Composition for treating retinal diseases
阅读说明：本技术 用于治疗视网膜疾病的组合物 (Composition for treating retinal diseases ) 是由 马尔切洛·桑托科诺 曼努埃拉·桑托诺奇托 克里斯蒂纳·扎普拉 卢卡·罗萨里奥·拉·罗萨 弗兰 于 2017-06-19 设计创作，主要内容包括：本发明涉及一种组合物,包含：虾青素、胡椒碱、乳香酸、辅酶Q10、姜黄、黄体素、玉米黄质、藏红花粉、铜以及可选的白藜芦醇、菠萝蛋白酶、锌、水杨苷和其他天然来源的抗氧化剂。本发明进一步涉及所述组合物用于治疗性质上是缺血性和/或退行性的视网膜疾病。(The present invention relates to a composition comprising astaxanthin, piperine, boswellic acid, coenzyme Q10, turmeric, lutein, zeaxanthin, saffron powder, copper and optionally resveratrol, bromelain, zinc, salicin and other antioxidants of natural origin the present invention further relates to the use of said composition for the treatment of retinal diseases which are ischemic and/or degenerative in nature.)
A composition comprises astaxanthin, piperine, boswellic acid, coenzyme Q10, curcumin, lutein, zeaxanthin, saffron powder, and copper.
2. The composition of claim 1, further comprising resveratrol, bromelain, zinc, salicin.
3. The composition of any of claim 1 or 2, comprising an additional natural antioxidant, preferably a polymeric anthocyanin.
4. The composition according to any of claims 1-3, comprising 0.1-200 mg of a concentrated extract of Haematococcus (Haematococcus sp.) containing not less than 2.0% astaxanthin, 0.01-15 mg of a piperine titer 95% of a dry extract obtained from the fruit of Piper nigrum (Piper nigrum), 10-2000 mg of an extract of the stems and fruits of Phoenix cinquefolius (Anneas comosus) having a total Boswellia titer of 70% and β of a Boswellia acid titer of 20%, 0-500 mg of a dry extract of the roots of Curcuma longa (Curcma longa) having a Gelatin Digestion Unit (GDU) equivalent of 1-1000, 0.5-100 mg of coenzyme Q10, 1-500 mg of a total curcumin titer 95% of Curcuma longa (Curcumaria longa), 0.1-250 mg of a extract of Huang 20% of a dry extract of Curcuma domestica (Coreanus sanguinea), 0.1-25 mg of a extract having a alcohol titer of 0.0-25% of a extract of purified extract of California (California extract from California), 0.0-25 mg of a extract from California extract having a alcohol titer of 0.0-25 mg of a extract of dry extract of Tagetol (Tagetes cornus extract, 0.0-25 mg of a extract of pure red sage extract, 0.0-25 mg of Crataegus extract from California extract of Crataceae extract of Crataegus (Tagetum extract, 0-25-2).
5. The composition of any of claims 1-4, comprising 1-100 mg of a concentrated extract of Haematococcus containing not less than 2.0% astaxanthin, 0.2-8 mg of a piperine titer 95% of a dry extract obtained from pepper fruits, 25-1000 mg of an extract of the gum resin of Lacca dentata having a total boswellic acid titer of 70% and β boswellic acid titer of 20%, 5-300 mg of an extract of the stems and fruits of pineapple containing bromelain equivalent to 8-480 Gelatin Digestive Units (GDU), 3-75 mg of coenzyme Q10, 10-250 mg of a dry extract of roots of turmeric having a total curcumin titer of 95%, 1-150 mg of an extract of flowers of Tagetes erecta having a voxel titer of 20%, 15-125 mg of a dry extract of blackcurrant having an Oxygen Radical Absorption Capacity (ORAC) of not less than 2mmol vitamin E equivalents per gram of extract, 0.3-0.75 mg of copper (from copper) oxide, 3-75 mg of a dry extract of Tagetes, 5-5 mg of purified extracts of Tagetes extracts from resveratrol (3-5, 5-25% of Tagetes).
6. The composition of any of claims 1-5, comprising 5-50 mg of a concentrated extract of Haematococcus containing not less than 2.0% astaxanthin, 0.75-4 mg of a piperine titer 95% of a dry extract obtained from the fruit of Piper nigrum, 50-600 mg of an extract of the gum resin of Lacca dentata having a total boswellic acid titer of 70% and β boswellic acid titer of 20%, 20-200 mg of an extract of the stems and fruits of pineapple containing bromelain equivalent to 15-370 Gelatin Digestive Units (GDU), 3-25 mg of coenzyme Q10, 30-100 mg of a dry extract of the roots of Curcuma longa having a total curcumin titer of 95%, 10-50 mg of an extract of the flowers of Tagetes erecta having a 20% lutein, 20-60 mg of a extract having an Oxygen Radical Absorption Capacity (ORAC) of not less than 2mmol vitamin E equivalents per gram of extract, 0.35-0.65 mg of copper (from copper (8 mg) of copper (from copper), 20mg of Tagetes having an Oxygen Radical Absorption Capacity (ORAC) from 2 mmol/g of the dry extract of Tagetes, 5-25 mg of Tagetes extracts of Tagetes, 2mg of purified extracts of Tagetes, 2-25 mg of Tagetes extracts of Tagetes (2-5-15) from Tagetes).
7. The composition of any of claims 1-6, wherein , comprises 10 to 30mg of a concentrated extract of Haematococcus containing not less than 2.0% astaxanthin, 1 to 3mg of a piperine titer 95% of a dry extract obtained from the fruit of Piper nigrum, 60 to 200mg of an extract of the gum resin of Lacca dentata having a total boswellic acid titer of 70% and β boswellic acid titer of 20%, 30 to 100mg of an extract of the stems and fruits of pineapple containing bromelain equivalent to 50 to 200 Gelatin Digestive Units (GDU), 4 to 12mg of coenzyme Q10, 30 to 70mg of a dry extract of the roots of Curcuma longa having a total curcumin titer of 95%, 15 to 35mg of an extract of the flowers of Tagetes erecta having a titer of 20%, 20 to 40mg of a dry extract of blackcurrant having an absorption capacity (ORAC) of not less than 2mmol vitamin E equivalents per gram of extract, 0.4 to 0.6mg of copper (from copper), 10 to 20mg of a dry extract of Tagetes having an absorption capacity (ORAC) of oxygen free radicals of not less than 2mmol of vitamin E equivalents per gram of extract, 5 to 90mg of purified extracts of Tagetes from resveratrol (5 to 5mg of Tagetes).
8. Composition according to of any one of claims 1 to 7, for use in the treatment of hydropsy and/or ischemic and/or degenerative retinal diseases, preferably selected from the group consisting of macular degeneration, diabetic retinopathy, retinal vein occlusion, central retinal vein occlusion, branch retinal vein occlusion, retinal arterial tree occlusion, central retinal artery occlusion, branch retinal artery occlusion, pore retinal degeneration, lattice or palisade degeneration, snail mucoid degeneration, degenerative retinal layer division, non-pore retinal degeneration, cystic degeneration, snowflake degeneration, pigmentary degeneration, alveolateral degeneration, peripheral drusen, oral pigmentary degeneration, hypertensive retinopathy, retinitis pigmentosa, maculopathy, stargardt disease, central serous chorioretinopathy.
9. The composition for use according to claim 7, wherein the use consists in nutritional support for the treatment of macular degeneration, diabetic retinopathy and macular edema.
10. The composition for use according to claim 8 or 9, wherein the composition is administered to a subject exposed to treatment with an anti-angiogenic agent.
11, nutritional formulations comprising the composition according to any of claims 1 to 6, and a pharmaceutically acceptable excipient for oral administration.
Technical Field
compositions comprising astaxanthin, piperine, boswellic acid (boswellic acid), coenzyme Q10, curcumin (curcuminids), lutein, zeaxanthin, saffron powder (saffron), copper, and optionally resveratrol, bromelain, zinc, salicin, and other natural sources of antioxidants are described herein the invention further relates to compositions for treating retinal diseases that are ischemic and/or degenerative in nature.
Background
The retina is the innermost and most differentiated of the 3 layers of capsule (tunic) that make up the wall of the eyeball, extending from the optic nerve to the pupillary margin of the iris. It has the function of receiving light stimuli and converting them into neural signals that are transmitted to brain structures.
From a histological point of view, the retina consists of two layers:
1. retinal pigment epithelium or outer leaf (outer leaf)
2. The nerve layer or inner lobe or the retina of the finger.
The retina is composed of several layers of cells and is divided into two regions: the central region, called macula, is rich in cone cells; and central and peripheral regions, in which rod cells predominate. The vascular system of the eye is ensured by two structurally and functionally independent systems, the retinal system and the ciliary system. Damage and disease that impair the normal structure or function of these pathways are the primary causes of vision impairment and blindness. For example, diabetic retinopathy is the most common disease affecting the retinal vasculature and is the leading cause of visual loss in people of working age.
Astaxanthin is an carotenoid, which can be extracted from various sources including Haematococcus ( species of green algae with high antioxidant capacity).
Piperine is an alkaloid present in pepper (pepper nigrum).
Boswellic acids were obtained from Boswellia serrata (Boswellia serrata).
Bromelain is present in the extract of pineapple (Ananas comosus) and comprises two proteolytic enzymes.
Coenzyme Q10 is a powerful antioxidant.
Curcumin is present in extracts of turmeric (Curcuma longa).
Lutein belongs to the xanthophyll group and can be extracted from various sources including flowers of marigold (Tagetes erecta).
Resveratrol is a polyphenol found in the skin of grapes and has been successfully extracted from various sources including the root of polygonum cuspidatum (polygonum cuspidatum).
Salicin is found in the salicaceae family and is β -glucoside with anti-Cox activity.
The stigma croci Sativi powder is extracted from stigma croci Sativi (Crocus sativus).
Zeaxanthin is a carotenoid of the lutein class and can be extracted from a variety of sources including flowers of marigold.
There remains an unmet need for supplemental treatment methods and compositions for retinal diseases the present invention satisfies this need.
Disclosure of Invention
compositions comprising natural extracts, carotenoids and minerals are described demonstrating that such compositions unexpectedly can protect the retina by promoting functional recovery under post-ischemic stress conditions.
Drawings
FIG. 1 comparison of ERG recordings relative to baseline at T3 and T7 of rats pretreated orally for 5 days by gavage of composition C or VHC (vehicle) according to the invention daily for times per day, IR induction after 1h and then for 7 days of treatment, Boa (A) and Bob (B). The data represent the mean and range of at least 4 animals per treatment group.p.ltoreq.0.05;. p.ltoreq.0.01;. p.ltoreq.0001; relative treatment benchmark.p.ltoreq.0.05. Holm-Amshid post-hoc tests after one-way ANOVA.
FIG. 2 Gene expression of TNF α in the retina of rats pretreated for 5 days daily times by gavage with composition C or VHC (vector) according to the invention after 1h IR induction and sacrificed 6h after ischemic event data are presented relative to calibrators
Detailed Description
In embodiments, the composition according to the invention comprises astaxanthin, piperine, boswellic acid, coenzyme Q10, curcumin, lutein, copper, saffron powder, zeaxanthin.
In an embodiment of step , the composition further comprises resveratrol, bromelain, zinc, and salicin.
In an embodiment of step , the composition comprises an additional antioxidant from a natural source.
More preferably, said other natural antioxidant is a polymeric anthocyanin derived from blackcurrant.
In embodiments, the composition comprises 0.1 to 200mg of a concentrated extract of the genus Haematococcus containing not less than 2.0% astaxanthin, 0.01 to 15mg of a piperine titer 95% of a dry extract obtained from the fruit of Piper nigrum, 10 to 2000mg of an extract of the gum resin of the Fraxinus dentata having a total titer of boswellic acid of 70% and β a total titer of 20%, 0 to 500mg of an extract of the stem and fruit of pineapple containing bromelain equivalent to 1 to 1000 Gelatin Digestive Units (GDU), 0.5 to 100mg of coenzyme Q10, 1 to 500mg of a dry extract of the root of Curcuma longa having a total curcumin titer of 95%, 0.1 to 250mg of an extract of the flower of Tagetes erecta having a titer of 20%, 0 to 500mg of an extract of Tagetes having an Oxygen Radical Absorption Capacity (ORAC) of not less than 2mmol of vitamin E trolox per gram of extract, 0.1 to 25mg of an extract of the root of Tagetes erecta, 0.5 to 500mg of an extract of purified extract of Tagetes (Salicornia) from Salicornia root of Salicornia extract, 0.5 to 150mg of a dry extract of Salicornia root of Salicornia (Salicornia extract of a root of a papyrium andra) from Salicornia, 0.5 to 150mg of a extract of a papyrifera, 0 to 150mg of a extract of a papyrifera, 0.5mg of a extract of a papyrifera, 0 to 150mg of a extract of a papyrifera, 0 to 10.
In an embodiment of step , the composition comprises 0.5 to 150mg of a concentrated extract of Haematococcus containing not less than 2.0% astaxanthin, 0.1 to 10mg of a piperine titer 95% of a dry extract obtained from the fruit of Piper nigrum, 20 to 1500mg of an extract of the gum resin of Lacca dentata having a total boswellic acid titer of 70% and β boswellic acid titer of 20%, 2 to 400mg of an extract of the stems and fruits of pineapple containing bromelain equivalent to 1 to 1000 Gelatin Digestive Units (GDU), 1 to 80mg of coenzyme Q10, 5 to 400mg of a dry extract of the roots of Curcuma longa having a total curcumin titer of 95%, 0.1 to 200mg of an extract of the flowers of Tagetes erecta having a titer of 20%, 0 to 250mg of an extract of Ribes nigrum having an Oxygen Radical Absorption Capacity (ORAC) of not less than 2 mmol/g, 0.25 to 0.75mg of an extract from copper (from copper sulfate), 0.5 to 5mg of a dry extract of Tagetes from 2 to 5mg of Tagetes (from 2 to 5mg of berberina extracts), 2 to 5mg of purified extracts of Tinospora tabacum carinica kola (2 to 10mg of zinc oxide, 2 to 5mg of 2 to 5).
In another embodiments, the composition comprises 1 to 100mg of a concentrated extract of the genus rhodococcus containing not less than 2.0% astaxanthin, 0.2 to 8mg of a piperine titer 95% of a dry extract obtained from the fruit of pepper, 25 to 1000mg of an extract of the gum resin of the mastic dentate tree having a total boswellic acid titer of 70% and β a total boswellic acid titer of 20%, 5 to 300mg of an extract of the stems and fruits of pineapple containing bromelain corresponding to 8 to 480 Gelatin Digestive Units (GDU), 3 to 75mg of coenzyme Q10, 10 to 250mg of a total curcumin titer 95% of a dry extract of the roots of turmeric, 1 to 150mg of an extract of the flowers of marigold having a lutein titer of 20%, 0 to 125mg of a dry extract of blackcurrant having an Oxygen Radical Absorption Capacity (ORAC) of not less than 2 mmol/g of extract, 0.3 to 0.75mg of copper (from copper esterified with 3), 0 to 125mg of a dry extract of the roots of resveratrol from 3 to 5mg of purified carica papaya (3 to 5mg of the roots of resveratrol) of the extracts of 3 to 5).
In an embodiment of step , the composition comprises 1 to 80mg of a concentrated extract of Haematococcus containing not less than 2.0% astaxanthin, 0.5 to 5mg of a piperine titer 95% of a dry extract obtained from the fruit of Piper nigrum, 40 to 800mg of an extract of the gum resin of Lacca dentata having a total boswellic acid titer of 70% and β boswellic acid titer of 20%, 10 to 250mg of an extract of the stems and fruits of pineapple containing bromelain corresponding to Gelatin Digestion Units (GDU) of 8 to 480, 3.5 to 50mg of coenzyme Q10, 15 to 200mg of a dry extract of the roots of Curcuma longa having a total curcumin titer of 95%, 3 to 100mg of an extract of the flowers of Tagetes erecta having a titer of 20%, 16 to 100mg of a dry extract of blackcurrant having an Oxygen Radical Absorption Capacity (ORAC) of not less than 2 mmol/g extract of water-soluble vitamin E equivalents, 0.3 to 0.65mg of copper (from copper) and 5mg of a dry extract of Tagetes from 1 to 5mg of resveratrol (from 5% of Tagetes) of purified extracts of Tagetes, 5 to 25mg of Tinospora tinca tinctoria extract of 2mg of berca tinctoria extract, 5 to β mg of purified zinc oxide (from Tagetes).
In an embodiment of step , the composition comprises 5 to 50mg of a concentrated extract of Haematococcus containing not less than 2.0% astaxanthin, 0.75 to 4mg of a piperine titer 95% of a dry extract obtained from the fruit of Piper nigrum, 50 to 600mg of an extract of the gum resin of Lacca dentata having a total boswellic acid titer of 70% and β boswellic acid titer of 20%, 20 to 200mg of an extract of the stems and fruits of pineapple containing bromelain corresponding to 15 to 370 Gelatin Digestion Units (GDU), 3 to 25mg of coenzyme Q10, 30 to 100mg of a dry extract of the roots of Curcuma longa having a total curcumin titer of 95%, 10 to 50mg of an extract of the flowers of Tagetes erecta having a titer of 20%, 20 to 60mg of a dry extract of blackcurrant having an Oxygen Radical Absorption Capacity (ORAC) of not less than 2mmol vitamin E equivalents per gram of extract, 0.35 to 0.65mg of copper (from copper), 5 to 25mg of a dry extract of resveratrol extract from 2 to 25% of purified extracts of Tagetes (from 2 to 5mg of red sage root extract, 5 to 25mg of purified zinc oxide).
In an embodiment of step , the composition comprises 10 to 30mg of a concentrated extract of Haematococcus containing not less than 2.0% astaxanthin, 1 to 3mg of a piperine titer 95% of a dry extract obtained from the fruit of Piper nigrum, 60 to 200mg of an extract of the gum resin of Lacca dentata having a total boswellic acid titer of 70% and β boswellic acid titer of 20%, 3 to 100mg of an extract of the stems and fruits of pineapple containing bromelain corresponding to 50 to 200 Gelatin Digestion Units (GDU), 4 to 12mg of coenzyme Q10, 30 to 70mg of a total curcumin titer 95% of a dry extract of the roots of Curcuma longa, 15 to 35mg of an extract of the flowers of Tagetes erecta having a lutein titer of 20%, 20 to 40mg of a dry extract of blackcurrant having an oxygen radical uptake capacity (ORAC) of not less than 2 mmol/g of water-soluble vitamin E equivalent, 0.4 to 0.6mg of copper (from copper), 10 to 20mg of an extract of purified extract of the roots of resveratrol from 5 to 5mg of the extracts of the stems of the roots of the purified extracts of Tagetes, 5 to 5mg of the extracts of the roots of the extracts of the flowers of the resveratrol (Callitanthrin from 5mg of the purified extracts of the caraway of the trees of the yellow rice tree).
In an in vivo experimental model, it was demonstrated that the composition according to the invention was unexpectedly effective in inhibiting the expression of TNF α and promoting the recovery of retinal function.
This activity is obtained in particular by the composition of the invention. When tested alone, the different components did not provide the effect obtained with the composition, confirming a clear synergy between the tested components.
The composition according to the invention comprises natural extracts and provides a valuable supplement in the treatment of retinal diseases.
The invention further relates to oral formulations combining the compositions according to the invention described in claims 1 to 6 with Pharmaceutical excipients known in the art, which allow the formulation of the compositions of the invention into powders, tablets, pills, capsules, liquids, gels, syrups, semi-liquid mixtures, suspensions and the like, for oral ingestion by an individual, Pharmaceutical formulations for oral use can optionally be obtained by grinding the resulting mixture and, if desired, post-treating the mixture of granules with the addition of suitable adjuvants to obtain tablets or cores of pills, as solid excipients, in particular suitable excipients are fillers, such as sugars, including lactose or sucrose, cellulose formulations, such as corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidone (PVP), and various flavouring agents known in the art, such as cocoa, if desired, disintegrating agents, such as cross-linked polyvinylpyrrolidone, agar or alginic acid or a salt thereof, such as sodium alginate, said formulations can be provided in the form of chewable tablets or in liquid, soft, or soft gelatine capsules, in the form of Pharmaceutical compositions known in the art, see, Pharmaceutical excipients, e.g. gelatine, gelatin capsules .
An adjunctive method of treatment of retinal disease is also described, comprising administering to a person in need thereof a composition according to the invention as described in claims 1 to 6. The composition is administered at a dose of 50 mg/day to 5 g/day, preferably 100 mg/day to 2.5 g/day, or 200 mg/day to 1.5 g/day, more preferably 300 mg/day to 800 mg/day.