Patent Application
20250177426
This disclosure relates to compositions for treatment of cognitive disorders such as Alzheimer's disease.
Alzheimer's disease is a common form of dementia. Although it may begin earlier in some cases, symptoms of Alzheimer's disease generally begin in individuals 65 years and older. The disease is characterized by a slow and gradual cognitive decline that manifests early as simple memory loss. Later, the individual gradually loses cognitive function to the point that they are entirely dependent on caregivers. In late-stage Alzheimer's, the individual often loses their ability to speak.
Despite widespread and omnipresent suffering from Alzheimer's disease, there is no cure. Indeed, there are only a handful of therapies to treat Alzheimer's disease, and they only offer marginal relief. And this is all while the cost of Alzheimer's disease in money, time, and anguish takes an increasing toll on the world population as life expectancy increases.
Although the cause of Alzheimer's disease is not completely understood, there is increasing evidence that Aβ protein (abeta) and tau protein play a significant role. For instance, Alzheimer's disease is characterized by the deposition of Aβ amyloid fibrils, which are extracellular deposits of Aβ protein plaques in the gray matter of the brain. Alzheimer's disease is further characterized by the deposition of neurofibrillary tangles, which are abnormal accumulations of tau protein inside neurons.
Methods and compositions for treatment of dementia are provided. An exemplary embodiment is a method for treatment of the patient. The method comprises administering an
effective dose of a compound having the formula wherein R1 includes
where n is an integer selected from 0 to 5, R2, R3, and R4 are independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, Ar, hAr, where Ar includes phenyl independently substituted with 0-5 substituents where each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, hAr, where hAr includes a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with (Alk, OAlk, NHAlk, N(Alk)2, or a halogen). R1 may further include
where X comprises O, NR, or bond, wherein R2 and R3 independently comprise H, C1-6 Alk, C3-6 cycloalkyl, or cyclized to form ring (each containing or substituted with 0-3 heteroatoms), Ar, or hAr, wherein R4 is selected from the group consisting of C1-6 Alk, C3-6 cycloalkyl (each containing or substituted with 0-3 heteroatoms, NHAlk, N(Alk)2, Ar, or hAr, wherein Ar comprises phenyl independently substituted with 0-5 substituents wherein each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, hAr, wherein hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, or hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. R1 may further include
where A1, A2, A3, and A4 are independently selected from the group consisting of N or CR2, where R2 is selected from the group consisting of H, C1-6 Alk, C3-6 cycloalkyl, Ar, or hAr, where Ar comprises phenyl independently substituted with 0-5 substituents where each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, hAr, where hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. R1 may further include
where A1, A2, and A3 are independently selected from the group consisting of N, O, S, or CR2, where R2 is selected from the group consisting of H, C1-6 Alk, C3-6 cycloalkyl, Ar, or hAr, wherein Ar comprises phenyl independently substituted with 0-5 substituents wherein each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, or hAr, where hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. R1 may further include
where R2 is selected from the group consisting of H, C1-6 Alk, C3-6 cycloalkyl comprising or substituted with 0-3 heteroatoms, Ar, or hAr, wherein Ar comprises phenyl independently substituted with 0-5 substituents where each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, hAr(alkyl, O-alkyl, NH-alkyl, N(alkyl)2, wherein hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. R1 may further include
where X is selected from the group consisting of C2-6 Alk, C3-6 cycloalkyl each containing or substituted with 0-3 heteroatoms, Ar, hAr, or formula I with structure
where Ar includes phenyl independently substituted with 0-5 substituents wherein each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, hAr(alkyl, O-alkyl, NH-alkyl, N(alkyl)2, where hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. The term Alk may refer to an alkyl group. The effective dose may have a concentration of between about 10 μM and about 150 μM. The effective dose may have a concentration of between about 50 μM and about 100 μM. The effective dose may have a concentration of between about 100 μM and about 150 μM. The effective dose may have a concentration of between about 20 μM and about 40 μM. The effective dose may have a concentration of between about 40 μM and about 60 μM. The effective dose may have a concentration of between about 60 μM and about 80 μM. The effective dose may have a concentration of between about 80 μM and about 100 μM. The effective dose may have a concentration of between about 100 μM and about 120 μM. The effective dose may have a concentration of between about 100 μM and about 140 μM.
Another general aspect is a method for treatment of a patient. The method includes administering an effective dose of a compound having the formula
where R1 is selected from the group consisting of
where R2-R5 are independently selected from the group consisting of H, C1-6 Alk, C3-6 cycloalkyl, Ar, hAr. In the alternative, R1 may include
where R2-5 are independently selected from the group consisting of H, C1-6Alk, C3-6 cycloalkyl, Ar, hAr, or group selected from
where R2-5 are independently selected from the group consisting of H, C1-6 Alk, C3-6 cycloalk, Ar, hAr, I, II, III, or IV. R6-8 may be independently selected from the group consisting of H, C1-6 Alk, C3-6 cycloalk, Ar, or hAr, wherein Ar comprises phenyl independently substituted with 0-5 substituents wherein each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, hAr, wherein hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. The effective dose may have a concentration of between about 20 μM and about 40 μM. The effective dose may have a concentration of between about 40 μM and about 60 μM. The effective dose may have a concentration of between about 60 μM and about 80 μM. The effective dose may have a concentration of between about 80 μM and about 100 μM. The effective dose may have a concentration of between about 100 μM and about 120 μM. The effective dose may have a concentration of between about 100 μM and about 140 μM.
An exemplary embodiment is a method for treatment of the patient. The method comprises administering an effective dose of a compound having the formula
where R1 includes the group
where R2 and R3 are independently selected from the group consisting of: H, C1-C6 alkyl, C3-C6 cycloalkyl, or cyclized to form a ring wherein each ring contains or is substituted with 0-3 heteroatoms, Ar, hAr, wherein Ar comprises phenyl independently substituted with 0-5 substituents wherein each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, or hAr, wherein hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. R1 may further include the group
where R2 is independently selected from the group consisting of: H, C1-C6 alkyl, C3-C6 cycloalkyl, or cyclized to form a ring wherein each ring contains or is substituted with 0-3 heteroatoms, Ar, hAr, where Ar comprises phenyl independently substituted with 0-5 substituents wherein each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, or hAr, wherein hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. R1 may further include the group
where n is an integer selected from 0 to 5, wherein R2, R3, and R4 are independently selected from the group consisting of: H, C1-C6 alkyl, C3-C6 cycloalkyl, or cyclized to form a ring wherein each ring contains or is substituted with 0-3 heteroatoms, Ar, hAr, where Ar comprises phenyl independently substituted with 0-5 substituents wherein each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, or hAr, wherein hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, or hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. R1 may further include the group
where X is selected from the group consisting of O, NR, or a bond, R2 and R3 are independently selected from the group consisting of: H, C1-C6 alkyl, C3-C6 cycloalkyl, or cyclized to form a ring where each ring contains or is substituted with 0-3 heteroatoms, Ar, hAr, wherein Ar comprises phenyl independently substituted with 0-5 substituents wherein each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, hAr, where hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. The effective dose may have a concentration of between about 20 μM and about 40 μM. The effective dose may have a concentration of between about 40 μM and about 60 μM. The effective dose may have a concentration of between about 60 μM and about 80 μM. The effective dose may have a concentration of between about 80 μM and about 100 μM. The effective dose may have a concentration of between about 100 μM and about 120 μM. The effective dose may have a concentration of between about 100 μM and about 140 μM.
Another general aspect is a method for treatment of a patient. The method includes administering an effective dose of a compound having the formula
where R1 includes the group
where n is an integer selected from 0 to 5, wherein R2, R3, and R4 are independently selected from the group consisting of: H, C1-C6 alkyl, C3-C6 cycloalkyl, or cyclized to form a ring where each ring contains or is substituted with 0-3 heteroatoms, Ar, or hAr, where Ar comprises phenyl independently substituted with 0-5 substituents wherein each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, or hAr, where hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. R1 may further include the group
where R2 and R3 are independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, Ar, hAr, Na+, or K+. R1 may further include the group
wherein R2 and R3 are independently selected from the group consisting of: H, C1-C6 alkyl, C3-C6 cycloalkyl, or cyclized to form a ring wherein each ring contains or is substituted with 0-3 heteroatoms, Ar, or hAr, where Ar comprises phenyl independently substituted with 0-5 substituents wherein each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, hAr, wherein hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, or hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. The effective dose may have a concentration of between about 40 μM and about 60 μM. The effective dose may have a concentration of between about 60 μM and about 80 μM. The effective dose may have a concentration of between about 80 μM and about 100 μM. The effective dose may have a concentration of between about 100 μM and about 120 μM. The effective dose may have a concentration of between about 100 μM and about 140 μM.
An exemplary embodiment is a method for treatment of a patient. The method includes administering an effective dose of a compound having the formula
where R1 is selected from the group consisting of:
where R2-5 are independently selected from the group consisting of H, C1-6 Alk, C3-6 cycloalk, Ar, or hAr. Alternatively, R1 may comprise
where R2-5 are independently selected from the group consisting of H, C1-6Alk, C3-6 cycloalk, Ar, hAr, or a group selected from: I.
where R6-8 are independently selected from the group consisting of H, C1-6 Alk, C3-6 cycloalk, Ar, or hAr, wherein Ar comprises phenyl independently substituted with 0-5 substituents where each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, or hAr, where hAr comprises a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with Alk, OAlk, NHAlk, N(Alk)2, or a halogen. The effective dose may have a concentration of between about 40 μM and about 60 μM. The effective dose may have a concentration of between about 60 μM and about 80 μM. The effective dose may have a concentration of between about 80 μM and about 100 μM. The effective dose may have a concentration of between about 100 μM and about 120 μM. The effective dose may have a concentration of between about 100 μM and about 140 μM.
The disclosed subject matter relates to a pharmaceutical composition containing the natural compound sinapic acid O-glucoside that can be effectively used as a pharmaceutical composition or health functional food to prevent, treat, or improve neurodegeneration or neuroinflammatory diseases. The pharmaceutical composition for preventing or treating neurodegeneration or neuroinflammatory diseases comprises: (A) sinapic acid O-glucoside as an active ingredient (B) ProDrug version of the active ingredient (C) any composition of sinapic acid O-glucoside as an active primary ingredient (D) sinapic acid O-glucoside analog or pharmacol, acceptable salt, solvate, ester, amide, clathrate, stereoisomer, enantiomer, prodrug or analog thereof, or a combination thereof.
Several studies have suggested that reducing Aβ aggregation, or promoting its clearance from the brain, could potentially improve neuronal survival and alleviate some symptoms of Alzheimer's disease. For instance, many experimental Alzheimer's disease treatments aim to reduce Aβ levels in the brain, either by preventing Aβ production, inhibiting its aggregation, or promoting its clearance.
However, it's important to note that while reducing Aβ fibril formation could theoretically help improve neuronal survival, this is only one aspect of a complex disease process. Other factors, such as tau protein aggregation, inflammation, oxidative stress, and vascular factors, also play a role in the development and progression of Alzheimer's disease. A disclosed treatment includes treating a patient with an effective dose of the disclosed compositions. The term effective dose, as used herein, may include a dose capable of improving a factor indicative of neural survival, neural inflammation, cellular toxicity, Aβ fibril formation, tau protein aggregation, inflammation, oxidative stress, and vascular factors. Examples of factors that may be improved by an effective dose from one or more of the disclosed compositions are disclosed in results/data in
The disclosed subject matter includes novel prodrugs with reduced polarity that offer significant improvements compared to the parent compounds, including: (1) Improved passive permeability. This feature facilitates their efficient diffusion through various physiological membranes, including the intestines, target organ cell membranes, and the blood-brain barrier. (2) Increased bioavailability. Higher passive permeability allows the prodrugs achieve greater bioavailability, allowing for higher concentrations to be delivered to the intended site(s) of action. (3) Improved brain penetration. In a similar fashion, increased passive permeability will allow for greater passage through the blood-brain barrier, potentially enabling enhanced drug delivery to the central nervous system for therapeutic applications. (4) Select examples of the disclosed prodrugs are likely substrates for endogenous transporters expressed in diverse cell types throughout the body. This characteristic augments their permeability across various physiological barriers, expanding their therapeutic potential.
Referring to
Examples of prodrugs for SAG may include the following structure
herein referred to as parent compound (1).
In various embodiments, R may include, but is not limited to any of the following groups:
Another example of a prodrug for SAG may include a sugar prodrug the following structure:
In various embodiments, R1 may include, but is not limited to any of the following groups:
R2-5 may be independently selected from the following: H, C1-6Alk, C3-6 cycloalk, Ar, or hAr. Alternatively, R1 may include, but is not limited to any of the following groups:
R6-8 may be independently selected from the following: H, C1-6 Alk, C3-6 cycloalk, Ar, or hAr. Ar may include phenyl independently substituted with 0-5 substituents where each substituent is independently C1-C6 alkyl, C3-C6 cycloalkyl, Ar, hAr(alkyl, O-alkyl, NH-alkyl, or N(alkyl)2. hAr may include a 5-7 membered heteroaryl ring independently substituted with 0-6 substituents comprising C1-6 Alk containing 0-3 heteroatoms, Ar, hAr substituted with (Alk, OAlk, NHAlk, N(Alk)2, or a halogen.
An example of a prodrug for neoliquiritin may comprise that following structure:
herein referred to as parent compound (2).
In various embodiments, a prodrug with the following structure
herein referred to as parent compound (3), may be administered to a patient for treatment of a cognitive disorder such as Alzheimer's disease.
In various embodiments, a prodrug with the following structure
herein referred to as parent compound (4), may be administered to a patient for treatment of a cognitive disorder such as Alzheimer's disease.
In various embodiments, a first synthetic route for parent compound (1) comprises:
where step 1 comprises reacting with malonic acid, piperzine, and toluene at 80 C; step 2 comprises reacting with sulfuric acid and alcohol at 75 C, step 3 comprises reacting with TBAB and 20% K2CO3 at 65 C; and step 4 comprises reacting with TBAF or Pd(Ph)4 or H2.
A second synthetic route for parent compound (1) comprises:
where step 1 comprises reacting with AcCl or SiR3Cl or AllocCl or BnCl in basic conditions; step 2 comprises reacting with H2 and Pd/C (X═OH); step 3 comprises reacting with POBr3 (X═Br); step 4 comprises reacting with TBAB and K2CO3 (X═OH); step 5 comprises reacting with K2CO3 and DMA (X═Br); step 6 comprises reacting with piperazine and toluene at 80 C; and step 7 comprises reacting with NaOH or TBAF or PdPh4 or H2 and Pd/C.
A third synthetic route for parent compound (1) comprises:
where step 1 comprises reacting with malonic acid, piperazine, p-aminotoluene, and toluene at 80 C; step 2 comprises reacting with sulfuric acid and alcohol at 75 C; step 3 comprises reacting with TBAB and 20% K2CO3 at 65 C; step 4 comprises reacting with NaOH, H20, and EtOH; step 5 comprises reacting with TFAA in basic conditions; step 6 comprises reacting with R1OH in basic conditions; and step 7 comprises reacting with 0.1% NaOH, H2O, and DMA.
Referring to
Sample A, which is a substance based on a traditional treatment, showed significant decrease in fibrillization at 51%. Sample A was subsequently fractionated to identify one or more compounds in Sample A. Accordingly, Sample A was fractionated into polar and nonpolar fractions. 4540 compounds were identified in the nonpolar fraction using a C18 column in the Ometa platform. The bioactivity was around 30%. 2825 compounds were identified in the polar fraction using a HILIC column in the Ometa platform. The bioactivity was around 50%. The compounds found to be responsible in the polar fraction are sinapic acid 0-glycoside and neoliquiritin.
Accordingly, the rest of the graph shown in
Referring to
The solution of 10 μM Aβ and 1 μM SAG showed a cell survival of 80%. The solution of 10 μM Aβ and 10 μM SAG showed a cell survival of 82%. The solution of 10 μM Aβ and 50 μM SAG showed a cell survival of 79%. The solution of 10 μM Aβ and 100 μM SAG showed a cell survival of 84%. And the solution of 10 μM Aβ and 150 μM SAG showed a cell survival of 85%. A trendline 405 on the bar graph 400 indicates that increasing a concentration of SAG is positively correlated with an increase in cell survival.
Referring to
Referring to
The sample comprising 1 μM SAG, 1 μM of PPF tau protein, and SH-SY5Y cells had a cell survival of 65%. The sample comprising 10 μM SAG, 1 μM of PPF tau protein, and SH-SY5Y cells had a cell survival of 88%. The sample comprising 50 μM SAG, 1 μM of PPF tau protein, and SH-SY5Y cells had a cell survival of 89%. The sample comprising 100 μM SAG, 1 μM of PPF tau protein, and SH-SY5Y cells had a cell survival of 96%. The sample comprising 150 μM SAG, 1 μM of PPF tau protein, and SH-SY5Y cells had a cell survival of 97%. A trendline 605 in the bar graph 600 indicates a positive correlation between concentration of SAG and survival of SH-SY5Y cells.
Referring to
The sample with 10 μM Aβ protein and 100 μM neoliquiritin was shown to have a 53% fibrillization as compared to the control. The sample with 10 μM Aβ protein and 100 μM Sebiricose A5 was shown to have 86% fibrillization as compared to the control. The sample with 10 μM Aβ protein and 100 μM (Z)SA glycoside was shown to have 86% fibrillization as compared to the control. The sample with 10 μM Aβ protein and 100 μM (E)SA glycoside was shown to have a 51% fibrillization as compared to the control. Accordingly neoliquiritin and (E)SA glycoside were shown to effectively reduce Aβ fibrils when compared to Sebiricose A5 and (Z)SA glycoside.
Referring to
As shown in the bar graph 800, the sample with 10 μM Aβ protein and 150 μM neoliquiritin was shown to have a 48% fibrillization of Aβ protein as compared to the control. The sample with 10 μM Aβ protein and 100 μM neoliquiritin was shown to have a 49% fibrillization of Aβ protein as compared to the control. The sample with 10 μM Aβ protein and 50 μM neoliquiritin was shown to have a 61% fibrillization of Aβ protein as compared to the control. The sample with 10 μM Aβ protein and 10 μM neoliquiritin was shown to have a 78% fibrillization of Aβ protein as compared to the control. The sample with 10 μM Aβ protein and 1 μM neoliquiritin was shown to have a 89% fibrillization of Aβ protein as compared to the control. The sample with 10 μM Aβ protein and 100 nM neoliquiritin was shown to have a 90% fibrillization of Aβ protein as compared to the control. Accordingly, it was found that neoliquiritin reduces Aβ fibrillization.
Referring to
The sample containing 150 μM neoliquiritin and 10 μM Aβ protein was found to have 48% fibrillization of Aβ protein. The sample containing 100 μM neoliquiritin and 10 μM Aβ protein was found to have 49% fibrillization of Aβ protein. The sample containing 50 μM neoliquiritin and 10 μM Aβ protein was found to have 61% fibrillization of Aβ protein. The sample containing 10 μM neoliquiritin and 10 μM Aβ protein was found to have 77% fibrillization of Aβ protein. The sample containing 1 μM neoliquiritin and 10 μM Aβ protein was found to have 89% fibrillization of Aβ protein. The sample containing 100 nM neoliquiritin and 10 μM Aβ protein was found to have 89% fibrillization of Aβ protein.
The sample containing 100 μM liquiritigenin and 10 μM Aβ protein was found to have 83% fibrillization of Aβ protein. The sample containing 50 μM liquiritigenin and 10 μM Aβ protein was found to have 97% fibrillization of Aβ protein. The sample containing 10 μM liquiritigenin and 10 μM Aβ protein was found to have 92% fibrillization of Aβ protein. The sample containing 10 μM liquiritigenin and 10 μM Aβ protein was found to have 90% fibrillization of Aβ protein. The sample containing 100 nM liquiritigenin and 10 μM Aβ protein was found to have 94% fibrillization of Aβ protein. Accordingly, the bar graph 900 shows that liquiritigenin does not effectively reduce Aβ fibrillization as well as neoliquiritin.
Referring to
Starting from the left side of the bar graph 1000, the sample containing 10 μM Aβ protein and 1 μM neoliquiritin had a 90% survival rate for the SH-SY5Y cells. The sample containing 10 μM Aβ protein and 10 μM neoliquiritin had an 89% survival rate for the SH-SY5Y cells. The sample containing 10 μM Aβ protein and 50 μM neoliquiritin had an 84% survival rate for the SH-SY5Y cells. The sample containing 10 μM Aβ protein and 100 μM neoliquiritin had an 87% survival rate for the SH-SY5Y cells. The sample containing 10 μM Aβ protein and 150 μM neoliquiritin had an 81% survival rate for the SH-SY5Y cells.
Referring to
Starting from the left most sample next to the control sample of the bar graph 1100, the sample comprising 10 μM Aβ protein and 10 μM neoliquiritin was shown to have an 86% survival for the SH-SY5Y cells. The sample comprising 10 μM Aβ protein and 1 μM neoliquiritin was shown to have an 84% survival for the SH-SY5Y cells. The sample comprising 10 μM Aβ protein and 10 μM isoliquiritigenin was shown to have an 81% survival for the SH-SY5Y cells. The sample comprising 10 μM Aβ protein and 1 μM isoliquiritigenin was shown to have an 84% survival for the SH-SY5Y cells.
The sample comprising 10 μM Aβ protein and 10 μM isoliquiritin was shown to have a 74% survival for the SH-SY5Y cells. The sample comprising 10 μM Aβ protein and 1 μM isoliquiritin was shown to have a 72% survival for the SH-SY5Y cells. The sample comprising 10 μM Aβ protein and 10 μM SAG was shown to have an 83% survival for the SH-SY5Y cells. The sample comprising 10 μM Aβ protein and 1 μM SAG was shown to have a 77% survival for the SH-SY5Y cells. The sample comprising 10 μM Aβ protein and 1 μM SAG was shown to have a 77% survival for the SH-SY5Y cells.
The sample comprising 10 μM Aβ protein and 10 μM trans-sinapic acid (T-SA) was shown to have a 77% survival for the SH-SY5Y cells. The sample comprising 10 μM Aβ protein and 1 μM T-SA was shown to have a 76% survival for the SH-SY5Y cells. The sample comprising 10 μM Aβ protein and 10 μM liquiritigenin was shown to have a 67% survival for the SH-SY5Y cells. The sample comprising 10 μM Aβ protein and 1 μM liquiritigenin was shown to have a 67% survival for the SH-SY5Y cells.
Referring to
The sample containing 10 μM Aβ protein and 100 μM sinapic acid (SA) was shown to have an 85% Aβ fibrillization as compared to the control. The sample containing 10 μM Aβ protein and 10 μM SA was shown to have a 114% Aβ fibrillization as compared to the control. The sample containing 10 μM Aβ protein and 1 μM SA was shown to have a 101% Aβ fibrillization as compared to the control. The sample containing 10 μM Aβ protein and 100 nM SA was shown to have a 105% Aβ fibrillization as compared to the control.
The sample containing 10 μM Aβ protein and 100 μM T-SA was shown to have a 79% Aβ fibrillization as compared to the control. The sample containing 10 μM Aβ protein and 10 μM T-SA was shown to have an 89% Aβ fibrillization as compared to the control. The sample containing 10 μM Aβ protein and 1 μM T-SA was shown to have a 95% Aβ fibrillization as compared to the control. The sample containing 10 μM Aβ protein and 100 nM T-SA was shown to have a 98% Aβ fibrillization as compared to the control.
The sample containing 10 μM Aβ protein and 100 μM SAG was shown to have a 46% Aβ fibrillization as compared to the control. The sample containing 10 μM Aβ protein and 10 μM SAG was shown to have a 78% Aβ fibrillization as compared to the control. The sample containing 10 μM Aβ protein and 1 μM SAG was shown to have an 85% Aβ fibrillization as compared to the control. The sample containing 10 μM Aβ protein and 100 nM SAG was shown to have a 92% Aβ fibrillization as compared to the control.
Referring to
Starting from the left side of the bar graph 1300, the sample containing 1 μM neoliquiritin and 1 μM PPF tau protein was shown to have 93% survival for SH-SY5Y cells. Moving right, the sample containing 10 μM neoliquiritin and 1 μM PPF tau protein was shown to have 94% survival for SH-SY5Y cells. The sample containing 50 μM neoliquiritin and 1 μM PPF tau protein was shown to have 88% survival for SH-SY5Y cells. The sample containing 100 μM neoliquiritin and 1 μM PPF tau protein was shown to have 86% survival for SH-SY5Y cells. The sample containing 150 μM neoliquiritin and 1 μM PPF tau protein was shown to have 78% survival for SH-SY5Y cells. The trend line 1305 in the bar graph 1300 shows that lower concentrations of neoliquiritin are more effective at increasing cell survival.
Referring to
Starting from the left side of the bar graphs 1400, relative fluorescence for Aβ fibrils at 24 hours is approximately 560000 and relative fluorescence for Aβ fibrils at 36 hours is approximately 790000. Relative fluorescence for Aβ fibrils at 46.5 hours is approximately 900000. Relative fluorescence for Aβ fibrils at 46.5 hours treatment with 50 μM SAG was shown to be approximately 640000. Relative fluorescence for Aβ fibrils at 46.5 hours treatment with 50 μM T-SA was shown to be approximately 850000. Relative fluorescence for Aβ fibrils at 46.5 hours with 50 μM neoliquiritin was shown to be approximately 660000.
Moving on to the samples that were subjected to 48 hours of treatment with Aβ protein, the sample of only Aβ protein as a starting material had a relative fluorescence of approximately 1070000. Relative fluorescence for Aβ fibrils at 48 hours with 50 μM SAG was shown to be 580000. Relative fluorescence for Aβ fibrils at 48 hours treatment with 50 μM T-SA was shown to be approximately 940000. Relative fluorescence for Aβ fibrils at 48 hours with 50 μM neoliquiritin was shown to be approximately 600000.
Moving on to the samples that were subjected to 60 hours of treatment with Aβ protein, the sample of only Aβ protein as a starting material had a relative fluorescence of approximately 1010000. Relative fluorescence for Aβ fibrils at 60 hours with 50 μM SAG was shown to be 620000. Relative fluorescence for Aβ fibrils at 60 hours with 50 μM T-SA was shown to be approximately 940000. Relative fluorescence for Aβ fibrils at 60 hours with 50 μM neoliquiritin was shown to be approximately 620000.
Moving on to the samples that were subjected to 72 hours of treatment with Aβ protein, the sample of only Aβ protein as a starting material had a relative fluorescence of approximately 980000. Relative fluorescence for Aβ fibrils at 72 hours treatment with 50 μM SAG was shown to be approximately 590000. Relative fluorescence for Aβ fibrils at 72 hours with 50 μM T-SA was shown to be approximately 770000. Relative fluorescence for Aβ fibrils at 72 hours with 50 μM neoliquiritin was shown to be approximately 640000.
In an exemplary embodiment, a dose composition containing a concentration of about 10 μM of a prodrug configured to deliver SAG may be administered to a patient suffering from cognitive disorders such as Alzheimer's disease. In various embodiments a dose composition containing a concentration of between about 10 μM and 150 μM of a prodrug configured to deliver SAG may be administered to a patient suffering from a cognitive disorder. In various embodiments a dose composition containing a concentration of between about 20 μM and 130 μM of a prodrug configured to deliver SAG may be administered to a patient suffering from a cognitive disorder. In various embodiments a dose composition containing a concentration of between about 30 μM and 110 μM of a prodrug configured to deliver SAG may be administered to a patient suffering from a cognitive disorder. In various embodiments a dose composition containing a concentration of between about 50 μM and 100 μM of a prodrug configured to deliver SAG may be administered to a patient suffering from a cognitive disorder. In various embodiments a dose composition containing a concentration of between about 60 μM and 80 μM of a prodrug configured to deliver SAG may be administered to a patient suffering from a cognitive disorder.
In an exemplary embodiment, a dose composition containing a concentration of about 10 μM of a prodrug configured to deliver neoliquiritin may be administered to a patient suffering from cognitive disorders such as Alzheimer's disease. In various embodiments a dose composition containing a concentration of between about 10 μM and 150 μM of a prodrug configured to deliver neoliquiritin may be administered to a patient suffering from a cognitive disorder. In various embodiments a dose composition containing a concentration of between about 20 μM and 130 μM of a prodrug configured to deliver neoliquiritin may be administered to a patient suffering from a cognitive disorder. In various embodiments a dose composition containing a concentration of between about 30 μM and 110 μM of a prodrug configured to deliver neoliquiritin may be administered to a patient suffering from a cognitive disorder. In various embodiments a dose composition containing a concentration of between about 50 μM and 100 μM of a prodrug configured to deliver neoliquiritin may be administered to a patient suffering from a cognitive disorder. In various embodiments a dose composition containing a concentration of between about 60 μM and 80 μM of a prodrug configured to deliver neoliquiritin may be administered to a patient suffering from a cognitive disorder.
Many variations may be made to the embodiments described herein. For instance, the amounts of the identified prodrugs and various of prodrugs, may comprise different concentrations for an effective dose and treatment. All variations are intended to be included within the scope of this disclosure, including combinations of variations. The description of the embodiments herein can be practiced in many ways. Any terminology used herein should not be construed as restricting the features or aspects of the disclosed subject matter. The scope should instead be construed in accordance with the appended claims.
This application claims the benefit of U.S. Provisional Patent Application No. 63/604,390, entitled as “METHODS AND COMPOSITIONS FOR TREATING DEMENTIA”, filed Nov. 30, 2023, which is incorporated by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63604390 | Nov 2023 | US |
