Agent for treatment of sensitive skin, the composition based on it and the way of processing leather

 

(57) Abstract:

The invention relates to cosmetology, in particular to the agent for processing sensitive skin, to compositions containing an agent for treatment of sensitive skin, and also to a method for skin treatment. The use of CGRP antagonist in the composition containing a cosmetically, dermatologically or pharmaceutically suitable environment for processing sensitive skin, in particular for preventing and/or combating skin irritation, and/or herpes, and/or eritem, and/or dysesthesias feelings, and/or burning sensations, and/or skin itch, and/or itching on mucous membranes. The CGRP antagonist can influence the symptoms of neurogenic origin, resulting from an external agent is able to modify the biochemical and biophysical constants of skin tissues. 3 S. and 13 C.p. f-crystals.

The present invention relates to the application of antagonist CGRP (peptide derived gene calcitonin: Calcitonin Gene Related Peptide) in the cosmetic, pharmaceutical or dermatological compositions intended for topical application to sensitive skin, and also relates to cosmetic compositions containing CGRP antagonist for reducing the EU ETS, used in cosmetic, pharmaceutical or dermatological field.

It is known that the skin of some people more sensitive than the skin of other people. Symptoms of sensitive skin until now poorly understood, and the range of problems such as skin poorly defined; nobody knows the processes that cause skin sensitivity, skin Hyper reactivity of non-allergic nature. Some believe that sensitive skin is a skin which reacts to cosmetic substances, while others believe that we are talking about the skin, which responds to some external factors that are not associated significantly with cosmetic substances.

Conducted some research in order to try to determine the sensitivity of the skin, for example, tests were conducted with lactic acid and DMSO, which is known as irritant substances: see, for example, article K. Lammintausta and others, Dermatoses, 1988, 36, pages 45-49; article So Anger et J. Serup, Clinical and Experimental Dermatology, 1989, 14, pages 214-217. However, these tests are not allowed to be characteristic of sensitive skin.

Moreover, sensitive skin considered such as skin prone to allergies.

Because p is s carried out indirectly, for example, limiting the use in the cosmetic compositions of substances with irritating, for example, surfactants, preservatives or flavour components, as well as a number of active substances.

The applicant has carried out a large number of clinical studies and was able to determine the symptoms associated with sensitive skin. These symptoms are, in particular, subjective symptoms, which are primarily dysesthesias sensations. Under dysesthesias sensations understand more or less painful sensations experienced in the area of the skin, for example, tingling, goose bumps, itching or itchy, burning, inflammation, discomfort, twitching, etc.

The applicant was able to show, moreover, that sensitive skin is not a skin prone to allergies. In fact, skin prone to allergies, this is a skin that reacts to external agents - any allergen causing the allergic reaction. We are talking about the immunological process that develops only if there is an allergen and which affects only sencibilisiruet subjects. The main characteristic of sensitive skin, soglasno individual, even if these individuals with sensitive skin react more quickly than others. This mechanism is not immunological, he has specificeski character.

The applicant found that sensitive skin can be presented in a clinical understanding of the two forms, namely, the skin is capable of irritation, and/or reactive skin; and the skin, which is characterized by an intolerance.

The skin is capable of irritation, and/or reactive skin is a skin which reacts by the emergence of itching, i.e., by scratching or pricking on various factors such as the environment, emotions, foods, the wind, rubbing, shaving, soap, surfactants, hard water with high calcium concentration, temperature variations or wool. Basically, these signs will accompany dry skin, with or without a scab, or accompany the skin, which has erythema.

The skin, characterized by intolerance, is a skin which reacts by sensations of burning, twitching, the emergence of pins and needles and/or redness on various factors such as the environment, emotions, foods. In General, these signs are accompanied by Hyperboreans skin or acne problems skin imiola unambiguous clinical semiology: itching sensation, and/or tingling and/or burning generally develop under the influence of local factors, such as friction, soap, surfactants, hard water with a high calcium concentration, shampoos or lotions. These feelings can sometimes develop under the influence of such factors as the environment, emotions, and/or food. Erythema and Hyperborea skin of the scalp as well as dandruff, often accompany the above symptoms.

In addition, certain anatomical areas, for example, in large folds (inguinal areas, genital areas, axillary sites, my sites, anal area, the areas located under the breast, in the crease of the elbow area) and on the foot sensitive skin manifests itself in the form of itching sensations and/or dysesthesias sensations (heat, tingling), associated in particular with the presence of secretions, sweat, friction, contact with wool, surfactants, hard water with a high concentration of calcium and/or temperature changes.

In order to determine sensitive skin or not, the Applicant has developed the test. Indeed, having a large number of experiments aimed at predicame with sensitive skin and those who responds to topical application of capsaicin.

Test using capsaicin is applied to a skin area of about 4 cm20.05 ml of ointment containing 0.075% capsaicin, and check the appearance of subjective signs caused by this application of ointments, such as tingling, burning, and itching. In individuals with sensitive skin, these symptoms appear within 3-20 minutes after application called ointment, followed by the appearance of erythema, which begins with the periphery of the zone of application.

To date, capsaicin was used as a medicine, in particular, to relieve pain associated with shingles. Capsaicin causes release of neuropeptides from sensory nerve fibers and, in particular, the allocation of CGRP, which comes from the nerve endings of the epidermis and dermis. The applicant has found that fisiopatologia scheme common to all States sensitive skin, associated with a high ability to release neuropeptides, and more particularly CGRP in the skin. Dysesthesia symptoms that appear when you select cells, referred to as "neurogenic".

This CGRP is a polypeptide chemical element that is produced and secreted by servletunit and some dermatological diseases, for example, eczema or prurigo.

The applicant has found that one of the main characteristics of sensitive skin associated with allocating CGRP, and therefore the use of CGRP antagonists could provide for sensitive skin prophylactic and/or therapeutic effect.

Thus, for treatment of sensitive skin, the applicant proposes to use the CGRP antagonist. The applicant found that the introduction of the CGRP antagonist in a cosmetic, pharmaceutical or dermatological composition allows to avoid irritation, and/or dysesthesias sensations, and/or Zudov skin and/or mucous membranes, and/or erythema.

The object of the present invention is thus the use of at least one CGRP antagonist in the composition containing a cosmetically, pharmaceutically or dermatologically suitable environment for processing sensitive skin.

The invention makes it possible to influence the symptoms of neurogenic origin, resulting from an external agent is able to modify the biochemical and biophysical constants tissues (skin, mucous membranes).

In addition, sensitive skin is skin is expected starts with subjective symptoms (tingling, burning,...) until the inflammation.

The object of the present invention is also the use of at least one CGRP antagonist for preventing and/or combating skin irritations and/or herpes, and/or eritem, and/or burning sensations, and/or dysesthesias feelings, and/or itching of the skin and/or mucous membranes.

Cosmetically, dermatologically or pharmaceutically suitable environment is an environment that is compatible with the skin, scalp, nails and mucous membranes. The composition comprising the antagonist of CGRP may be applied to the face, neck, hair and nails, or any other area of the body covered by skin, for example, large folds (axillary areas, areas that are located under the breast, in the crease of the elbow section, and so on).

The applicant has identified antagonist GR as any molecule organic or mineral origin that are able to inhibit the fixation of the CGRP receptor or is capable of inhibiting the synthesis and/or release of CGRP sensitive nerve fibers.

The substance is considered as an antagonist of CGRP, must meet the following criteria: to have pharmacological antagonist is tov:

- the substance is an antagonist should reduce vasodilatation induced by capsaicin and/or

- the substance is an antagonist should cause inhibition of CGRP release sensitive nerve fibers and/or

- the substance is an antagonist should inhibit the contraction of smooth muscles of the excretory duct, caused by CGRP.

In addition, the antagonist may have an affinity for CGRP receptors.

No one to date has not established links between CGRP and sensitive skin. Clinical signs of sensitive skin mostly subjective: tingling, kisenyi, itching, twitching, burning, and the emergence of eritem. These symptoms occur due to external especificly factors. Symptoms appear mostly very local on the face, neck and scalp, but can also appear on the whole body.

The invention allows for the use of, for example, as antagonist GRP molecule CGRP 8-37 or molecule antibodies to CGRP.

In the compositions according to the invention, the antagonist GR is used preferably in an amount constituting from 0.000001 to 10 wt.% with respect to the total weight of the composition, in particular in amounts of 0.0001 to 5 wt.% from the new forms, usually used for local application, namely, in the form of aqueous solutions, water-alcoholic or oily solutions, dispersions of the type of lotion or serum, anhydrous or lipophilic gels, emulsions of liquid or semi-liquid consistency of the type of milk that is obtained by dispersing a fatty phase in an aqueous phase (M/W) or conversely (W/M), suspensions or emulsions of soft consistency, semi-solid or solid type of cream or gel, or alternatively of microemulsions, of microcapsules, of microparticles or of vesicular dispersions of ionic and/or anionic type. These compositions have, in accordance with conventional methods.

They can also be used for hair as water, alcohol or water-alcohol solutions or in the form of ointments, gels, emulsions, foams, or in the form of aerosol compositions also containing the agent-carrier under pressure.

The number of different components in the compositions according to the invention, likewise commonly used in the reviewed areas.

In General, these compositions are detergent creams, protective creams, creams for processing and face care, hand creams, creams for the feet, cream for the large anatomical folds or for the body (for example day creams, nocny the agrarian creams), cosmetic makeup products, for example, liquid creams, cleansing milk to remove face makeup, lotion protective and body lotion, body care, substances used after exposure to sunlight, having a form of Royal jelly, lotions, gels or foams for caring for the skin, such as lotions for cleaning or disinfection of the skin, lotions, protecting the skin from tanning, lotions, ensuring the formation of artificial tanning compositions for the bath, deodorant compositions containing a bactericidal agent, the products used after shaving (gels or lotions, creams, providing hair removal, compositions, providing protection from blood-sucking insects, the composition that relieves pain, compositions for treatment of acne, Hyperboreans skin or seborrheic dermatol or compositions for the treatment of symptoms of skin diseases like severe itching, red acne, acne, ulcers, foot, psoriasis, abscesses, scars on the skin when it is stretched.

The compositions according to the invention may also be in solid form, forming a soap or detergent bars.

The CGRP antagonist can also be introduced into various compositions for the care or treatment of the hair, namely, shampoos, possibly, anti-parasitic actions, ASCII (in particular, oxidizing dyes), possibly in the form of coloring shampoos, restoring hair lotions, compositions for perming hair (in particular, the compositions intended for the first time with a Curling iron), lotions or gels, preventing hair loss, etc.

The compositions claimed in the present invention may also find application for the care of mouth and teeth, such as tooth paste or elixir for oral. In this case, the composition may contain additives and additives normally used in compositions intended for the treatment of the oral cavity, namely, surface-active agents, thickeners, wetting agents, abrasive agents, for example, silicon dioxide, various aktivnye ingredients such as fluorides, in particular sodium fluoride, and possibly sweetening agents, for example, sharing sodium.

In the case where the composition according to the invention is an emulsion, the fatty phase may range from 5 to 80 wt.%, but preferably, from 5 to 50 wt.% with respect to the total weight of the composition. The oils, emulsifiers and simulatory used in the composition in the form of an emulsion, selected among the substances which are classically used in the cosmetic region is,5 to 20 wt.% with respect to the total weight of the composition. The emulsion may also contain lipid vesicles.

In the case where the composition according to the invention is a solution or oily gel, the fatty phase may represent more than 90 wt.% the total weight of the composition.

As usual cosmetic composition according to the invention, may also contain additives commonly used in the field of cosmetics, pharmaceutical or dermatological fields, namely, hydrophilic or lipophilic agents, gelation, active hydrophilic or lipophilic substances, preservatives, antioxidants, solvents, fragrances, fillers, filters, antibacterial substances, substances, odor absorbent, a coloring matter. The amounts of these various additives matches usually used in these areas the number, for example, from 0.01 to 10 wt.% the total weight of the composition. These additives, in accordance with their nature, can be introduced into the fatty phase, into the aqueous phase and/or into the lipid balls.

As the oils used in the present invention, can be called mineral oil (liquid paraffin), vegetable oils (liquid fraction of the oil tallow tree, sunflower oil), animal oils (pergadia oil (parfocality). May also be used as fatty substances, fatty alcohols, fatty acid series (stearic acid), waxes (paraffin, Carnauba, beeswax).

As emulsifiers used according to the invention, include, for example, glycerol stearate, Polysorbate 60 and the mixture of PEG-6/PEG-32/Glycol Stearate sold under the trademark TefoseR63 firm Dattefosse.

As solvents used according to the invention, can be called lower alcohols, namely, ethanol and isopropanol, propylene glycol.

As hydrophilic agents, gelation can be called carboxyvinyl polymers (carbomer), acrylic copolymers, such as copolymers of acrylate/alkylacrylate, polyacrylamides, polysaccharides, for example, hydroxypropylcellulose, natural rubber and clay, and as lipophilic agents, gelation can be called, modified clays, such as bentonites, metal salts of fatty acids such as aluminum stearate and hydrophobic silicon dioxide or ethylcellulose, polyethylene.

As hydrophilic active substances it is possible to use proteins or protein hydrolysates, amino acids, polyols, urea, allantoin the acts of Aloe Vera.

As lipophilic active substances it is possible to use retinol (vitamin a) and its derivatives, tocopherol (vitamin E) and its derivatives, volatile fatty acids, volatile oil.

In addition to the above, it is possible to combine the CGRP antagonists with active agents intended in particular for the prevention and/or treatment of skin lesions. Among these active agents can be called for example:

agents, modulating the differentiation and/or proliferation and/or pigmentation of the skin, namely, retinology acid and its isomers, retinol and its esters, vitamin D and its derivatives, oestrogens such as oestradiol, kojic acid or hydroquinone;

such antibacterial agents, as clindamycine, erythromycin or antibiotics of the class tetracycline;

- antiparasitic agents, in particular metronidazole, crotamiton or pyrethrinoid;

- antifungal agents, in particular compounds belonging to the class of imidazoles, such as econazole, ketoconazole or miconazole or their salts, polyene compounds such as amphotericin b, compounds of a number of allylamines, such as terbinafine or octopirox;

- steroid anti-inflammatory agents, such agents, such as ibuprofen and its salts, diclofenac and its salts, acetylsalicylic acid, acetaminophen or glycyrrhetinic acid;

- anesthetic agents, such as hydrochloride lidocaine and its derivatives;

- antipruritic agents, for example, analgin, trimeprazine or cyproheptadine at;

- antiviral agents such as acyclovir;

- keratolytic agents such as alpha - and beta-hydroxycarboxylic acids or beta-ketocarboxylic acids, their salts, amides or esters and more particularly, a hydroxy acid such as glycolic acid, lactic acid, salicylic acid, citric acid and acid fruits and h octanoyl-5-salicylic acid;

agents that reduce the formation of free radicals, such as alpha-tocopherol or its esters, the peroxide dismutase, certain metal chelating agents or ascorbic acid and its esters;

- protivoseborainey substances, for example, progesterone;

- substances that prevent the formation of dandruff, for example, octopirox and zinc pyrithione;

- substances that prevent the formation of blackheads, for example, retinoic acid or benzoyl peroxide.

The advantage of CGRP antagonists in that they can soy is used in the cosmetic, pharmaceutical or dermatological field. The presence of the antagonist GR in cosmetic, pharmaceutical or dermatological composition, containing one active substance, can significantly weaken or even eliminate this irritant effect.

In particular, antagonists GR allow to increase the number cosmetically, pharmaceutically or dermatologically active substance relative to the commonly used quantity to improve efficiency.

In addition, the object of protection of the present invention is a composition comprising a cosmetically, pharmaceutically or dermatologically suitable environment and at least one substance having an irritant side effect, characterized in that it contains at least one antagonist GR.

Irritants to which the present invention is applicable, are mainly aromatic substances, surfactants (ionic or anionic type), preservatives, some solar filters, organic solvents, alcohol solvents, and some cosmetically, pharmaceutically or dermatologically active substances.

In chattnooga, malic, citric, tartaric, almond-hydroxy acid (salicylic acid and its derivatives), a keto acid, a keto acid, retinoids (retinol and its esters, retinal, retinoic acid and its derivatives, retinoids, and more particularly those described in the materials F-a-2 570 377, EP-A-199636, EP-A-325540, EP-A-402072), anthralin (dioxiranes), anthranoid, peroxides, Minoxidil, lithium salts, antimetabolites, vitamin D and its derivatives, paints and dyes for the hair (paraphenylenediamine and its derivatives, aminophenols), fragrant alcohol solutions (perfume, toilet water, the composition used after shaving, deodorants were examined), agents that suppress the secretion of sweat (some aluminium salts), active ingredients, providing hair removal or permanent hair (thiols), substances for removing pigmentations (hydroquinone), active substances, destroying lice (pyrethrin).

The use of CGRP antagonist can significantly increase 2-10 times the number of substances, in particular active substances with irritating side effect, compared to the prior art, to the exclusion of all the above mentioned negative aspects. Thus, it is possible to use hydroxy acid in a quantity of up to 50 wt.% of the total weight of the present invention is, furthermore, the method of cosmetic treatment, characterized in that applied on the skin, the scalp and/or mucous membrane composition described above containing at least one antagonist GR in a cosmetically suitable medium.

Method of cosmetic treatment according to the invention can be implemented primarily when applying hygienic or cosmetic compositions, similar to those described above, in accordance with the conventional method of using these compositions. For example: applying ointments, gels, serums, lotions, milk to remove make-up or compositions intended for use after sun exposure, skin or dry hair, application of lotion for hair on wet hair, application of the shampoo or application of toothpaste to the gums.

The following examples illustrate the invention. In these examples, these proportions are given in weight percent.

Example 1: face Lotion to remove makeup

CGRP 8-37 - 0,50

Protivookislitelnoj - 0,05

Isopropanol - 40,00

Preservative - 0,30

Water Up to 100.00%

Example 2: face Lotion to remove makeup

CGRP 8-37 - 0,0001

Protivookislitelnoj - 0,05

Hydroxypropylcellulose (Klucel H, manufactured by Hercules) - 1,00

Protivookislitelnoj - 0,05

Isopropanol - 40,00

Preservative - 0,30

Water Up to 100%

Example 4: Gel for treatment of acne

Antibody Anti-CGRP - 0,10

All-TRANS-retinoic acid - 0,05

Hydroxypropylcellulose (Klucel H, manufactured by Hercules) - 1,00

Protivookislitelnoj - 0,05

Isopropanol - 40,00

Preservative - 0,30

Water Up to 100%

Example 5: Cream facial emulsion oil-in-water)

CGRP 8-37 - 0.02

Glitzenstein - 2,00

Polysorbate 60 (Tween 60, manufactured by S) - 1,00

Stearic acid - 1,40

Triethanolamine - 0,70

Carbomer - 0,40

The liquid fraction oil tallow tree - 12,00

Perhydrosqualene - 12,00

Protivookislitelnoj - 0,05

Odorant - 0,5

Preservative - 0,30

Water Up to 100%

Example 6: Shampoo

Lauric ether sodium sulfate (2,2 TH) - 12,00

Antibody Anti-CGRP - 0.02

Hydroxypropylcellulose (Klucel H, manufactured by Hercules) - 1,00

Odorant - 0,50

Preservative - 0,30

Water Up to 100%

Example 7: Cream facial acting anti-wrinkle emulsion oil-in-water)

CGRP 8-37 - 0,15

Glitzenstein - 2,00

Polysorbate 60 (Tween 60, vypuskaemyi,70

Carbomer - 0,40

The liquid fraction oil tallow tree - 12,00

Perhydrosqualene - 12,00

Protivookislitelnoj - 0,05

Odorant - 0,5

Preservative - 0,30

Water Up to 100%

Example 8: Emulsion gel for care, effective against insect bites (emulsion oil-in-water)

Cyclomethicone - 3,00

Oil Porcellino (manufactured by Dragocco) - 7,00

PEG-6/PEG-32/Clycol Stearate (TefoseR63 company Dattefose) - 0,30

Antibody Anti-CGRP - 0.02

Preservative - 0,30

Odorant - 0,40

Carbomer - 0,60

Crotamiton - 5,00

Glycyrrhetic acid is 2.00

Ethyl alcohol - 5,00

Triethanolamine - 0,20

Water Up to 100%

Example 9: the Gel is effective against pain

CGRP 8-37 - 0,03

Hydroxypropylcellulose (Klucel H, manufactured by Hercules) - 1,00

Protivookislitelnoj - 0,05

Hydrochloride lidocaine - 2,00

Isopropanol - 40,00

Preservative - 0,30

Water Up to 100%

Example 10: the Cream Facials, acting against red acne (emulsion oil-in-water)

CGRP 8-37 - 0,25

Glycidylester - 2,00

Polysorbate 60 (wn 60, manufactured by S) - 1,00

Stearic acid - 1,40

Metronidazole - 1,00

Triethanolamine - 0,70

Carbomer - 0,40

The liquid fraction of the oil of the sebaceous derived - Up to 100%

Example 11: care Cream effective against solar erythema (emulsion oil-in-water)

Antibody Anti-GR - 0,25

Literallayout - 2,00

Polysorbate 60 (wn 60, manufactured by ICI) - 1,00

Stearic acid - 1,40

Glycerrhetinic acid - 2,00

Triethanolamine - 0,70

Carbomer - 0,40

The liquid fraction oil tallow tree - 12,00

Sunflower oil - 10,00

Protivookislitelnoj - 0,05

Odorant - 0,50

Preservative - 0,30

Water Up To 100%.

1. The use of at least one CGRP antagonist as an agent that inhibits the release of peptide CGRP, in a composition containing a cosmetically, dermatologically or pharmaceutically suitable environment for processing sensitive skin.

2. Application under item 1 in which the CGRP antagonist is a molecule selected from the CGRP 8-37, and antibody to CGRP.

3. Application under item 1 in the topical compositions destination for preventing and/or combating skin irritations and/or herpes, and/or eitam, and/or dysesthesia, or itching of the skin and/or mucous membranes.

4. Method of cosmetic treatment, comprising applying to the skin of the scalp and/or mucous membranes HDMI is 4, characterized in that the CGRP antagonist selected from CGRP 8-37 and antibodies to CGRP.

6. The method according to p. 4 or 5, characterized in that the CGRP antagonist used in the quantity constituting 0,000001 - 10 weight. % relative to the total weight of the composition.

7. The method according to any of paragraphs. 4-6, wherein the CGRP antagonist is used in a quantity amounting to within 0.00001 - 5 wt. % relative to the total weight of the composition.

8. A composition comprising a cosmetically, pharmaceutically or dermatologically suitable environment and at least one substance with annoying side effect, characterized in that it further comprises at least one CGRP antagonist.

9. The composition according to p. 8, wherein the CGRP antagonist is selected from organic or mineral molecules.

10. The composition according to p. 8 or 9, characterized in that it contains CGRP in the quantity constituting 0,000001 - 10 weight. % relative to the total weight of the composition.

11. Composition according to any one of paragraphs. 8 and 9, characterized in that it contains CGRP in the quantity constituting of 0.0001 - 5 weight. % relative to the total weight of the composition.

12. Composition according to any one of paragraphs. 8-10, characterized in that the substance side with the irritant of vibrant, peroxides, Minoxidil, lithium salts, antimetabolites, vitamin D and its derivatives, depigmentation, solvents, fragrances, preservatives, surfactants, alcohol solutions.

13. Composition according to any one of paragraphs. 8-11, characterized in that it further comprises at least one agent selected from antibacterial agents, antiparasitic agents, antifungal agents, anti-inflammatory agents, antipruritic agents, anesthetic agents, antiviral agents, keratolytic agents, agents that prevent the formation of free radicals, protivoseborainey agents, agents that prevent the formation of dandruff, agents protivougrevoe actions and/or agents that cause differentiation and/or proliferation and/or pigmentation of the skin.

14. Composition according to any one of paragraphs. 8-11, characterized in that the cosmetically, pharmaceutically or dermatologically suitable environment is an aqueous solution, oily solution or water-alcohol solution, emulsion, water-in-oil emulsion, oil-in-water microemulsion, an aqueous gel, an anhydrous gel, a serum, a dispersion of vesicles, microcapsules or microparticles.

15. The composition according to p. 13, distinguishing splitline substance nonsteroidal type.

16. The composition according to PP. 8-12, characterized in that it is a composition for cleaning, the composition for protection, a composition for treatment, a composition for formation of a fake tan or a composition for care of the face, hands, feet, folds of the body or body product for makeup, cleansing milk to remove make-up product for the treatment of the skin after exposure to sunlight, the composition for bath, deodorizing composition, a composition for treatment of wrinkles, acne or Hyperboreans skin or seborrheic dermatol, a product used after shaving, cream hair removal, composition, protected from insect bites, composition, possessing analgesic effect, a composition for care or hair treatment, shampoos, styling hair, means for Curling the hair, products for hair coloring tools for modeling hairstyles, composition, anti hair loss, solutions for the treatment of oral cavity and teeth.

 

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