Treatment of central nervous system disorders by intranasal administration of immunoglobulin g
a central nervous system and immunoglobulin technology, applied in the direction of antibody medical ingredients, drug compositions, peptides, etc., can solve the problem of limited resource of igg, and achieve the effect of reducing the necessary igg dose, increasing the therapeutic potential, and improving treatment efficiency
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[0291]In a first aspect, the disclosure provides a method for treating a central nervous system (CNS) disorder in a subject in need thereof, the method comprising: delivering a therapeutically effective amount of a composition comprising pooled human immunoglobulin G (IgG) to the brain of the subject, wherein delivering the composition to the brain comprises intranasally administering the composition directly to a nasal epithelium of the subject.
[0292]In one embodiment of the first aspect, at least 40% of the pooled human IgG administered to the subject contacts the nasal epithelium of the subject.
[0293]In one embodiment of the first aspect, at least 50% of the pooled human IgG administered to the subject contacts the nasal epithelium of the subject.
[0294]In one embodiment of the first aspect, at least 60% of the pooled human IgG administered to the subject contacts the nasal epithelium of the subject.
[0295]In one embodiment of the first aspect, the nasal epithelium is the olfactory...
example 1
ity of Intranasal Administration of IgG in Rats
[0345]A study was conducted to examine the tolerability of intranasal administration of IgG in rats. The purpose of this study was to determine the tolerability of rats to intranasal IgG administration at various concentrations and preparations.
[0346]Experimental Design:
[0347]IgG was prepared as a liquid protein solution or as a microsphere preparation. The liquid IgG protein solution was prepared in glycine at 200 mg / mL and 100 mg / mL and had a pH of 5.1-5.3. The IgG microsphere preparation was prepared at 200 mg / mL and 150 mg / mL in PEG. The IgG preparations were administered to 8 anesthetized, adult male Sprague Dawley rats.
[0348]Prior to anesthesia, each rat was weighed. An anesthesia cocktail was prepared and full, half, and quarter anesthesia doses were calculated according to the animal's weight with a full dose containing 30 mg / kg ketamine, 6 mg / kg xylazine, and 1 mg / kg acepromazine. The anesthesia was administered subcutaneously ...
example 2
n of Liquid, Microsphere, and Fragment Biodistribution at 30 and 90 Minutes
[0355]The purpose of this study was to quantify the amount of intranasally administered IgG that reaches the central nervous system and peripheral tissues in anesthetized rats. Specifically, the biodistribution of different formulations and modes of administration were compared. The different formulations and modes of administration are described in Table 4.
TABLE 4Formulations and modes of administration used inbiodistribution study.125I radiolabeled IgGFormulationMode of AdministrationLiquid proteinIntranasal (biodistribution measured at 30 minformulationpost administration)Liquid proteinIntravenous biodistribution measured at 30 minformulationpost administration)Liquid proteinIntranasal (biodistribution measured at 90 minformulationpost administration)Microsphere formulationIntranasal (biodistribution measured at 30 minpost administration)Microsphere formulationIntranasal (biodistribution measured at 90 min...
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