RU2517239C1 - Cream for external treatment of graham-little-piccardi-lasseur syndrome - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention discloses a cream for external treatment of Graham-Little-Piccardi-Lasseur syndrome, which contains lanolin, peach oil and distilled water, and is characterised by that it further contains chloroquine, wherein components of the cream are in a defined ratio given in g%.

EFFECT: inhibiting progression of scarring without marked side effects.

Description

The invention relates to medicine, in particular to the field of dermatovenereology and cosmetology, and can be used for external therapy of Piccardi-Graham-Little-Lassiuer syndrome. The essence of the invention lies in the fact that the claimed non-steroidal external drug in the form of a cream contains chloroquine, lanolin, peach oil, distilled water in the following ratio of components:

Chloroquine 1-1.5 g%

Lanolin 33-35 g%

Peach oil 33-35 g%

Distilled water 20-28.5 g%.

Known cream (for the therapeutic and prophylactic treatment of skin diseases) “Dermoveit”, containing: clobetasol propionate, propylene glycol, sorbitan sesquioleate, white soft paraffin, distilled water (Bozhchenko A.A. Cicatricial and non-cicatricial alopecia: classification, etiology, pathogenesis, clinical paintings and therapies // Journal of Dermatovenerology and Cosmetology. - 1998. - No. 2. - P. 45-54; Mashkovsky MD. Medicines. In 2 volumes, 14th ed. - M .: LLC "New Wave", Publisher S.B. Divov, 2002. - v. 1. - 544 s .; t. 2. -608 s.).

Known cream (for the correction of skin diseases) "Cold cream", which contains: lanolin 30 g%, peach oil 30 g%, distilled water 30 g% and which is used in the treatment of skin diseases (Dermatovenerology: a textbook for medical schools / A. V. Samtsov, V.V. Barbinov. - St. Petersburg .: SpetsLit, 2008, - 352 p.).

The disadvantage of Dermoveit is its high cost, as well as the presence of significant side effects when used externally, such as skin atrophy, scarring, steroid dependence, and the effect of withdrawal. The use of this cream in the case of Piccardi-Graham-Little-Lassiuer syndrome does not meet the needs for the treatment of this dermatosis, as it can lead to further scarring due to side effects.

The disadvantage of Cold Cream is that it does not contain the necessary active ingredients for the prevention and treatment of scarring in the Piccardi-Graham-Little-Lassiuer syndrome.

The purpose of the invention is to develop an economically acceptable non-steroid cream composition with therapeutic and prophylactic properties for external correction of the Piccardi-Graham-Little-Lassiuer syndrome and rapidly inhibiting the progression of scarring, with no pronounced side effects.

The goal is achieved by the fact that people with Piccardi-Graham-Little-Lassiuer syndrome are prescribed a cream containing chloroquine 1-1.5 g%, lanolin 33-35 g%, peach oil 33-35 g%, distilled water 20 -28.5 g%.

The cream is prescribed externally twice a day to the lesions, in a thin layer, for two months of therapy.

The cream is used as follows. For patients with Piccardi-Graham-Little-Lassieuer syndrome, a cream containing chloroquine 1-1.5 g%, lanolin 33-35 g%, peach oil 33-35 g%, distilled water 20-28, is prescribed as external therapy 5 g%. The cream is prescribed externally in the form of lubrications twice a day to the lesions, for two months of therapy.

Chloroquine is a crystalline powder, bitter in taste, white or white with a light creamy tint. Easily soluble in water, very little in alcohol.

It is well and quickly absorbed in the gastrointestinal tract, the maximum concentration (Cmax) is 2-6 hours; partially undergoes biotransformation and is slowly excreted from the body (elimination half-life (T1 / 2) is 30-60 days). Used in the treatment of skin diseases. The spectrum of action of chloroquine is aimed at inhibiting the synthesis of nucleic acids, reduces the activity of certain enzymes, and slows down immunological processes.

Chloroquine is widely used in the treatment of collagenoses: systemic lupus erythematosus, scleroderma, and especially rheumatoid arthritis (in the latter case, it is considered as one of the basic drugs).

It is believed that the therapeutic effect of chloroquine is based on an immunosuppressive effect, a predominant effect on the metabolism of immunocompetent cells, as well as connective tissue (Mashkovsky M. D. Medicines. In 2 volumes, 14th ed. - M .: New Wave ", Publisher S.B. Divov, 2002. - Vol. 1. - 544 p .; Vol. 2. - 608 p.).

The results of our scientific research indicate the effectiveness of chloroquine in immunological skin diseases, leading to scarring, in particular. Piccardi-Graham-Little-Lassiuer syndrome. Chloroquine is added to the cream composition and used to treat these diseases.

To prove the achievement of the purpose of the invention, we conducted clinical trials on the basis of the clinic of skin and venereal diseases of the Military Medical Academy to evaluate the impact of the effectiveness of the proposed cream for the treatment of Piccardi-Graham-Little-Lassiuer syndrome (Bozhchenko A.A. Scar and non-scar alopecia: features pathogenesis and therapy: Dis .... Candidate of medical sciences - St. Petersburg, VMAA, 1999. - 255 years; Samtsov A.V., Bozhchenko A.A. Dermatohistopathological changes in the Piccardi-Graham-Little-Lassuer syndrome. // Actual question dermatology, mycology and sexually transmitted infections. - Blagoveshchensk: AGMA, 2000. - P. 120-121; Samtsov A.V., Bozhchenko A.A. Piccardi-Graham-Little-Lassuera syndrome: histopathological studies. // Patriotic Dermatovenerology-2000: Problems, Searches, Solutions: Collected Scientific Products - Nizhny Novgorod: Publishing House of the Volga-Vyatka Academy of Public Administration, 2000. - P. 11-12; Samtsov A.V., Barbinov V.V. ., Sukharev A.V., Bozhchenko A.A. Piccardi-Graham-Little-Lassuer syndrome: dermatohistopathological and local immunological changes. // Actual questions of dermatovenerology: Anniversary. Sat scientific tr. II.- Kursk, 1999 .-- S. 82-83; Samtsov A.V., Bozhchenko A.A. Piccardi-Graham-Little-Lassuer syndrome: an integrated clinical, dermatohistopathological, immunological and endocrinological study. // Vestn. Dermatol. and venereol. - 2001. - No. 6. - S. 4-11; Bozhchenko A.A., Matrunetskiy O.N., Alpatov V.N. Changes in some biochemical parameters of the peripheral blood of patients with Piccardi-Graham-Little-Lassuer syndrome. // Young scientists and specialists - health care in St. Petersburg in the XXI century. - St. Petersburg, VMAA, 2000 .-- S. 15-16; Sukharev A.V., Bozhchenko A.A., Alpatov V.N., Matrunetskiy O.N. Some features of the violation of the endocrine status of patients with Lassuer-Little syndrome. // V All-Russian scientific-practical conference. "Actual issues of diagnosis and treatment in a multidisciplinary medical institution," April 26-27, 2001. - St. Petersburg: BI, 2001. - P. 140).

The object of the study was people with Piccardi-Graham-Little-Lassiuer syndrome.

Four groups of subjects were formed: three observation groups and a control group. Groups were formed from individuals suffering from Piccardi-Graham-Little-Lassuer syndrome and voluntarily agreed to participate in the study. The size of each group was 20 people, which was sufficient to obtain representative conclusions from the research results.

External treatment of the first group was carried out with Dermoveit cream, external treatment of the second first group was carried out with Cold Cream, external treatment of the third group was carried out with a cream containing chloroquine, lanolin, peach oil, distilled water with the following ratio of components: chloroquine 1-1.5 g%, lanolin 33-35 g%, peach oil 33-35 g%, distilled water 20-28.5 g%, control group individuals received placebo as an external treatment.

The study of the effectiveness of the use of creams was carried out on the basis of clinical studies, biochemical, endocrinological studies, histological and immunohistochemical studies of skin biopsies (Bozhchenko A.A. Some features of the general and external treatment of patients with chronic inflammatory dermatoses with irreversible damage to the sebaceous apparatus. // Young scientists and specialists - health care in St. Petersburg in the XXI century. - SPb., VMAA, 2000. - S. 16-17 .; Bozhchenko AA Experience in general and external therapy of patients x inflammatory rheumatoid dermatoses with irreversible damage to the sebaceous hair apparatus. // V All-Russian scientific-practical conference "Actual issues of diagnosis and treatment in a multidisciplinary medical institution", April 26-27, 2001. - St. Petersburg: BI, 2001. - P. 33; Bozhchenko A.A. Chronic inflammatory dermatoses with irreversible damage to the sebum-hair apparatus: the experience of complex dermatological therapy. // Bulletin of the Russian Military Medical Academy. - 2009. - No. 1 (25), Ave., Ch P. - S. 638; Bozhchenko A.A. Chronic inflammatory dermatoses with irreversible damage to the sebaceous system: our experience of modern complex dermatological therapy. // III Russian scientific-practical conference. "St. Petersburg Dermatological Readings", September 17-18, 2009: Abstracts. conf., St. Petersburg: "Man and his health." - S.10-11; Bozhchenko A.A. The experience of modern complex dermatological therapy of chronic inflammatory dermatoses with irreversible damage to the sebaceous hair. // IV Russian scientific and practical. conf. "St. Petersburg Dermatological Readings", October 21-22, 2010: Abstracts. conf., St. Petersburg: "Man and his health." - S. 25-26.).

In addition to examination, collection of medical history and life history data, general clinical, serological, immunological, biochemical, endocrinological blood tests, coagulograms, light microscopy of the removed hair and examination of the scalp in the rays of the Wood lamp, all patients underwent diagnostic skin biopsy of the scalp with subsequent histological examination, as well as immunophenotyping of cell subpopulations in cryostat sections. If there are relevant complaints and deviations in the blood and urine tests, additional studies were performed on the patient to identify foci of chronic infection and endocrine pathology, including orthopantomography, radiography of the paranasal sinuses, radiography of the Turkish saddle, ultrasound examination of the thyroid gland, abdominal organs and pelvis, consultation maxillofacial surgeon and ENT specialist doctor, as well as consultations of a gynecologist, endocrinologist, neuropathologist and psychiatrist (with written securing consent of the patient).

Diagnostic excision [Raznatovsky IM et al., 1995] deep [Cockerell C.J., 1994; Pinkus N. et al., 1981] a biopsy of the scalp was performed according to the method of Goldstein L.M. et al. (1987). The biopsy specimen was collected at the border of the freshest [Cockerell C.J., 1994] foci of baldness. Histological examination was carried out using the hematoxylin and eosin staining method, the eosin-Gram method according to the Weigert method, the Malloc ary azarmine method in the Heidengain modification, the Masson method, the Hale method, and the SIR reaction [Lewer W.F., 1958; Pearse A. G. E., 1962]. In the process of histological examination according to the method of Raznatovsky I.M. et al. (1995) using an EC-BIMAM R-13 light microscope (LOMO, Russia) studied at least two scalp skin preparations obtained from one patient, and at least five vertical sections were studied in each preparation [Baden N. R., 1987].

Subpopulations of T- and B-lymphocytes in cryostatic sections of biopsy specimens were determined using the indirect immunofluorescence method using monoclonal antibodies (MKAT) to receptors CDla, CD3, CD4, CD8, CD 14, CD16, CD20 (DAKO, Denmark), and immunoglobulin deposits A, M and G - by direct immunofluorescence method using monospecific antisera to these immunoglobulins (Sevac, Czech Republic). In a microscopic study of the preparations obtained, we counted labeled cells or immunoglobulin deposits in a LUMAM-IZ luminescent microscope (LOMO, Russia) with an increase in X280 and water immersion. For each MKAT name or monospecific antiserum, at least 3 sections of 9 visual fields in each were examined, while paying attention to the location of labeled cells (in the epidermis, in the dermis, in the follicular epithelium); the results were processed by a semi-quantitative method: the absence of cells labeled with MKAT corresponded to 0 points, from 1 to 5 cells in the field of view - 1 point, from 6 to 15 cells in the field of view - 2 points, from 16 to 25 cells in the field of view - 3 points , from 26 cells - 4 points.

To assess the effectiveness of treatment, in addition to special methods of clinical examination, we used the following semi-quantitative methods:

1) a test of Zalkind E.S. (1959);

2) counting the amount of hair [Gray J. et al., 1999] remaining on the pillow after a night’s sleep, on the comb - after the first day comb, on the net - after taking a shower with a head wash;

3) noted the time onset of hair growth;

4) counting the number of hair growing in the lesions on the area of 9 cm and their characteristics (fluffy, gray long, pigmented long).

The treatment effect was evaluated on a scale:

1) improvement (1 point) - test Zalkind E.S. is negative; the results of hair tension tests and counting the amount of hair significantly differ from those before the start of therapy; in patients with Piccardi-Graham-Little-Lassier syndrome, it was possible to achieve a cessation of the scarring process;

2) lack of effect (0 points) - no changes in the clinical picture of the disease are observed;

3) deterioration (-1 point) - there is a negative dynamics in the clinical picture and the results of special tests (see above).

The results of the study were statistically processed, and the following types of statistical analysis were used:

1) calculation of the numerical characteristics of a random variable according to the results of observations;

2) assessment of the accuracy and reliability of the average value of a random variable;

3) determination of relative frequency values based on the results of sample observation;

4) assessment of the accuracy and reliability of the relative magnitude of the frequency;

5) verification of statistical hypotheses based on the results of sample observation by the parametric Student's t test (t) and Fisher (F), as well as non-parametric by Pearson criterion (χ ² ), Mann-Whitney inversion criterion (U), Kruskal-Wallis rank criterion (H ), the Wilcoxon rank criterion (T) and the Wald-Wolfowitz series criterion (S);

6) correlation analysis using the parametric Pearson pair correlation coefficient (r _xy ), as well as nonparametric - Kandal correlation coefficient (τ) and Spearman's rank correlation coefficient (association coefficient) (ρ);

7) multivariate analysis of variance according to the scheme of the Latin square of the second order.

Research Results:

During the follow-up examination of patients with Piccardi-Graham-Little-Lassieuer syndrome 2 months after the start of treatment, it was found that the effectiveness of the above methods of external therapy was equal when using the proposed non-steroidal anti-inflammatory cream - 0.97 ± 0.12 [points], when using " Dermoveita ”- 0.62 ± 0.18 [points], when using Cold cream - 0.20 ± 0.37 [points], in the control group (placebo) - -0.5 + 0.5 [points].

Thus, the effectiveness of the cream we proposed was 0.97 ± 0.12 [points] or 97%, and statistically significantly differed upward when using Cold cream (S = 11; p <0.05) and Dermoveyta ( S = 15; p <0.05) in the comparison groups, and was significantly higher than when using placebo in the control group (S = 9; p <0.05).

The proposed cream formulation can reduce the activity of the immunopathological process in the skin of the scalp of patients, which helps to prevent scarring in the skin in patients with Piccardi-Graham-Lassiuer-Little syndrome.

Naturally, the proposed and studied cream containing chloroquine 1-1.5 g%, lanolin 33-35 g%, peach oil 33-35 g%, distilled water 20-28.5 g%, cannot and should not completely replace complex dermatological therapy of patients with the syndrome (regimen, diet, general therapy, external therapy, physical treatment methods). The main purpose of its application is the maximum possible correction of various disorders of the immune processes in the skin of the scalp that occur with Piccardi-Graham-Lassiuer-Little syndrome. This cream has a therapeutic and prophylactic effect on the foci of scarring, primarily due to its non-steroidal immunosuppressive effect.

Claims (1)

Cream for the external treatment of Piccardi-Graham-Little-Lassier syndrome, including lanolin, peach oil, distilled water, characterized in that it additionally contains chloroquine, in the following ratio of components:
Chloroquine 1-1.5 g%
Lanolin 33-35 g%
Peach oil 33-35 g%
Distilled water 20-28.5 g%