FR2886155A1 - Use of Tephrosia purpurea extract for the preparation of a pharmaceutical or dermatological composition to prevent and/or treat stomatodynia - Google Patents

Abstract

Use of Tephrosia purpurea extract for the preparation of a pharmaceutical or dermatological composition to prevent and/or treat stomatodynia. ACTIVITY : Analgesic. MECHANISM OF ACTION : None given.

Description

USE OF A TEPHROSIA PURPUREA EXTRACT FOR

Claims (1)

The present invention relates to the prevention and treatment of mucosal disease, more particularly of the oral mucosa. The invention relates especially to the prevention and treatment of stomatodynia. Stomatodynies are glossys of psychogenic origin without organic support. It is most often a burning sensation localized to part of the oral cavity, most often the tip of the tongue. Sometimes, the patient also complains of tingling, dysaesthesia or gene. The intensity of the burns is usually important and its chronicity resonates on the daily life of the patient. The chronology of the stomatodynies makes it possible to specify the type. Type I is present every day, absent in the morning upon waking, appearing and gradually increasing during the day to disappear in the evening, calmed by food. Type II corresponds to a Stomatodynia present all day and every day. Type III is pain that occurs only on certain days and has unusual localization. Stomatodynia most often affects women between the ages of 50 and 70 years. Examination of the oral cavity is normal. The origin of stomatodynia is either psychogenic (psychogenic oral paresthesia, carcinophobia, psychosis) or organic. The treatment of psychogenic stomatodynies is based, if necessary, on antidepressant treatment or psychological care, which is usually not very effective. Indeed, these subjects usually show signs of depression (sadness of mood, psychomotor inhibition, disinterest, insomnia, abnormal fatigability, loss of self-esteem) and signs of anxiety. The organic causes include xerostomia, intolerance and allergy to prostheses, contact allergy, glossitis (vitamin B12 deficiency, folic acid, or other vitamins of group B), disorders of dentate, lesions such as fissured tongue, geographic tongue or median rhombic glossitis. Stomatodynia is a frequent and chronic symptomatology; however, it is difficult to specify the exact frequency (about 40% of patients consulting in stomatology and dentistry whether in the hospital or in the city). The results of research obtained by the Applicant have now made it possible to highlight the interest of a mouthwash containing tephroline in the indication of stomatodynia of psychogenic origin. A good correlation was obtained with a decrease in the anxiety criterion. Tephroline is a plant-based active that stimulates the synthesis of 13-endorphin by keratinocytes. It is an extract of the seed of Tephrosia pupurea that has been proposed as a cosmetic active providing a feeling of well-being. Tephrosia purpurea is a plant in the tropics. It is widely used in India, but also on the African and South American continent. It is a plant found in the wild in a variety of ecosystems (river beds, along roads, in plain and altitude). It is in the form of a shrub 30 to 60 cm high, whose flowers are red purplish. Its seeds are 2-4 mm long and are yellow-brown in color. Their harvest is carried out in January. In India, Tephrosia purpurea is generally grown as a green manure in paddy fields or in banana and coconut plantations. It is also very popular for its many applications in traditional Ayurvedic medicine and Unani. The subject of the invention is therefore the use of an extract of Tephrosia purpurea for the preparation of a pharmaceutical or dermatological composition intended for the prevention and / or treatment of stomatodynies. Preferably, the composition of the invention is intended for the prevention and / or treatment of psychogenic stomatodynies. The extract of Tephrosia purpurea forming part of a composition according to the invention is advantageously an extract rich in amino acids, oligopeptides and oligosaccharides. Oligosaccharides represent 10% of the mass of the seed. The seed also contains mineral salts (about 15%), retinoids, monosaccharides and osides including sucrose, raffinose and two markers of activity stachyose and ciceritol. Ciceritol is a triose of α-D-galactopyranosyl- (1-6) -α-D-galactopyranosyl- (1-2) -4-methyl-chiro-inositol structure. Stachyose is a tetraose of α-D-alactosyl- (1-6) -α-D-galactosyl- (1-6) -α-D-glucosyl- (1-2) -13-D-fructose structure. In a preferred embodiment, the invention relates to a pharmaceutical composition in the form of a mouthwash.   A composition according to the invention preferably comprises about 10% by weight of the extract, water and optionally at least one acceptable excipient.   Other advantages and characteristics of the invention will become apparent from the following examples relating to the preparation of a composition based on an extract of Tephrosia purpurea and its use for the treatment of stomatodynia.   EXAMPLE 1 Preparation of a 10% Solution of Tephroline Solutions for mouthwashes according to the invention can be prepared as described in the prior art for example with the following references: http://www.vidal.fr/Medicament /hextril-8226.htm - http: //www.vidal. en / Medicament / hextril-8226.htm - http://www.vidal.fr/Medicament/alodont645.htm http://www.vidal.fr/Medicament/alodont-645.htm As additional examples may mention the following compositions: - Oxygenated water at 10 volumes% 100 CC + saline 300 CC in mouthwash or local application with compresses.   - Metronidazole (Flagyl) 4% injectable: 120 ml + 380 ml 25 distilled water + Essence of lemon or mint XV drops: soak compresses to pass on the oral mucosa.   - 50 ml of 1.4% sodium bicarbonate + 250 ml of physiological saline + 2 ml of Nystatin in suspension + 2 ampoules of polyvitamin Hydrosol.   In all cases, the patent extract is easily introduced within the available volume generally held by water or physiological saline.   As a specific example, mention may be made of the following composition: TP extract (10%), physiological serum (89%), 96% ethanol (0.9%), peppermint essence, menthol, qs 100%.   The extract TP can be obtained according to the scheme of FIG.   From the concentrated extract of the production of Tephroline 400-400200, the following tests were carried out 1) introduction in a 220 liter milk tank 2) addition of butylene glycol 1.3 (37.5% / gross commitment 3) filtration on charcoal lenses of 2 * 16 is about 7 kg of coal: filtration in looping 4) adjustment to 4% of MST by addition of butylene glycol 1,3 and osmosis water (proportion 30/70) 5) sterile filtration (0.2 micron). Example 2: Treatment of stomatodynia 1) A preliminary test was carried out on 10 patients aged between 20 and 80 years. The clinical diagnosis of stomatodynia has been confirmed by: burning sensation of the mouth gradually increasing during the day, variable but predominant topography in the tongue, improved during feeding and not impairing sleep. Medical, stomatological and surgical histories are noted as well as the notion of possible smoking intoxication. Other signs possibly associated were noted: metallic taste, salty or peppered, sensation of dry mouth, intense thirst, dysgeusia, discomfort with the speech. Examination of the oral cavity has verified the absence of any pathology of the oral mucosa, the presence or absence of an erythema of the tip of the tongue and the appearance of saliva (normal or foamy). Possible treatment with antidepressant medication or psychotherapy was also noted.   Subjects applied the solution of Example 1 (in butylene glycol - Lot No. 04133) to the oral cavity in mouthwash (for 3 to 5 minutes) 3 times daily for one month.   The improvement of the symptomatology was evaluated at OJ and D30 on the following signs: pain, tingling, burning, discomfort (analog scale from 0 to 10). An average of this criterion was performed in OJ and D30 on the 10 patients.   Using a questionnaire, the psychological state (depression and anxiety) of the patients was clarified, as well as their quality of life before and after the treatment. For this, the patient answers 23 questions asked by the doctor, following a scale of 0 to 10 depending on the intensity of the evaluated criterion. Nine questions specify the criterion Depression, seven others the criterion anxiety and finally seven questions for the quality of life.   At OJ and D30, the sum of the scores obtained for each criterion is calculated.   At D30, tolerance was assessed using semi-quantitative scores: excellent = score 3, good = score 2, mean = score 1, bad = O score. Compliance was also assessed (excellent = score 3, good = score 2, average = score 1, bad = score 0): the patient left the study if he failed to take his treatment for more than 5 days A self-assessment booklet was given to the patient so that during treatment on day 7, day 14 and day 21, he can note the evolution of the oral burning sensation and the repercussions on his psychological state and his quality of life by using a semi-quantitative score of 0 to 5 (no modification = score 0, very slight improvement = score 1, slight improvement = score 2, moderate improvement = score 3, significant improvement = score 4, very important improvement = score 5.   An average of these criteria was performed on D7, D14, D21 and D30 on the 10 patients.   A statistical analysis to allow a comparison of each criterion before and after treatment was performed using Student's paired test with a 5% alpha risk.   The evaluation of the psychological state (anxiety and depression) of the patient at OJ and J30 is reported in Tables 1 and 2 below. Table 1   Anxiety OJ J30 1 40 30 2 25 12 3 13 10 4 47 38 41 33 6 45 24 7 48 8 8 41 41 9 28 8 11 31 26 average AND, n = 10 35.9 10.7 23 12 * *: difference statistically significant compared to OJ (Student paired test, p <0.05). Table 2   Depression OJ J30 1 23 17 2 44 25 3 16 15 4 44 32 30 30 6 43 64 7 68 17 8 56 56 9 42 39 11 34 45 average AND, n = 10 40 14.4 34 16 Highlighted a statistically significant decrease of the anxiety score at day 30 compared with OJ in 9 out of 10 cases (score of 23 versus 35, 9, p <0.05). For one patient, the anxiety was not modified by the treatment.   On the other hand, Tables 3, 4 and 5 below report self-evaluation by the patient of the efficacy of the tested product on its quality of life, stomatodynia and psychological state. Table 3   Quality of life OJ J30 1 30 25 2 26 30 3 65 65 4 46 47 42 46 6 48 39 7 10 25 8 41 41 9 59 59 11 26 41 average AND, n = 10 39.3 15.7 41.8 12 Table 4 below reports the patient's self-assessment of the efficacy of the tested product on stomatodynia, psychological status and quality of life using a semi-quantitative score of 0 to 5. Table 4   Stomatodynia J7 J14 J21 J30 1 0 1 0 0 2 3 4 3 3 3 1 3 4 4 4 3 4 5 5 1 1 1 1 6 2 2 3 3 7 2 3 3 3 8 0 0 0 0 9 0 1 2 0 11 1 1 1 1 mean AND 1.3 1.1 2 1.3 * 2.2 1.6 * 2 1.7 * *: statistically significant difference compared to J7 (Student paired test, p <0.05) Table 5   Psychological state J7 J14 J21 J30 and quality of life 1 0 0 0 0 2 2 3 3 3 3 3 3 4 4 4 2 3 4 4 0 0 1 1 6 0 0 0 0 7 1 1 0 0 8 0 0 0 0 9 0 1 2 1 11 0 0 0 0 mean AND 0.8 1 1.1 1.3 * 1.4 1.6 * 1.3 1.6 * *: statistically significant difference from J7 (Student paired test , p <0.05) As of J7, we see an improvement in these criteria analyzed with a score greater than 0: 1.3 for the criterion stomatodynie and 0.8 for the second criterion. At day 14, the improvement persists and increases statistically significantly compared to J7: for criterion 1, score 2 (p <0.05) and for criterion 2: score of 1.1 (p <0.05) .   2) Ten women were included in the study. The average age was 61, 2 11.7 years (the youngest being 35 years old and the oldest being 76 years old).   The date of onset of stomatodynia is variable: for 2 patients 2 and 5 months before the start of the study and between 1 and 11 years for the other 8 patients.   Six out of ten patients take anti-depressant treatment. Adherence was good in 9 patients. One of them temporarily interrupted her treatment for 4 days following gastroenteritis. Tolerance was excellent in 9 patients. Only one patient reported a feeling of soft mouth between the 4th and the 78th day, without stopping her treatment.   The results of the clinical evaluation using an analog scale of the functional signs (burn, discomfort, pain: scale from 0 to 10) to OJ and J30 are set out in Table I below. Table 6   OJ J30 1 7 4 2 7 5 3 9 0 4 7 3 10 7 6 8 5 7 8 4 8 8 8 9 9 8 11 10 6 average AND, n = 10 8.3 1.1 5 2.3 * *: statistically significant difference compared to OJ (Student's paired test, p = 0.009) Of the ten patients tested, 8 had a decrease in the intensity of oral blight; one patient observed a complete disappearance of her stomatodynia after 1 month of treatment and one patient did not obtain a modification. The average score of intensity of oral burn is at OJ of 8.3 versus a score of 5 at D30. This difference is statistically significant (p <0.005).   This improvement corresponds to a significant decrease in stomatodynia by 40% at day 30 compared to OJ (p = 0.0009).   Bibliographic References - Killough S, Rees T, Lamey PJ. Demographic study of subtypes of burning mouth syndrome in a UK and USA population. J Dent Res 1995, 74: 892.   - Grushka M, Silverman S, Chinn H. Burning mouth syndrome. Oral Oral Surg Med Oral Pathol 1987, 63: 30-6.   Lamey PJ. Burning mouth syndrome. Dermatol Clin 1996, 14: 339-54-Grushka M, Epstein JB, Gorsky M. Department of Oral Medicine and Diagnostic Sciences, University of Illinois, Chicago, USA.   mgrushka@uic.edu Pain Res Manag. Fall 2003; 8 (3): 133-5. Burning mouth syndrome and other oral sensory disorders: a unifying hypothesis.   - Zakrzewska JM, Forsell H, Glenny AM. J Orofac Bread. Fall 2003; 17 (4): 293-300. Interventions for the treatment of burning mouth syndrome: a systematic review.   1) Use of an extract of Tephrosia purpurea for the preparation of a pharmaceutical or dermatological composition for the prevention and / or treatment of stomatodynia.   2) Use according to claim 1, characterized in that said composition is intended for the prevention and / or treatment of psychogenic stomatodynies.   3) Use according to one of claims 1 or 2, characterized in that said extract is an extract rich in amino acids, oligopeptides and oligosaccharides.   4) Use according to one of claims 1 to 3, characterized in that said pharmaceutical composition is a mouthwash.   5) Use according to any one of the preceding claims, characterized in that said composition comprises about 10% by weight of the extract, water and optionally at least one acceptable excipient.