treatment of which the pharmaceutical composition according to the invention was used, due to the presence of a local anesthetic immediately after the use of the drug (its resorption), a significant pain relief was observed, while in patients who took a drug not corresponding to the invention, painful difficulties persisted when swallowing. In patients for the treatment of which the composition of the invention was used, due to the higher dosage of Icelandic moss and the higher efficiency of the dosage form, respectively, of the galenic preparation (with an isomalt matrix), after one or two days, a significant reduction in inflammation was observed, which completely disappeared already after five to eight days, while when using a drug not corresponding to the invention with a lower dosage of Icelandic moss and without a local anesthetic, the process is cured Niya lasted much longer. When using a composition not corresponding to the invention, the first signs of relief appeared only after about three to four days, and the residual symptoms disappeared only after more than ten days of treatment.

The results of the study described above indicate that the use of the pharmaceutical composition of the invention in the form of a double combination provides a much higher therapeutic effect compared to the dosage form that does not correspond to the invention, since the pharmaceutical composition of the invention allows, firstly, to more effectively eliminate pain symptomatology, and secondly, to achieve a therapeutic effect faster due to the higher content of drug asthenic component with a higher ratio between the medicinal plant and the extract.

Comparable results were obtained with the use of tablets for resorption of the second and third series.

In the treatment of painful acute tonsillitis, the pharmaceutical composition according to the invention provides extremely effective elimination of concomitant tonsillitis symptoms, namely pain and inflammatory symptoms. This is the decisive advantage of the combination according to the invention.

Claims (9)

1. A pharmaceutical composition in the form of a solid dosage form for topical treatment of inflammatory diseases of the oral cavity and pharynx, containing a combination of a) at least one mucus-producing medicinal plant in the form of a dry extract in an amount of from 0.5 to 20 wt.% in terms of the pharmaceutical composition. b) at least one local anesthetic in an amount of from 0.05 to 2 wt.% in terms of the pharmaceutical composition. 2. The pharmaceutical composition according to claim 1, in which the mucus-producing medicinal plant is selected from the group comprising the following mucus-producing medicinal plants and their combinations: Icelandic moss (Lichen islandicus), marshmallow pharmacy (Althaea officinalis Z.), plantain lanceolate (Plantago lanceolata L.), Mallow (Malva sylvestris L. and M. neglecta WALLR.), hay fenugreek (Trigonella foenum-graecum L.), dwarf orchis and quince (Cydonia oblonga MILL.), among which Icelandic moss (Lichen islandicus) and / or pharmacy marsh (Althaea officinalis L.) are preferred. 3. The pharmaceutical composition according to claim 1, which contains a mucus-producing medicinal plant in the form of a dry extract in an amount of from 1 to 10 wt.%, In terms of the pharmaceutical composition. 4. The pharmaceutical composition according to claim 1, in which the local anesthetic is a local anesthetic based on an ester or amide of an organic acid and is primarily selected from the group consisting of benzocaine, procaine, tetracaine, lidocaine, ethidocaine, prilocaine, mepivacaine, bupivacaine, S- ropivacaine and articaine, among which benzocaine is preferred. 5. The pharmaceutical composition according to claim 1, which contains a local anesthetic in an amount of from 0.1 to 1 wt.%, In terms of the pharmaceutical composition. 6. The pharmaceutical composition according to claim 1, wherein in the pharmaceutical composition the active substance and ingredients are contained in a solid matrix derived from sugars and / or sugar substitutes, the sugar being selected from the group consisting of sucrose, glucose and fructose, and the sugar substitute selected from sugar alcohols, preferably from the group consisting of mannitol, xylitol, sorbitol, isomalt, maltitol syrup, lactitol, leukemia, fructooligosaccharides, glucans and polyglucose, while sugar and / or sugar substitute is present in an amount o t 80 to 99.45 wt.% in terms of the pharmaceutical composition. 7. The pharmaceutical composition according to claim 1 in the form of a solid dosage form, which is a lozenge tablet, which, when taken and absorbed by the patient, releases a therapeutically effective amount of active substances and ingredients into the oral cavity and pharynx. 8. The pharmaceutical composition according to claim 7 in the form of a solid dosage form, which is a tablet for resorption, containing a solid extract of Lichen islandicus and / or Althaea officinalis L. in combination with benzocaine. 9. The use of the pharmaceutical composition according to claims 1-8 for local treatment of inflammatory diseases of the oral cavity and pharynx accompanied by pain.