CZ19008U1 - General-purpose composition intended for prevention and treatment of acne and other skin diseases - Google Patents

Description

Technical field

The technical solution belongs to the field of pharmaceutical and munobio logical products, eventually to the area of food for special nutrition and food supplements and it concerns the composition of universal preparation serving to increase immunity, prevention, prophylaxis and treatment of acne and other skin diseases in human and veterinary medicine.

Background Art

Acne (acne vulgaris) is a multifactorial disease, because more factors contribute to its development. It is a hormone-related skin disease in which the skin microflora bacteria are also involved in their etiopathogenesis. Nowadays, the unambiguous scientific opinion prevails that excessive sebum production, horn retention in the follicle and colonization by the anaerobic microbe Propionibacterium acnes with the subsequent formation of inflammatory mediators in the follicle and the surrounding tissue, as described, for example, in Cunliffe, play a primary role in acne. IV. J .; Gollnick, H .:

Acne.Diagnosis and Management (London: Martin Dunitz Ltd, 2001, 166s) or Plewig, G .;

Kligman, A.M .: Acne and Rosacea. Springer (Verlag Berlin Heidelberg New York 2000. 744s.). Seborea and hyperkeratinization are mainly stimulated by hormonal changes, which are due both to increasing levels of androgens at puberty, but also to increased sensitivity of sebaceous glands androgens, even at their normal levels.

The bacterial flora of the follicles, especially the indirect action of the anaerobic microbe Propionibacterium: o acnes, plays an important role in the development of inflammatory processes, as described in Dené, B. -8). The mechanism of action of this microbe lies in the production of biologically active substances contributing to inflammation. The follicular epithelium of the lymphocyte and subsequent rupture of the follicle wall gradually infiltrate. The penetration of sebum, keratin, microorganisms into the dermis leads to a violent reaction of the surrounding tissue and chemotaxis of lymphocytes, neutriles and giant multinucleated cells. The result is the formation of papules, pustules, nodules and cysts. Based on the development of non-inflammatory and inflammatory manifestations, a clinical picture of lighter, moderate and severe acne forms. Immunological processes play a major role in the development and persistence of inflammatory manifestations. The extent of the inflammatory response and the clinical severity of the disease correlate with the degree of immunity to Propionibacterium ac30 nes. which is dedicated to Rulcová, J .; Vaněčková, J. et al .: Treatment of acne vulgaris (Case report in patients treated with Roaccutan, Prague 2001, I77s).

Propionibacteria affect the cellular and humoral components of the immune system when interleukin, chemotactic factors, and complement activation increase. Other skin rhinotrophic bacteria, especially Staphylococcus epidermidis and Staphylococcus aureus, have also been implicated in the etiopathogenesis of acne and other skin diseases, as discussed by Bednar. M. and Fraňková. V .. Schindler. J., Vávra, J .: Medical Microbiology (Prague. 1996, p. 292-293). The choice of acne therapy is based on the severity of the acne clinical picture and skin type. Depending on the clinical picture and the form of acne, retinoid therapy, antibiotics, benzoyl peroxide and azelaic acid are primarily chosen. for example, Rulcová J .: Acne vulgaris - from ctiopathogenesis to therapy (Pediatr pro Praxi, 2007. 1: 17-18).

Vaccine therapy is indicated for inflammatory symptoms of acne with mild and moderate severity and is economically less demanding than currently used methods of acne treatment. Presently, it is preferred to administer tablets or capsules which contain the bacterial solids obtained by a special process. No adverse effects are observed during vaccination and, unlike the currently used methods of acne treatment, after vaccination, the beneficial effects of vaccination persist over the long term, for several months or years, as described in the articles Viktorinová, M., Koukalova, D .: Our Experience in Action by acne treatment L Injectable vaccines - long-term follow-up (Czechoslovak Dermatology, 65, 1990a), No. 5. 158-165), Viktorinová. M. _t Koukalová, D .: Our Experience with Acne Vaccination Treatment 11. Oral Drop Vaccine (Czechoslovakia der5o matoloaie, 65th and 990b). No. 5, 322-327), Viktorinova, M., Koukalova. D .: Skin Testv in Microbial - 1 CZ 19008 Acne Acne Antigens (Czechoslovak Chemism 67, 1992, 140-149), Loveckova, F, Koukalova, D., Viktorinova, NL, Sauer, P., Sila, J .: Comparative study of acne treatment results with vaccines and systemic antibiotics 2. Characteristics of bacterial strains isolated from acne deposits and their resistance to antibiotics. (Ces.-Words. Derm. 82, 2007, No, 2, p.82-86; Vo), Viktorin, M.,

Koukalová, D., Kartová, L, Lovečková, Bystroň, J., Hejnar, P .: Comparative Study of Acne Treatment Results with Vaccines and Systemic Antibiotics 1. Evaluation of Therapeutic Effect (Ces.-slov. Derm. 80, 2005, No 4, p.224-228), Viktorinová, Ní., Koukalová, D .: Our Experience with Acne Vaccination Treatment 111. Oral Tablet Vaccines (Cs. Derm. 69, 1994, No.4, p. 175-178) or Koukalová, D., Viktorinová, NL: Oral Vaccine Therapy in Dermatology (Epidemiol. Nioikio biol. Immunol., 44, 1995, No. 1, p.36-43). A poly-microbial vaccine for the treatment of acne vulgaris is described in the patent specification CZ 277 674.

Earlier vaccine vaccines used to contain more bacterial strains and one bacterial agent, resulting in the given isolates of one bacterial strain not having a synergistic effect on the immune system and favoring the development of specific and nonspecific immunity to the disease. Another major drawback was the use of formalin as an inactivating agent. Thereafter, Formalin was present in the final vaccine form and had an adverse effect on the human body at the site of action. The disadvantage of the preparations was also the failure to determine exact control output criteria, such as determination of residual moisture, determination of pH range, determination of microbiological safety, precise identification of production strains by modern molecular biological methods, determination of lyophizate appearance, determination of active substance efficacy before preparation of preparations, determination of active activity substances after final discharging prior to release for use by patients, and a complicated method of dispensing these preparations by methods not entirely corresponding to the requirements of modern applications that would induce optimal non-specific and specific immunity to the disease.

The aim of the present invention is to introduce a new universal formulation which would greatly reduce the aforementioned shortcomings of the previously used acne vaccine or dermatology vaccines and eliminate the abnormality of the formulations used resulting in adverse effects regarding the safety and efficacy of the preparations. The new universal preparation contains a bacterial lysate in a lower combination of at least one, two, preferably all three or more of the most important pathogenic bacterial strains involved in the etiopathogenesis of acne or other skin diseases. The composition can be administered by the oral route, orally, by mouth, on the skin, by injection or otherwise, to provide a solid non-specific and specific immunity to the disease. Administration of the product is in line with the latest findings on the molecular nature of the effect of bacterial immunomodulators and thus is highly effective and innocuous in the established mode of administration, consistent with the conclusions of Weigl, E., Raška, Ní., Boháč, S .: Molecular Basis of the Effect of Bacterial Immunomodulators (Allergy, No.3, 2000, 1-9). The formulation allows manufacturing and testing in such a way that each batch is homogeneous and standard to ensure the harmlessness and efficacy effect after administration.

The essence of the technical solution

The goal achieved, to a large extent, meets the requirements of a universal preparation intended for the prevention and treatment of acne and other skin diseases, based on bacterial lysates of bacterial bacterial strains causing acne and other skin diseases. in combination with strains of Staphylococcus aureus and / or Staphylococcus epidermidis and / or Propionibacterium acnes.

It is a further object of the invention that the composition comprises strains of Staphylococcus aureus CCM 7587, Staphylococcus epidermidis CCM 7588, Propionibacterium acnes CCM 7586, and preferably comprises:

5 to 45% by weight of Staphylococcus aureus strain CCM 7587

5 to 45% by weight of Staphylococcus epidermidis strain CCM 7588

10 to 90% by weight of Propionibacterium acnes CCM 7586 strain.

CZ 19008 Ul

It is also within the scope of the present invention that the total bacterial dry matter content of all production strains at a single application rate is in the range of 1 to 1000 mg and that the active ingredient mixture is mixed with up to 100 times the amount of physiologically acceptable vehicle.

It is also essential that the physiologically acceptable vehicle is selected from the group consisting of silica and / or lactose and / or potato starch and / or magnesium silicate and / or magnesium stearate and / or propyl galan and / or sodium glutamate and / or indigo carmine and / or gelatin and / or Xylitol and / or Mannitol and / or Erythritol and / or hydroxypropylmethylcellulose and / or microcrystalline cellulose and / or sodium carboxymethyl cellulose and / or magnesium stearate and / or aluminum hydroxide and / or aluminum phosphate.

Finally, it is the object of the present invention that the active compound / vehicle mixture is supplemented with additives wherein the additives are preferably selected from the group of vitamins and / or minerals and / or trace elements and / or immunobiological additives and / or flavors and / or adhesins and / or or glucans-based disinfectants and / or immunomodulatory agents.

The present product exhibits a new standard effect with a broad spectrum of efficacy by not only affecting a wide range of the most frequently occurring acne agents, but also other infectious skin diseases. In addition, the formulation is applicable in various solid or liquid forms or sprays such as injections, capsules, capsules, lozenges, tablets, globules. chewing gums or syrups, teas, mouthwashes, toothpaste or oral suspensions, powders, powders, ointments, sprays, as well as other unnamed modes of application, which also broadens its use.

Examples of technical solutions

In the preparation of the preparation, the production strains are individually propagated in a suitably selected culture medium in an air or air-free atmosphere at previously experimentally verified temperatures ranging from 20 ° to 40 ° C for a suitably selected period of 20 to 75 hours. Enriched cultures are rinsed with sterile water for injection and disintegrated by multiple freezing and inactivated. After checking for microbiological safety and identity verification, all meat of individual inactivated bacterial strains is micronized and lyophilized. The enrichment of the individual bacterial production strains can be advantageously carried out in the large-scale production by static cultivation in the culture flasks, or by fermentation in the fermenter.

Thereafter, the individual lyophilized bacterial lysates of the individual production bacterial strains are mixed with a suitable vehicle such that the proportion of individual bacterial lysates in the finished product corresponds to the selected unit weight ratios and the total composition content is 1 to 1000 mg of active substance per application dose. Finally, the final product is formulated into selected user forms, i.e., capsules, tablets, and the like, or the liquid phase product is filled into vials.

These examples do not limit the utility of this utility model.

Example 1

Composition of one tablet for oral administration:

- Staphyloeoccus aureus production strain (CCM 7587)

- Staphyloeoccus epidermidis production strain (CCM 7588)

- production strain Propionibacterium acnes (CCM 7586)

Xylitol T base vehicle, Mannitol, Hypromellose, Croscarmellose Sodium, Magnesium stearate, Erythritol, glucal. Aroma menthol mg bacterial lysates 2 mg bacterial lysates 2 mg bacterial lysates

494 mg.

CZ 19008 Ul

Example 2

Single dose composition for injection:

- Staphyioeoccus aureus production strain (CCM 7587)

- Staphyioeoccus epidermidis production strain (CCM 7588)

- production strain Propionibaeterium acnes (CCM 7586)

- aluminum oxide

- water for injectione

0.5 mg bacterial lysate 0.5 mg bacterial lysate 0.5 mg bacterial lysate 2 mg AI ⁱⁿ ad 1 ml.

Example 3

Composition of one capsule for oral application:

the production strain of Staphyioeoccus aureus (CCM 7587) 1.66 mg of bacterial lysate

- Staphyioeoccus epidermidis production strain (CCM 7588) 1.66 mg bacterial lysate

- production strain Propionibaeterium acnes (CCM 7586) 1.66 mg bacterial lysate

silica vehicle, lactose, potato starch 200 mg.

(5 Industrial Usability

A special universal preparation of the mentioned composition is useful for increasing immunity, immunotherapeutics, immunopreventive and immunoprofylactics, especially against acne and other skin diseases. It can be applied simultaneously with the use of pharmaceuticals, antibiotics or other prophylactic and therapeutic agents and vaccines. for children, men and women of all age categories, in various dosage forms for injection, oral and topical administration.

Claims (8)

PROTECTION REQUIREMENTS A universal preparation for the prevention and treatment of acne and other skin diseases, based on bacterial lysates of production bacterial strains causing acne and other skin diseases, characterized in that they are individually selected as active ingredients. 25 or in combination with each other strains of Staphyioeoccus aureus and / or Staphyioeoccus epidermidis and / or Propionibaeterium acnes. The universal preparation according to claim 1, characterized in that it comprises strains of Staphyioeoccus aureus CCM 7587, Staphyioeoccus epidermidis CCM 7588, Propionibaeterium acnes CCM 7586. ;and. Universal preparation according to claims 1 and 2, characterized in that it comprises a mixture of: 5 to 45% by weight of the strain Staphyioeoccus aureus CCM 7587 5 to 45% by weight of the strain Staphyioeoccus epidermidis CCM 7588 10 to 90% by weight of the Propionibaeterium acnes strain CCM 7586. 15 Dec The universal preparation according to claims 1 to 3, characterized in that the total bacterial dry matter content of all production strains in a single application rate ranges from 1 to 1000 mg, CZ 19008 Ul Universal formulation according to claims 1 to 4, characterized in that the active ingredient mixture is mixed with up to 100 times the amount of physiologically acceptable vehicle. Universal formulation according to claim 5, characterized in that the physiologically harmless vehicle is selected from the group consisting of silicon dioxide and / or lactose and / or potato starch and / or magnesium silicate and / or magnesium stearate and ^z or propyl and / or glutamate sodium and / or indigo carmine and / or gelatin and / or Xylitol and / or Mannitol and / or Erythritol and / or hydroxypropylmethylcellulose and / or micro crystalline cellulose and / or sodium carboxymethyl cellulose or magnesium stearate or aluminum hydroxide or aluminum phosphate. A special preparation according to any one of claims 1 to 6, characterized in that. The mixture of active ingredients and the vehicle is supplemented with additives. The special preparation according to claim 7, characterized in that the additives are selected from the group of vitamins and / or minerals and / or trace elements and / or immunobiological additives and / or flavors and / or adhesins or disinfectants and / or glucan-based immunomodulators.