Neuroprotective effect of solubilized UDCA in focal ischemic model
First Claim
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1. A method of reducing infarction volume of an ischemic stroke in a subject having an ischemic stroke, said method comprising:
- administering to the subject a composition comprising;
(a) a bile acid material selected from the group consisting of an ursodeoxycholic acid, an aqueous soluble halo- and/or amino-derivative of an ursodeoxycholic acid, and an ursodeoxycholic acid salt;
(b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product having at least one reducing end or at least one non-reducing end and an aqueous soluble non-starch polysaccharide; and
(c) water,wherein (1) the bile acid material and the carbohydrate both remain in solution for all pH values of the solution between about pH 1 and about pH 14, (2) the bile acid material is at a dosage so that the subject receives from about 25 mg/kg to about 100 mg/kg, (3) the administering comprises administering by a route selected from the group consisting of orally administering, sublingually administering, parenterally administering, intradermally injecting, subcutaneously injecting, intrathyroidally injecting, intravenously injecting, intranasally administering, transdermally administering, and transconjunctivally administering, and (4) infarction volume is reduced.
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Abstract
The present disclosure provides compositions and methods for treating, ameliorating, or relieving at least one symptom associated with loss of blood flow to the brain including, without limitation, ischemic stroke. Compositions of the disclosure may comprise a bile acid compound and a carbohydrate, wherein both materials remain in solution for all pH values of the solution within a selected range of pH values. Symptoms may include infarct volume, functional recovery, apoptosis, and/or eNOS expression.
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14 Claims
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1. A method of reducing infarction volume of an ischemic stroke in a subject having an ischemic stroke, said method comprising:
- administering to the subject a composition comprising;
(a) a bile acid material selected from the group consisting of an ursodeoxycholic acid, an aqueous soluble halo- and/or amino-derivative of an ursodeoxycholic acid, and an ursodeoxycholic acid salt; (b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product having at least one reducing end or at least one non-reducing end and an aqueous soluble non-starch polysaccharide; and (c) water, wherein (1) the bile acid material and the carbohydrate both remain in solution for all pH values of the solution between about pH 1 and about pH 14, (2) the bile acid material is at a dosage so that the subject receives from about 25 mg/kg to about 100 mg/kg, (3) the administering comprises administering by a route selected from the group consisting of orally administering, sublingually administering, parenterally administering, intradermally injecting, subcutaneously injecting, intrathyroidally injecting, intravenously injecting, intranasally administering, transdermally administering, and transconjunctivally administering, and (4) infarction volume is reduced. - View Dependent Claims (7, 8, 9, 10, 11, 12, 13, 14)
- administering to the subject a composition comprising;
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2. A method of enhancing functional recovery in a subject having an ischemic stroke, said method comprising:
- administering to the subject a composition comprising;
(a) a bile acid material selected from the group consisting of an ursodeoxycholic acid, an aqueous soluble halo- and/or amino-derivative of an ursodeoxycholic acid, and an ursodeoxycholic acid salt; (b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product having at least one reducing end or at least one non-reducing end and an aqueous soluble non-starch polysaccharide; and (c) water, wherein (1) the bile acid material and the carbohydrate both remain in solution for all pH values of the solution between about pH 1 and about pH 14, (2) the bile acid material is at a dosage so that the subject receives from about 25 mg/kg to about 100 mg/kg, (3) the administering comprises administering by a route selected from the group consisting of orally administering, sublingually administering, parenterally administering, intradermally injecting, subcutaneously injecting, intrathyroidally injecting, intravenously injecting, intranasally administering, transdermally administering, and transconjunctivally administering, and (4) functional recovery is improved.
- administering to the subject a composition comprising;
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3. A method of increasing the expression of eNOS in a subject having an ischemic stroke, said method comprising:
- administering to the ischemic stroke subject a composition comprising;
(a) a bile acid material selected from the group consisting of an ursodeoxycholic acid, an aqueous soluble halo- and/or amino-derivative of an ursodeoxycholic acid, and an ursodeoxycholic acid salt; (b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product having at least one reducing end or at least one non-reducing end and an aqueous soluble non-starch polysaccharide; and (c) water, wherein (1) the bile acid material and the carbohydrate both remain in solution for all pH values of the solution between about pH 1 and about pH 14, (2) the bile acid material is at a dosage so that the subject receives from about 25 mg/kg to about 100 mg/kg, (3) the administering comprises administering by a route selected from the group consisting of orally administering, sublingually administering, parenterally administering, intradermally injecting, subcutaneously injecting, intrathyroidally injecting, intravenously injecting, intranasally administering, transdermally administering, and transconjunctivally administering, and (4) eNOS expression is increased.
- administering to the ischemic stroke subject a composition comprising;
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4. A method of inhibiting apoptosis and increasing the expression of eNOS in a subject having an ischemic stroke, said method comprising:
- administering to the ischemic stroke subject a composition comprising;
(a) a bile acid material selected from the group consisting of an ursodeoxycholic acid, an aqueous soluble halo- and/or amino-derivative of an ursodeoxycholic acid, and an ursodeoxycholic acid salt; (b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product having at least one reducing end or at least one non-reducing end and an aqueous soluble non-starch polysaccharide; and (c) water, wherein (1) the bile acid material and the carbohydrate both remain in solution for all pH values of the solution between about pH 1 and about pH 14, (2) the bile acid material is at a dosage so that the subject receives from about 25 mg/kg to about 100 mg/kg, (3) the administering comprises administering by a route selected from the group consisting of orally administering, sublingually administering, parenterally administering, intradermally injecting, subcutaneously injecting, intrathyroidally injecting, intravenously injecting, intranasally administering, transdermally administering, and transconjunctivally administering, and (4) apoptosis is reduced and eNOS expression is increased.
- administering to the ischemic stroke subject a composition comprising;
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5. A method of treating at least one symptom of ischemic stroke in a subject having an ischemic stroke, said method comprising:
- administering to the subject a composition comprising;
(a) a bile acid material selected from the group consisting of an ursodeoxycholic acid, an aqueous soluble halo- and/or amino-derivative of an ursodeoxycholic acid, and an ursodeoxycholic acid salt; (b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product having at least one reducing end or at least one non-reducing end and an aqueous soluble non-starch polysaccharide; and (c) water, wherein (1) the bile acid material and the carbohydrate both remain in solution for all pH values of the solution between about pH 1 and about pH 14, (2) the bile acid material is at a dosage so that the subject receives from about 25 mg/kg to about 100 mg/kg, (3) the administering comprises administering by a route selected from the group consisting of orally administering, sublingually administering, parenterally administering, intradermally injecting, subcutaneously injecting, intrathyroidally injecting, intravenously injecting, intranasally administering, transdermally administering, and transconjunctivally administering, and (4) at least one symptom of ischemic stroke is treated.
- administering to the subject a composition comprising;
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6. A method of delivering a bile acid material to the brain in a subject having an ischemic stroke comprising:
- administering to the subject a composition comprising;
(a) a bile acid material selected from the group consisting of an ursodeoxycholic acid, an aqueous soluble halo- and/or amino-derivative of an ursodeoxycholic acid, and an ursodeoxycholic acid salt; (b) a carbohydrate selected from the group consisting of an aqueous soluble starch conversion product having at least one reducing end or at least one non-reducing end and an aqueous soluble non-starch polysaccharide; and (c) water, wherein (1) the bile acid material and the carbohydrate both remain in solution for all pH values of the solution between about pH 1 and about pH 14, (2) the bile acid material is at a dosage so that the subject receives from about 25 mg/kg to about 100 mg/kg, (3) the administering comprises administering by a route selected from the group consisting of orally administering, sublingually administering, parenterally administering, intradermally injecting, subcutaneously injecting, intrathyroidally injecting, intravenously injecting, intranasally administering, transdermally administering, and transconjunctivally administering, and (4) a bile acid material is delivered to the brain.
- administering to the subject a composition comprising;
Specification