TRANSDERMAL PATCHES FOR USE IN AURICULOTHERAPY

Abstract

A transdermal patch for use in auriculotherapy containing at least one active substance selected from caffeine, chocolate and glutamine for the modulation of neurotransmitters. The transdermal patch contains at least one ingredient selected from L-tyrosine, phenylalanine, 5-htp decarboxylase, 5-hydroxy-tryptophane, tryptophan, theobromine, anandamide, phenylethylamine, gamma hydroxybutyrate acid, gamma hydroxybutyric acid, GABA transaminase, theanine, taurine, homotaurine, melatonin, carnitine, acetyl-carnitine, S-Adenosylmethionine, N-acetyl L-cysteine, N-acetyl-transferase, phosphatidylserine, inositol, phosphatidylinositol, catalase, dopamine beta-hydroxylase, L-dopa descarboxylase, NADH, magnesium, zinc, manganese, chromium, copper, selenium, iron, calcium, lithium, calcium citrate, vitamin C, vitamin B, coenzyme Q10, omega-3, ashwagandha, Melissa oficinalis, Siberian ginseng, St. John's wort, valerian, Ginko biloba, Mucuna pruriens, turmeric, Rhodiola rosea and Bacopa monniera extracts.

Claims

1. A transdermal patch for use in auriculotherapy comprising at least one active substance selected from the group consisting of caffeine, chocolate and glutamine for a modulation of neurotransmitters.

2. The patch, according to claim 1, characterized also in that it comprises at least one further ingredient or cofactor selected from the list comprising L-tyrosine, phenylalanine, 5-htp decarboxylase, 5-hydroxy-tryptophane, tryptophan, theobromine, anandamide, phenylethylamine, gamma hydroxybutyrate acid, gamma hydroxybutyric acid, GABA transaminase, theanine, taurine, homotaurine, melatonin, carnitine, acetyl-carnitine, S-Adenosylmethionine, N-acetyl L-cysteine, N-acetyl-transferase, phosphatidylserine, inositol, phosphatidylinositol, catalase, dopamine beta-hydroxylase, L-dopa descarboxylase, NADH, magnesium, zinc, manganese, chromium, copper, selenium, iron, calcium, lithium, calcium citrate, vitamin C, vitamin B, coenzyme Q10, omega-3, ashwagandha, Melissa oficinalis, Siberian ginseng, St. John's wort, valerian, Ginko biloba, Mucuna pruriens, turmeric, Rhodiola rosea and Bacopa monniera extracts, or a combination thereof.

3. The patch, according to claim 1, characterized in that said active substances are present at a concentration between 1% by weight and 90% by weight, relative to the total of components.

4. The patch according to claim 1, characterized in that said active substances are present at an amount ranging from 0.01 and 1000 mg.

5. The patch according to claim 4, characterized in that said active substances are present at an amount ranging from 0.1 and 750 mg.

6. The patch according to claim 2, characterized in that said further ingredient or cofactor is present at a concentration ranging between 1% by weight and 90% by weight relative to the total of components.

7. The patch according to claim 2, characterized in that said further ingredient or cofactor is present at a concentration ranging between 0.01 and 1000 mg.

8. The patch according to claim 1, characterized in that it comprises the following structural elements: a deposit containing at least one active substance, a release controlling system, an adhesive surface for fixing the patch to the skin, and/or a film or protective covering.

9. The patch according to claim 8, characterized in that said adhesive surface acts likewise as a deposit containing the at least one active substances.

10. The patch according to claim 1, characterized in that it comprises an outer layer of tissue containing alternating copper and zinc voltaic cells, an adhesive layer or surface containing the at least one active substance, and it is applied by passive iontophoresis.

11. The patch according to claim 1, characterized in that its total area ranges between 10 and 200 mm.sup.2.

12. The patch according to claim 11, characterized in that said total area ranges between 50 and 100 mm.sup.2.

13. The patch , according to claim 1, for use in the treatment of physiological, neurological and neurohormonal disorders.

14. The patch according to claim 13, characterized in that said physiological, neurological and neurohormonal disorder is selected from mood disorders, such as depression or depressive mood, eating disorders such as bulimia and anorexia, disorders involving addiction to toxic substances, mental disorders such as schizophrenia, neurological diseases such as Parkinson's, appetite regulation and overweight control, increase of libido and regulation of prolactin levels, regulation of motor activity and cognitive functions, of learning and memory, for treating attention deficits, for enhancing motivation and problem resolution, for the treatment of pain as anaesthetic, to control nausea and vomiting and even to improve immunity, for insomnia, to control panic attacks, stress, aggressiveness, tobacco use, headaches and migraines, for regulating circadian rhythm, gastrointestinal movement and neuroendocrine functions, for the treatment of irritable bowel, pain in chronic cases such as fibromyalgia, post-traumatic stress, or promoting peacefulness and well-being.

15. The patch according to claim 13, characterized in that said treatment lasts between 2 weeks and 18 months.

Description

EXAMPLES

Example 1: Preparation of the Transdermal Patches for Auriculotherapy Containing an Active Substance According to the Present Invention

[0094] Square-shaped transdermal patches of a size of 100 mm.sup.2 comprising three layers were prepared: a layer containing the release controlling system, a silicone adhesive layer containing the deposit for the active substance, and a protective occlusive layer.

[0095] Four different active substances were used for the manufacture of four different types of transdermal patches: caffeine, chocolate (dark powder type), tryptophan and glutamine. [0096] a) A solution containing a final concentration of 600 mg/ml of caffeine was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was attached on one side to the release controlling system layer and sealed on the other side with the protective occlusive layer. [0097] b) A solution containing a final concentration of 750 mg/ml of dark chocolate powder was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was attached on one side to the release controlling system layer and sealed on the other side with the protective occlusive layer. [0098] c) A solution containing a final concentration of 100 mg/ml tryptophan was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was attached on one side to the release controlling system layer and sealed on the other side with the protective occlusive layer. [0099] d) A solution containing a final concentration of 500 mg/ml of glutamine was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was attached on one side to the release controlling system layer and sealed on the other side with the protective occlusive layer.

[0100] The patches were stored in containers of 30 patches each and their stability at room temperature was checked from 6 to 36 months.

Example 2: Preparation of the Transdermal Patches for Auriculotherapy Containing Two Active Substances According to the Present Invention

[0101] Square-shaped transdermal patches of a size of 50 mm.sup.2 comprising three layers were prepared: a layer containing the release controlling system, a polyacrylate adhesive layer containing the deposit for the active substances, and a protective occlusive layer.

[0102] Two groups of different active substances were used for the manufacture of transdermal patches of combined action for auriculotherapy: a) chocolate (of the dark powder type) and tryptophan, and b) defatted cocoa powder, tryptophan and magnesium. [0103] a) A solution containing a final concentration of 750 mg/ml of dark chocolate powder and 100 mg/ml of tryptophan was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was attached on one side to the release controlling system layer and sealed on the other side with the protective occlusive layer. [0104] b) A solution containing a final concentration of 450 mg/ml of defatted cocoa powder, 150 mg/ml of tryptophan and 45 mg/ml of magnesium solvent was prepared in the appropriate. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was attached on one side to the release controlling system layer and sealed on the other side with the protective occlusive layer.

[0105] The patches were stored in containers of 30 patches each and their stability at room temperature was checked from 6 to 36 months.

Example 3: Preparation of the Transdermal Patches for Auriculotherapy Containing an Active Substance and a Cofactor According to the Present Invention

[0106] Square-shaped transdermal patches of a size of 75 mm.sup.2 comprising three layers were prepared: a polyacrylate adhesive layer containing the deposit for the active substances and the release controlling system, and a protective occlusive layer.

[0107] The following groups of active substances and different cofactors were used for the manufacture of transdermal patches for auriculotherapy: a) caffeine and vitamin C, b) dark chocolate powder and magnesium, c) tryptophan and magnesium, and d) glutamine and inositol. [0108] a) A solution containing a final concentration of 500 mg/ml of caffeine and 250 mg/ml of vitamin C was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was sealed on the other side with the protective occlusive layer. [0109] b) A solution containing a final concentration of 700 mg/ml of dark chocolate powder and 200 mg/ml of magnesium was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was sealed on the other side with the protective occlusive layer. [0110] c) A solution containing a final concentration of 250 mg/ml tryptophan and 100 mg/ml magnesium was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was sealed on the other side with the protective occlusive layer. [0111] d) A solution containing a final concentration of 500 mg/ml of glutamine and 100 mg/ml of inositol was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was sealed on the other side with the protective occlusive layer.

[0112] The patches were stored in containers of 30 patches each and their stability at room temperature was checked from 6 to 36 months.

Example 4: Preparation of the Transdermal Patches for Auriculotherapy Containing an Active Substance or a Combination of an Active Substance and a Cofactor, by Passive Iontophoresis According to the Present Invention

[0113] Square-shaped transdermal patches of a size of 100 mm.sup.2 comprising two layers were prepared: a polyacrylate adhesive layer containing the deposit for the active substance alone or in combination with a cofactor, and a protective layer containing the alternating voltaic cells of Copper and Zinc.

[0114] As active substances, caffeine, dark chocolate powder, tryptophan and glutamine and as cofactors respectively vitamin C, magnesium, magnesium again, and inositol were used for the manufacture of transdermal patches for auriculotherapy by passive iontophoresis. [0115] a) A solution containing a final concentration of 500 mg/ml of caffeine was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said layer was sealed with the protective layer. [0116] b) A solution containing a final concentration of 750 mg/ml of dark chocolate powder was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said layer was sealed with the protective layer. [0117] c) A solution containing a final concentration of 250 mg/ml tryptophan was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said layer was sealed with the protective layer. [0118] d) A solution containing a final concentration of 450 mg/ml of glutamine was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said layer was sealed with the protective layer. [0119] e) A solution containing a final concentration of 500 mg/ml of caffeine and 250 mg/ml of vitamin C was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said layer was sealed with the protective layer. [0120] f) A solution containing a final concentration of 700 mg/ml of dark chocolate powder and 500 mg/ml of magnesium was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said layer was sealed with the protective layer. [0121] g) A solution containing a final concentration of 250 mg/ml tryptophan and 100 mg/ml magnesium was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said layer was sealed with the protective layer. [0122] h) A solution containing a final concentration of 500 mg/ml of glutamine and 100 mg/ml of inositol was prepared in the appropriate solvent. 1 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said layer was sealed with the protective layer.

[0123] The patches were stored in containers of 30 patches each and their stability at room temperature was checked from 6 to 24 months.

Example 5: Preparation of the Transdermal Patches for Application on the Arm Containing an Active Substance According to the Prior Art

[0124] Transdermal patches for application in the patient's arm according to the prior art were prepared. Said patches, rectangular and with a size of 10 cm.sup.2, comprised three layers: a polyacrylate adhesive layer containing the deposit for the active substances and the release controlling system, and a protective occlusive layer.

[0125] The same active substances used for the transdermal patches for auriculotherapy of the present invention were used for the manufacture of three transdermal patches according to the prior art and: caffeine, dark chocolate powder, tryptophan and glutamine. [0126] a) A solution containing a final concentration of 300 mg/ml of caffeine was prepared in the appropriate solvent. 2 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was attached on one side to the release controlling system layer and sealed on the other side with the protective occlusive layer. [0127] b) A solution containing a final concentration of 375 mg/ml of dark chocolate powder was prepared in the appropriate solvent. 2 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was attached on one side to the release controlling system layer and sealed on the other side with the protective occlusive layer. [0128] c) A solution containing a final concentration of 50 mg/ml tryptophan was prepared in the appropriate solvent. 2 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was attached on one side to the release controlling system layer and sealed on the other side with the protective occlusive layer. [0129] d) A solution containing a final concentration of 250 mg/ml glutamine was prepared in the appropriate solvent. 2 ml of said solution was added to the deposit located in the adhesive layer and was allowed to dry. Subsequently, said adhesive layer was attached on one side to the release controlling system layer and sealed on the other side with the protective occlusive layer.

Example 6: Comparative Study of a Treatment with the Transdermal Patches by Auriculotherapy According to the Present Invention Compared to a Treatment with Transdermal Patches According to the Prior Art, for the Treatment of Carbohydrate Abuse (Sugars)

[0130] A total of 18 patients aged between 45 and 55, diagnosed with obesity due to abuse of carbohydrates (sugars) through anamnesis and initial urinalysis, which showed low levels of serotonin (between 90 and 120 μg/24 h), slightly low levels of dopamine (between 100 and 118 μg/24 h), and slightly high levels of GABA (between 4.8 and 5.5 μg/24 h), were treated with the transdermal chocolate patches as described below.

[0131] The patients were divided into the following groups: [0132] Group I: 3 patients were treated with transdermal patches containing chocolate, such as those described in example 1b), using the auriculotherapy technique. [0133] Group II: 3 patients were treated with transdermal patches of chocolate and magnesium, such as those described in example 3b), using the auriculotherapy technique. [0134] Group III: 3 patients were treated with transdermal patches of chocolate by iontophoresis, such as those described in example 4b), using the auriculotherapy technique. [0135] Group IV: 3 patients were treated with transdermal patches of chocolate and magnesium by iontophoresis, such as those described in example 4f), using the auriculotherapy technique. [0136] Group V: 3 patients were treated with transdermal patches of chocolate applied on the arm, such as those described in example 5b). [0137] Group VI: 3 patients were treated with transdermal patches that did not contain any active substances, but were manufactured in a manner similar to the patches of Example 1.

[0138] The 18 patients were treated with the transdermal patch of chocolate indicated for their group for a period of seven weeks. Each patient had a patch placed on the auricle or arm, as appropriate, which was maintained during the seven weeks of the treatment. The aim of the therapeutic approach was to increase serotonin levels and consequently, increase the slightly reduced levels of dopamine and decrease the slightly high levels of GABA.

[0139] After seven weeks of treatment, the availability of serotonin and dopamine within the presynaptic vesicles was checked by means of a new urine test. The average results obtained for each of the groups are the following:

TABLE-US-00001 Group I Group II Group III Group IV Group V Group VI Serotonin 165−184 170−193 175−201 192−225 95−103 89−119 (μg/24 h) Dopamine 135−165 145−163 150−172 150−175 105−130 100−120 (μg/24 h) GABA 4−4.6 3.9−4.2 2.1−3.8 3−4.1 4.9−5.5 5−5.6 (μg/24 h)

[0140] The results obtained in urine tests revealed the efficacy of the transdermal patches for auriculotherapy of the present invention. Thus, the groups treated with the auriculotherapy patches according to the present invention with at least chocolate as active substance (groups I to IV) shown an increase in the levels of serotonin and dopamine in urine, as well as a decrease below 4.5 μg/24 h of GABA levels. In addition, the levels of serotonin and dopamine were slightly higher in groups III and IV, which were treated with transdermal patches for auriculotherapy using iontophoresis, as compared with the groups treated with transdermal patches for auriculotherapy without iontophoresis.

[0141] In addition, the recovery of all patients in groups I, II, Ill and IV was noted in the clinical consultation, and their signs of anxiety about the abusive consumption of carbohydrates (sugars) were no longer present. However, only one patient in group V perceived improvement in symptoms and none of the patients in control group VI experienced changes during treatment.

[0142] No side effects associated with the transdermal patches for auriculotherapy according to the present invention were shown in any of the groups, and only one of the patients of group V indicated discomfort by wearing a large transdermal patch visible on the arm.

Example 7: Comparative Study of a Treatment with the Transdermal Patches by Auriculotherapy According to the Present Invention Compared to a Treatment with Transdermal Patches According to the Prior Art, for the Treatment of Mild Depression

[0143] A total of 18 patients aged between 25 and 35, diagnosed with mild depression through anamnesis and initial urinalysis, which showed low levels of serotonin (between 90 and 115 μg/24 h), low levels of dopamine (between 85 and 115 μg/24 h), and high levels of GABA (between 7.3 and 14 μg/24 h), were treated with the transdermal patches as described below.

[0144] In this case, a combined treatment of patches containing chocolate for seven weeks with patches containing caffeine for the subsequent four weeks was chosen.

[0145] The patients were divided into the following groups: [0146] Group I: 3 patients were first treated with transdermal patches of chocolate, such as those described in example 1b), and subsequently with transdermal patches of caffeine, such as those described in example 1 a), both using the auriculotherapy technique. [0147] Group II: 3 patients were treated with transdermal patches of chocolate and magnesium, such as those described in example 3b), and subsequently with transdermal patches of caffeine and vitamin C, such as those described in example 3a), both by the auriculotherapy technique. [0148] Group III: 3 patients were first treated with transdermal patches of chocolate by iontophoresis, such as those described in example 4b), and subsequently with transdermal patches of caffeine by iontophoresis, such as those described in example 4a), both using the auriculotherapy technique. [0149] Group IV: 3 patients were first treated with transdermal patches of chocolate and magnesium by iontophoresis, such as those described in example 4f), and subsequently with transdermal patches of caffeine and vitamin C by iontophoresis, such as described in example 4e), both using the auriculotherapy technique. [0150] Group V: 3 patients were first treated with transdermal patches of chocolate, applied on the arm, such as those described in example 5b) and subsequently with transdermal patches of caffeine applied on the arm, such as those described in example 5a). [0151] Group VI: 3 patients were first treated with transdermal patches that did not contain any active substances but were manufactured in a manner similar to the patches of Example 1.

[0152] In the first part of the treatment, the 18 patients were treated with the transdermal patch of chocolate indicated for their group for a period of seven weeks. Each patient had a patch placed on the auricle or arm, as appropriate, which was maintained during the seven weeks of the first part of the treatment. The aim of the therapeutic approach was to increase serotonin levels to increase dopamine levels accordingly.

[0153] In the second part of the treatment, the 18 patients were treated with the transdermal patch of caffeine indicated for their group for a period of four weeks, in order to regulate the dopamine levels.

[0154] After four weeks of this second part of the treatment, the availability of serotonin and dopamine within the presynaptic vesicles was checked by means of a new urine test. The average results obtained for each of the groups were the following:

TABLE-US-00002 Group I Group II Group III Group IV Group V Group VI Serotonin 175−199 182−201 188−219 197−225 100−120 92−115 (μg/24 h) Dopamine 125−155 130−168 150−172 162−175 89−122 85−113 (μg/24 h) GABA 3.5 3.7−4.7 3−3.9 3−4 6.5−8 6−12 (μg/24 h)

[0155] The results obtained in urine tests revealed the efficacy of the transdermal patches for auriculotherapy of the present invention. Thus, the groups that were treated first with the patches of chocolate and subsequently of caffeine (groups I to IV) for auriculotherapy according to the present invention, all presented an increase in the levels of serotonin and dopamine in urine, as well as a decrease below 4.5-5 μg/24 h of GABA levels. In addition, the levels of serotonin and dopamine were slightly higher in groups III and IV, which were treated with transdermal patches for auriculotherapy using iontophoresis, as compared with the groups treated with transdermal patches for auriculotherapy without iontophoresis.

[0156] In addition, the recovery of all patients in groups I, II, III and IV was noted in the clinical consultation, and their signs and symptoms of depression were no longer present. However, none of the patients in group V or control group VI experienced changes in their mood during treatment.

[0157] None of the groups showed side effects associated with the transdermal patches for auriculotherapy according to the present invention.

Example 8: Comparative Study of a Treatment with the Transdermal Patches by Auriculotherapy According to the Present Invention Compared to a Treatment with Transdermal Patches According to the Prior Art, for the Treatment of Anxiety and Insomnia

[0158] A total of 24 patients aged between 35 and 50, diagnosed with anxiety and insomnia through anamnesis and initial urinalysis, which showed imbalances in neurotransmitter levels, with low levels of serotonin (between 90 and 115 μg/24 h), high levels of dopamine (between 280 and 500 μg/24 h) and high levels of GABA (between 16.7 and 30 μg/24 h), were treated with the transdermal patches as described below.

[0159] In this case, a treatment with patches containing chocolate for eight weeks and with patches containing glutamine for three more weeks was chosen.

[0160] The patients were divided into the following groups: [0161] Group I: 4 patients were first treated with transdermal patches containing chocolate, such as those described in example 1b), and subsequently with transdermal glutamine patches, such as those described in example 1d), both using the auriculotherapy technique. [0162] Group II: 4 patients were first treated with transdermal patches of chocolate and magnesium, such as those described in example 3b), and subsequently with transdermal patches of glutamine and inositol, such as those described in the 3d example), both using the auriculotherapy technique. [0163] Group III: 4 patients were first treated with transdermal patches of chocolate by iontophoresis, such as those described in example 4b), and subsequently with transdermal patches of glutamine by iontophoresis, such as those described in example 4d), both using the auriculotherapy technique. [0164] Group IV: 4 patients were first treated with transdermal patches of chocolate and magnesium by iontophoresis, such as those described in example 40, and subsequently with transdermal patches of glutamine and inositol by iontophoresis, such as those described in example 4h), both using the auriculotherapy technique. [0165] Group V: 4 patients were first subjected to a treatment with transdermal patches of chocolate, applied on the arm, such as those described in example 5b) and subsequently with transdermal patches of glutamine applied on the arm, such as those described in example 5d). [0166] Group VI: 4 patients were treated with transdermal patches that did not contain any active substances but were manufactured in a manner similar to the patches of example 1.

[0167] The 24 patients treated with the transdermal patch of chocolate indicated for their group for a period of eight weeks. Each patient had a patch placed on the auricle or arm, as appropriate, which was maintained during the eight weeks of the treatment. The aim of the therapeutic approach was to reduce the level of dopamine by increasing serotonin.

[0168] In the second part of the treatment, the 24 patients were treated with the transdermal glutamine patch indicated for their group for a period of three weeks to regulate the GABA levels.

[0169] After the last three weeks, the availability of serotonin and dopamine within the presynaptic vesicles was checked by means of a new urine test. The average results obtained for each of the groups are the following:

TABLE-US-00003 Group I Group II Group III Group IV Group V Group VI Serotonin 170−185 178−195 193−222 200−225 99−127 90−115 (μg/24 h) Dopamine 162−175 150−169 142−155 125−139 247−328 300−450 (μg/24 h) GABA 4−4.8 3.9−4.9 2.5−3.5 3.5−4.5 12−19 16−30 (μg/24 h)

[0170] The results obtained in urine tests revealed the efficacy of the transdermal patches for auriculotherapy of the present invention. Thus, the groups that were treated with the patches of chocolate and glutamine for auriculotherapy (groups Ito IV) all presented an increase in the serotonin levels and a decrease in the urine dopamine levels, as well as a decrease below 4 μg/24 h of GABA levels. In addition, the levels of serotonin and dopamine in groups III and IV were slightly higher and slightly lower, respectively, for these groups, which were treated with transdermal patches for auriculotherapy by iontophoresis, as compared with the groups treated with transdermal patches without iontophoresis.

[0171] In addition, the recovery of all patients in groups I, II, III and IV was noted in the clinical consultation, and their signs and symptoms of anxiety had improved and experienced better sleep quality and duration. However, only two patients in group V perceived a slight improvement in their sleep, but none of the patients in control group VI experienced improvement with respect to their anxiety during treatment.

[0172] No side effects associated with the transdermal patches for auriculotherapy according to the present invention were shown in any of the groups and two patients of group V indicated discomfort by wearing a large transdermal patch visible on the arm.