Combination comprising spirulina and palmitoylethanolamide and/or salts or pharmaceutically acceptable derivatives thereof and their formulations, for use in the prevention and/or in the treatment of hyperactivated tissue conditions

Abstract

The present invention relates to the combination of spirulina and palmitoylethanolamide (PEA) and/or pharmaceutically acceptable derivates or salts thereof, pharmaceutical formulations comprising the combination of spirulina and PEA and/or pharmaceutically acceptable derivates or salts thereof, optionally together with at least one physiologically acceptable excipient, and the use of the combination of spirulina and PEA and/or pharmaceutically acceptable derivates or salts thereof and formulations which include the said combination, for use in the prevention and/or treatment of tissue hyperactivation states, in the prevention and/or treatment of inflammatory pathologies, in the prevention and/or treatment of alterations in cardiac and/or coronary tissue, in the prevention and/or treatment of alterations in the vascular tissue, in the prevention and/or treatment of ophthalmic pathologies, preferably in the prevention and/or treatment of macular degeneration pathologies and glaucoma, in the prevention and/or treatment of dyslipidemia, in the prevention and/or treatment of alterations in pulmonary tissue, in the prevention and/or treatment of alterations in pelvic tissues, in the prevention and/or treatment of cellular alterations due to carcinogenesis, and/or in the prevention and/or treatment of dermatological alterations.

Claims

1. A method of treating a condition selected from the group consisting of angina pectoris, macular degeneration, tinnitus, and peripheral neuropathy in a subject in need thereof, comprising administration of a combination comprising spirulina and palmitoylethanolamide, wherein the percentage of spirulina is between 35% and 70% of the combination and the percentage of palmitoylethanolamide is between 30% and 65% of the combination, alone or in combination with one or more physiologically acceptable excipients.

2. The method according to claim 1, wherein the condition is peripheral neuropathy.

3. The method according to claim 1, wherein the condition is tinnitus.

4. The method according to claim 2, wherein the subject is a diabetic patient.

5. The method according to claim 1, wherein the condition is angina pectoris.

6. A method of reducing creatine levels in a diabetic patient in need thereof, comprising administration of a combination comprising spirulina and palmitoylethanolamide, wherein the percentage of spirulina is between 35% and 70% of the combination and the percentage of palmitoylethanolamide is between 30% and 65% of the combination, alone or in combination with one or more physiologically acceptable excipients.

7. The method according to claim 1, wherein the condition is macular degeneration.

Description

DESCRIPTION

(1) Surprisingly, it has now been found that the combination of spirulina and palmitoylethanolamide (PEA) and/or pharmaceutically acceptable derivates or salts thereof can prevent and/or efficiently treat tissue hyperactivation states.

(2) In particular, the combination of spirulina and PEA is useful in the prevention and/or treatment of inflammatory pathologies, in the prevention and/or treatment of alterations in cardiac and/or coronary tissue, in the prevention and/or treatment of alterations in vascular tissue, in the prevention and/or treatment of ophthalmic pathologies, and preferably in the prevention and/or treatment of macular degeneration and/or glaucoma, in the prevention and/or treatment of dyslipidemia, in the prevention and/or treatment of alterations in pulmonary tissue, in the prevention and/or treatment of alterations in pelvic tissues, in the prevention and/or treatment of cellular alterations due to carcinogenesis, and/or in the prevention and/or treatment of dermatological alterations.

(3) One object of the present invention is therefore a combination comprising spirulina and PEA, and/or pharmaceutically acceptable derivates or salts thereof. Preferably, the spirulina used in the present invention is a dry extract.

(4) According to a preferred aspect, the percentage of spirulina and/or pharmaceutically acceptable derivates or salts thereof is between 10% and 90% of the combination, wherein the percentage of PEA and/or pharmaceutically acceptable derivates or salts is between 10% and 90% of the combination, wherein the said percentages refer to the total weight of the combination.

(5) Particularly preferred combinations are those comprising spirulina and PEA and/or pharmaceutically acceptable derivates or salts thereof wherein the percentages of spirulina and PEA in the combination are, respectively: 65% and 35%, or 55% and 45%, or 70% and 30%, or 35% and 65%, or 40% and 60%, wherein the said percentages refer to the total weight of the combination.

(6) A further object of the present invention consists of the combination comprising spirulina and PEA, and/or pharmaceutically acceptable derivates or salts thereof, for use in the prevention and/or treatment of tissue hyperactivation states, in the prevention and/or treatment of inflammatory pathologies, in the prevention and/or treatment of alterations in the central nervous system (CNS) and the peripheral nervous system (PNS), preferably in the degeneration of central nervous tissue, such as for example, tinnitus, and in degenerative pathologies, in the prevention and/or treatment of loss of cognitive ability due to degenerative and/or traumatic causes, in the prevention and/or treatment of disorders of the peripheral nervous system, as well as in the prevention and treatment of peripheral neuropathies, in the prevention and/or treatment of alterations in cardiac tissue and/or coronary, in the prevention and/or treatment of alterations in the vascular tissue, in the prevention and/or treatment of ophthalmic pathologies, preferably in the prevention and/or treatment of macular degeneration and glaucoma, in the prevention and/or treatment of dyslipidemia, in the prevention and/or treatment of alterations in pulmonary tissue, in the prevention and/or treatment of alterations in the renal tissue, in the prevention and/or treatment of alterations in the pelvic tissues, in the prevention and/or treatment of cellular alterations due to carcinogenicity, and/or in the prevention and/or treatment of dermatological alterations.

(7) The aforesaid alterations in cardiac tissue may be due to ischemia, heart attack, and/or surgical procedures in the past and/or in progress.

(8) The aforesaid alterations in coronary tissue may be due to stenosis, occlusions, hormonal alterations, tissue degeneration and/or surgical procedures in the past and/or in progress.

(9) The aforesaid alterations in vascular tissue may be due to infections, hormonal alterations, tissue degeneration and/or surgical procedures in the past and/or in progress.

(10) The aforesaid alterations in renal tissue may be due to infections, hormonal alterations, tissue degeneration and/or surgical procedures in the past and/or in progress.

(11) The aforesaid alterations in pulmonary tissue may be due to allergic processes, infections, tissue degeneration (including therein degeneration of oncological origin) in the past and/or in progress.

(12) The aforesaid alterations in tissue in the pelvic area may be due to allergic processes, infections, hormonal alterations, tissue degeneration and/or surgical procedures in the past and/or in progress.

(13) The aforesaid alterations in the central nervous system tissue may be due to degenerative processes, alterations in nerve conduction, alterations of oncological or hormonal origin, tissue degeneration, and/or surgical procedures in the past and/or in progress.

(14) The aforesaid alterations in the peripheral nervous system tissue may be due to degenerative processes, alterations in nerve conduction, alterations of oncological or hormonal origin, tissue degeneration, and/or surgical procedures in the past and/or in progress.

(15) The combination in the invention, as defined above, is useful for the treatment of alterations after the reperfusion of cardiac tissue following heart attacks, coronary occlusion, and/or surgical procedures.

(16) Without being bound to a particular theory, it is thought that the synergistic action of the combination comprising spirulina and PEA, and/or pharmaceutically acceptable derivates or salts thereof, is due both to the regulatory activity of the PEA in relation to the inflammatory process and that of the spirulina in relation to the immune system cells during the immune system cell hyperactivation processes, in the same way as occurs during the inflammatory processes.

(17) Spirulina may also provide the tissue cells involved in the hyperactivation with a series of elements such as protein, vitamins, fatty acids, minerals, etc. which can support the functional recovery of the tissue involved. The aforesaid tissue alterations may be acute or chronic and may be dermatological pathologies, such as atopic dermatitis, dermatomyositis, scleroderma, psoriasis, polymyositis, pemphigus, epidermolysis bullosa, and pemphigoid; ophthalmic pathologies, such as, for example. Sjogren's syndrome, sympathetic ophthalmia, uveitis, uveo-retinitis, macular degeneration, optic neuritis and glaucoma; mucosal pathologies, such as those of the gastrointestinal mucous membranes (Crohn's disease) and the oral and genital mucosa; articular and connective pathologies, such as rheumatoid arthritis, psoriatic arthritis, arthritis from lupus erythematosus, and discoid and systemic lupus erythematosus; pathologies, such as chronic solar dermatitis, asthma, and intestinal and pulmonary fibrosis, and chronic arthritis; degenerative pathologies of the peripheral nervous system (PNS) and central nervous system (CNS), such as multiple sclerosis, neurodegenerative pathologies (not only of the autoimmune variety), processes connected to the CNS, such as Parkinson's disease, senile dementia, bacterial meningitis, HIV infections, tinnitus, Meniere's syndrome, brain damage of ischemic or hemorrhagic origin and traumatic damage; pathologies of the PNS, such as radiculopathy of inflammatory origin; pathologies of the central and peripheral nervous system where the inflammatory processes follow the first ischemic insult, such as neuropathies due to compression, as well as traumatic neuropathies, cerebral strokes and cranial traumas; cardiological diseases deriving from perfusion phenomena as a consequence of ischemic injuries; pathologies associated with fibrosis, such as allergic conjunctivitis, giant papillary conjunctivitis, dietary allergies, abnormal cicatrisation, such as hypertrophic cicatrix, keloids, and ocular cicatricial pemphigoid; pathologies in which renal function is altered as a result of alterations in renal functions.

(18) In particular, the combination comprising spirulina and PEA, and/or pharmaceutically acceptable salts or derivates thereof, is for simultaneous, separate, or sequential use in the prevention and/or treatment of the aforesaid pathologies. In other words, the active ingredients of the combination envisaged in the invention may be administered simultaneously, separately, or sequentially. A further object of the present invention is a composition comprising the combination of spirulina and PEA and/or pharmaceutically acceptable derivates or salts thereof, optionally together with at least one physiologically acceptable excipient.

(19) The compositions comprising the combination of spirulina and PEA and/or pharmaceutically acceptable derivates or salts thereof, optionally together with at least one physiologically acceptable excipient, are suitable for use in the prevention and/or treatment of all the aforesaid pathologies for the combination of spirulina and PEA and/or pharmaceutically acceptable derivates or salts thereof. Preferably, the said combinations are for simultaneous, separate, or sequential use in the prevention and/or treatment of all the aforesaid pathologies.

(20) According to preferred embodiments of the present invention, the said compositions comprising the combination in the invention together with a pharmaceutically acceptable excipient are compositions which are administrable in oral, topical, otologic, ophthalmic, rectal, vaginal, or parenteral forms.

(21) Preferably, when the administration of the compositions in the invention is performed orally, the pharmaceutical form may be a tablet, capsule, granules, powder, oily capsule, solution or a suspension, and still more preferably, the said oral form may be a tablet, capsule, granules, or a solution.

(22) Preferably, when the administration of the compositions in the invention is performed topically, the pharmaceutical form may be a cream, ointment, gel, salve, solution, wash (solution or suspension), drops, buffer (buffer solution), suspension, eye drops, spray, wipe, or powder, and more preferably, the said topical form may be a cream, gel, spray, suppository, or an ointment.

(23) The topical forms of administration may also include otologic topical administration, and in this case the pharmaceutical form may be a wash, spray, drops, buffer or cream, and ophthalmic administration, in which case the pharmaceutical form may be eye drops, wash, wipe, or cream.

(24) Preferably, when the administration of the compositions in the invention is performed rectally, the pharmaceutical form may be a cream, suppository, or an enema.

(25) Preferably, when the administration of the compositions in the invention is performed vaginally, the pharmaceutical form may be a cream, pessary, wipe or a cannula.

(26) Preferably, when the administration of the compositions in the invention is performed parenterally, the pharmaceutical form may be an aqueous buffer solution or oily suspension capsule, and still more preferably, the said parenteral form may be an oily solution.

(27) Still more preferably, when the combination and/or the compositions according to the invention are used in the prevention and/or treatment of alterations in cardiac tissue, the following pharmaceutical forms are preferred: tablet, capsule, powder, solution, or wash.

(28) Still more preferably, when the combination and/or the compositions according to the invention are used in the prevention and/or treatment of alterations in vascular tissue, the following pharmaceutical forms are preferred: capsule, powder, solution, tablet, cream, gel, or ointment.

(29) Still more preferably, when the combination and/or the compositions according to the invention are used in the prevention and/or treatment of alterations in coronary tissue, the following pharmaceutical forms are preferred: capsule, powder, solution, or tablet.

(30) Still more preferably, when the combination and/or the compositions according to the invention are used in the prevention and/or treatment of alterations after reperfusion of cardiac tissue, the following pharmaceutical forms are preferred: capsule, powder, solution, or tablet.

(31) Still more preferably, when the combination and/or the compositions according to the invention are used in the prevention and/or treatment of dyslipidemia, the following pharmaceutical forms are preferred: capsule, powder, solution, or tablet.

(32) Still more preferably, when the combination and/or the compositions according to the invention are used in the prevention and/or treatment of cellular alterations, the following pharmaceutical forms are preferred: powder, solution, tablet, cream, ointment, pessary, suppository, or wash.

(33) Still more preferably, when the combination and/or the compositions according to the invention are used in the prevention and/or treatment of alterations in pulmonary tissue, the following pharmaceutical forms are preferred: capsule, powder, solution, tablet, or spray.

(34) Still more preferably, when the combination and/or the compositions according to the invention are used in the prevention and/or treatment of alterations in tissue in the pelvic area, the following pharmaceutical forms are preferred: capsule, powder, solution, tablet, wash, spray, cream, pessary, enema, gel or ointment.

(35) Still more preferably, when the combination and/or the compositions according to the invention are used in the prevention and/or treatment of alterations in central nervous system (CNS) tissue and/or peripheral nervous system (PNS) tissue, the following pharmaceutical forms are preferred: capsule, powder, solution, tablet, wash, spray, cream, pessary, enema, gel or ointment.

(36) Still more preferably, when the combination and/or the compositions according to the invention are used in the prevention and/or treatment of alterations in renal tissue, the following pharmaceutical forms are preferred: capsule, powder, solution, tablet, wash, spray, cream, pessary, enema, gel or ointment.

(37) According to a preferred embodiment of the present invention, the formulations comprising the combination of spirulina and palmitoylethanolamide (PEA) and/or pharmaceutically acceptable derivates or salts thereof, optionally together with at least one physiologically acceptable excipient, are administered daily.

(38) According to a preferred aspect, the daily administration envisages one to four doses per day, even more preferably two or four daily doses, wherein the said doses preferably contain from 0.1 to 90 mg of the combination in the invention per kg of the patient's body weight, and still more preferably from 0.5 to 50 mg per kg of the patient's body weight.

(39) According to a further preferred aspect of the invention, daily administration is continued for a period of at least 15 days, preferably of at least 30 days, and still more preferably of at least 90 days. According to a further preferred aspect, such administration is continued for a period of at least 35 days, preferably for at least 65 days.

(40) According to a still further preferred embodiment of the present invention, the composition in the invention is administered orally, preferably in the form of a tablet or capsule, twice or four times a day, for a period of at least 15 days, preferably at least 30 days, and still more preferably, at least 90 days. According to a further preferred aspect, such administration is continued for a period of at least 35 days, preferably for at least 65 days.

(41) According to a further preferred aspect, each of the aforesaid tablets comprises from 200 to 700 mg of PEA and from 300 to 800 mg of spirulina, and more preferably comprises 300, 350, 450, 600 or 650 mg of PEA and 350, 400, 550, 650 or 700 mg of spirulina.

(42) Still more preferably, the aforesaid tablets contain 350 mg of PEA and 650 mg of spirulina, or they contain 450 mg of PEA and 550 mg of Spirulina, or they contain 300 mg of PEA and 700 mg of spirulina, or they contain 650 mg of PEA and 350 mg of spirulina, or they contain 600 mg of PEA and 400 mg of spirulina.

Example 1

(43) A clinical study was performed to test the synergistic effect of the combination of spirulina (used as dry extract) and palmitoylethanolamide (PEA) in the treatment of tinnitus.

(44) In the study, six patients were treated, comprising both men and women, with a mean age of 49.6 years (50-year-old woman, 46 year-old man, 38 year-old man, 46 year-old woman, 53 year-old man, 65 year-old women), who had been suffering from tinnitus for at least one year.

(45) The patients were divided into three groups and, in accordance with the present invention, were treated according to the following schema: the patients in the first group (aged 46 to 50 years) were treated with two tablets, each comprising 350 mg of PEA, administered twice a day, for a daily total of 1,400 mg of PEA, for a duration of S days; next, the same patients were treated with one tablet, comprising 350 mg of PEA, administered twice a day, for a daily total of 700 mg of PEA, for a duration of 10 days; the patients in the second group (aged 38 to 53 years) were treated with two tablets, each comprising 650 mg of spirulina, administered twice a day, for a daily total of 2,600 mg of spirulina, for a duration of 5 days; next, the same patients were treated with one tablet, comprising 650 mg of spirulina, administered twice a day, for a daily total of 1,300 mg of spirulina, for a duration of 10 days; the patients in the third group (aged 46 to 65 years) were treated with two tablets, each comprising 650 mg of spirulina and 350 mg of PEA, administered twice a day, for a daily total of 2,600 mg of spirulina combined with 1,400 mg of PEA, for a duration of 5 days; next, the same patients were treated with one tablet, comprising 650 mg of spirulina and 350 mg of PEA, administered twice a day, for a daily total of 1,300 mg of spirulina combined with 700 mg of PEA, for a duration of 10 days;

(46) All the patients received the products for the period stated.

(47) At the examination after the treatment, neither the two patients treated with PEA, nor the two patients treated with spirulina showed variations in the tinnitus, while the two patients treated with the combination of spirulina and PEA (where the spirulina totaled 65% of the combination and the PEA 35%) showed a marked and significant improvement in the tinnitus perceived, with an approximately 65% reduction in the tinnitus and a marked improvement in hearing. The improvements regarding the tinnitus were declared by patients, while the improvement in hearing was measured via an audiometric test, carried out before and after administration of the combination in the invention. It is particularly significant that the 65% reduction in tinnitus was obtained among patients who had been suffering from the pathology for a long time.

(48) The synergistic effect of the combination of spirulina and PEA in the treatment of tinnitus has therefore been demonstrated, in particular where the combination comprises 65% spirulina and 35% PEA.

Example 2

(49) A clinical study was performed to test the synergistic effect of the combination of spirulina (used as dry extract) and PEA in the treatment of senile macular degeneration.

(50) In the study, three patients were treated, comprising both men and women, aged 56 years, 65 years and 62 years, who were suffering from age-related macular degeneration with the presence of macular drusen, i.e. localised deposits between the retinal pigment epithelium (RPE) and the Bruch membrane, together with geographic atrophy, characterised by RPE cell death and atrophy of the overlying photoreceptors.

(51) All the patients underwent an assessment with the Amsler test, prior to administration of the combination of spirulina and PEA. All three patients presented macular degeneration with distortion (metamorphopsia) or line breaks with an average degree of macular degeneration.

(52) In accordance with the present invention, the patients were treated according to the following schema: the first patient (65-year-old man) was treated with a tablet comprising 450 mg of PEA, administered four times a day, for a daily total of 1.800 mg of PEA, for a duration of 10 days; next, the same patient was treated with one tablet, comprising 450 mg of PEA, administered twice a day, for a daily total of 900 mg of PEA, for a duration of 30 days; the second patient (56-year-old woman) was treated with a tablet comprising 550 mg of spirulina, administered four times a day, for a daily total of 2,200 mg of spirulina, for a duration of 10 days; next, the same patient was treated with one tablet, comprising 550 mg of spirulina, administered twice a day, for a daily total of 1,100 mg of spirulina, for a duration of 30 days; next, the third patient (62-year-old man) was treated with one tablet, comprising 550 mg of spirulina and 450 mg of PEA, administered four times a day, for a daily total of 2,200 mg of spirulina combined with 1,800 mg of PEA, for a duration of 10 days; next, the same patient was treated with one tablet, comprising 550 mg of spirulina and 450 mg of PEA, administered twice a day, for a daily total of 1,100 mg of spirulina combined with 900 mg of PEA, for a duration of 30 days.

(53) All the patients received the products for the period stated.

(54) Following treatment, all the patients underwent a further Amsler test, which produced the following results: the patient undergoing treatment with PEA showed a slight improvement in the Amsler test result; the patient undergoing treatment with spirulina showed a very slight improvement in the Amsler test result; the patient undergoing treatment with the combination of spirulina and PEA (where the spirulina totaled 55% of the combination and the PEA 45%) showed a clear, marked improvement in the Amsler test result, with—furthermore—an improvement in sight.

(55) The synergistic effect of the combination of spirulina and PEA in the treatment of senile macular degeneration has therefore been demonstrated, in particular where the combination comprises 55% spirulina and 45% PEA.

Example 3

(56) A clinical study was performed to test the synergistic effect of the combination of spirulina (used as dry extract) and PEA in the treatment of angina pectoris (chest pain).

(57) In the study, three patients were treated, comprising both men and women, aged 67, 65, and 72 years, who suffered from praecordial pain of cardiac origin. Upon undergoing a stress ECG, all the patients presented anginal pain during the stress and all were undergoing specific treatments (antihypertensives, beta blockers), which—nevertheless—were unable to fully control the aforesaid symptoms.

(58) In accordance with the present invention, the patients were treated according to the following schema: the first patient (65-year-old woman) was treated with a tablet comprising 300 mg of PEA, administered four times a day, for a daily total of 1,200 mg of PEA, for a duration of 15 days; next, the same patient was treated with one tablet, comprising 300 mg of PEA, administered twice a day, for a daily total of 600 mg of PEA, for a duration of 30 days; the second patient (67-year-old man) was treated with a tablet comprising 700 mg of spirulina, administered four times a day, for a daily total of 2,800 mg of spirulina, for a duration of 15 days; next, the same patient was treated with one tablet, comprising 700 mg of spirulina, administered twice a day, for a daily total of 1,400 mg of spirulina, for a duration of 30 days; next, the third patient (72-year-old man) was treated with one tablet, comprising 700 mg of spirulina and 300 mg of PEA, administered four times a day, for a daily total of 2,800 mg of spirulina combined with 1,200 mg of PEA, for a duration of 15 days; next, the same patient was treated with one tablet, comprising 700 mg of spirulina and 300 mg of PEA, administered twice a day, for a daily total of 1,400 mg of spirulina combined with 600 mg of PEA, for a duration of 30 days.

(59) All the patients received the products for the period stated in addition to the treatments already underway.

(60) Following treatment, the patients produced the following results: the patient being treated solely with PEA showed no significant changes in condition with respect to prior to administration of the PEA, i.e. when stress was increased during the stress ECG, the patient presented praecordial pain of cardiac origin; the patient being treated solely with spirulina showed very slight changes in condition with respect to prior to administration of the spirulina, i.e. when stress was increased during the stress ECG, the patient presented a lesser degree of praecordial pain of cardiac origin; the patient being treated with the combination of spirulina and PEA (where the spirulina amounted to 70% of the combination and PEA amounted to 30%) showed a clearly improved capacity to endure the stress ECG, without the appearance of praecordial pain, with respect to prior to administration of the combination in the invention. In particular, the improved capacity to endure the stress demonstrates the functional recovery of the heart muscle, accompanied by a net reduction in pain symptoms.

(61) The synergistic effect of the combination of spirulina and PEA in the treatment of angina pectoris (chest pain) has therefore been demonstrated, in particular where the combination comprises 70% spirulina and 30% PEA.

Example 4

(62) A clinical study was performed to test the synergistic effect of the combination of spirulina (used as dry extract) and PEA in the treatment of peripheral neuropathy in diabetics.

(63) In the study, three patients were treated, comprising both men and women, aged 52, 58, and 62 years, who suffered from peripheral neuropathy of diabetic origin. All the patients presented the classic symptoms of peripheral neuropathy, i.e. the classic symptoms consisting of paraesthesias, the sensation of ‘walking on cotton wool’, insensitivity to heat and/or cold, etc., and all the patients were undergoing specific treatments to control glycaemic values, in particular oral hypoglycaemic agents. The patients' glycaemia was tested, both at the beginning and the end of the study, to see if taking the product influenced glycaemic control in any way. All the patients had mean fasting glycaemia values of approximately 140 to 165 mg/dl.

(64) In accordance with the present invention, the patients were treated according to the following schema: the first patient (52-year-old man) was treated with a tablet comprising 650 mg of PEA, administered four times a day, for a daily total of 2,600 mg of PEA, for a duration of 5 days; next, the same patient was treated with one tablet, comprising 650 mg of PEA, administered twice a day, for a daily total of 1,300 mg of PEA, for a duration of 30 days; the second patient (58-year-old woman) was treated with a tablet comprising 350 mg of spirulina, administered four times a day, for a daily total of 1,400 mg of spirulina, for a duration of 5 days; next, the same patient was treated with one tablet, comprising 350 mg of spirulina, administered twice a day, for a daily total of 700 mg of spirulina, for a duration of 30 days; next, the third patient (62-year-old man) was treated with one tablet, comprising 350 mg of spirulina and 650 mg of PEA, administered four times a day, for a daily total of 1,400 mg of spirulina combined with 2,600 mg of PEA, for a duration of 5 days; next, the same patient was treated with one tablet, comprising 350 mg of spirulina and 650 mg of PEA, administered twice a day, for a daily total of 700 mg of spirulina combined with 1,300 mg of PEA, for a duration of 30 days.

(65) All the patients received the products for the period stated.

(66) Following treatment, the patients produced the following results, which were assessed by measuring nerve conduction using a neurological tuning fork, biothesiometer, and via the Achilles reflex: the patient undergoing treatment solely with PEA showed a slight improvement in the neuropathic symptoms, without any influence on the glycaemic profile, and with a slight response to the biothesiometry test (glycaemic values remained constant, i.e. 140-160 mg/dl when fasting); the patient undergoing treatment solely with spirulina showed no changes in either the neuropathic condition or the glycaemic profile. Indeed, the initial assessment parameters with the tuning fork, the biothesiometer and the Achilles reflex test, remained unchanged, as did the glycaemic value, which was in the range of 155-160 mg/dl; the patient undergoing treatment with the combination of spirulina and PEA (where the spirulina totaled 35% of the combination and the PEA 65%) showed a clear improvement in the characteristic symptoms of peripheral neuropathy, with a clear improvement in nerve conduction and an improved glycaemic profile. In fact, the patient showed a marked improvement in nerve conduction when assessed with the tuning fork and the biothesiometer and a clear improvement in the Achilles reflex and glycaemic values showed an improvement, decreasing from a fasting value of 140-160 mg/dl to a fasting value of 130-140 mg/dl.

(67) The synergistic effect of the combination of spirulina and PEA in the treatment of peripheral neuropathy in diabetics has therefore been demonstrated, in particular where the combination comprises 35% spirulina and 65% PEA.

Example 5

(68) A clinical study was performed to test the synergistic effect of the combination of spirulina (used as dry extract) and PEA in the treatment of altered renal functions, preferably in diabetics.

(69) In the study, three patients were treated, comprising both men and women, aged 52, 58, and 62 years, who suffered from diabetes. All patients presented altered renal functions, evidenced by the creatinine value, i.e. a creatinine value of over 4 mg/dl (normal values range from 0.7 to 1.3 mg/dl). All the patients were undergoing specific treatments (conventional drugs, such as Decadurabolin, etc.) which, nevertheless, were unable to control the renal dysfunction. The patients' creatinine values were tested, both at the beginning and the end of the clinical study assessment.

(70) In accordance with the present invention, the patients were treated according to the following schema: the first patient (52-year-old man) was treated with a tablet comprising 650 mg of PEA, administered four times a day, for a daily total of 2,600 mg of PEA, for a duration of 5 days, next, the same patient was treated with one tablet, comprising 650 mg of PEA, administered twice a day, for a daily total of 1,300 mg of PEA, for a duration of 30 days; the second patient (58-year-old woman) was treated with a tablet comprising 350 mg of spirulina, administered four times a day, for a daily total of 1,400 mg of spirulina, for a duration of 5 days; next, the same patient was treated with one tablet, comprising 350 mg of spirulina, administered twice a day, for a daily total of 700 mg of spirulina, for a duration of 30 days; next, the third patient (62-year-old man) was treated with one tablet, comprising 350 mg of spirulina and 650 mg of PEA, administered four times a day, for a daily total of 1,400 mg of spirulina combined with 2,600 mg of PEA, for a duration of 5 days; next, the same patient was treated with one tablet, comprising 350 mg of spirulina and 650 mg of PEA, administered twice a day, for a daily total of 700 mg of spirulina combined with 1,300 mg of PEA, for a duration of 30 days.

(71) All the patients received the products for the period stated.

(72) After treatment, the patients showed the following creatinine values, which are indicative of renal functions: the patient undergoing treatment solely with PEA showed no improvement in renal functions, as the patient's creatinine values were: 4.3 mg/dl at the beginning of the treatment and 4.4 mg/dl at the end of the treatment; the patient undergoing treatment solely with spirulina showed no changes in the condition of the renal functions, as the patient's creatinine values were; 4.5 mg/dl at the beginning of the treatment and 4.6 mg/dl at the end of the treatment; the patient undergoing treatment with the combination of spirulina and PEA (where the spirulina amounted to 35% of the combination and the PEA amounted to 65%) showed a clear improvement in renal functions (renal filtering), as the patient's creatinine values were: 4.6 mg/dl at the beginning of the treatment and 4.1 mg/dl at the end of the treatment;

(73) The synergistic effect of the combination of spirulina and PEA in the treatment of altered renal functions, preferably in diabetic subjects, has therefore been demonstrated, in particular where the combination comprises 35% spirulina and 65% PEA.