Extract and formulation including extract
Inventors
Nakazawa, Yoshitaka • Shibayama, Yoji • Nakamura, Ko
Assignees
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Publication Number
US-11529374-B2
Publication Date
2022-12-20
Expiration Date
Abstract
It is an object of the present invention to provide an extract from inflamed skins of rabbits inoculated with vaccinia virus wherein the quality is more stabilized, and a preparation containing the extract, etc. The use of the amount of N-acetylneuraminic acid contained in an extract from inflamed skins of rabbits inoculated with vaccinia virus and a preparation containing the extract as an index makes possible to warrant the quality of each manufacturing lot of the extract and the preparation in more stable manner. The extract from inflamed skins of rabbits inoculated with vaccinia virus and the preparation containing the extract which are manufactured as above, and in which the quality thereof becomes more stable, are warranted to maintain efficacy and safety in more strict manner, and thus extremely useful.
Core Innovation
The invention relates to stabilizing quality of a preparation containing an extract from inflamed skins of rabbits inoculated with vaccinia virus by reducing variations in the content of N-acetylneuraminic acid among manufacturing lots. For each manufacturing lot, the amount of N-acetylneuraminic acid contained in the preparation is measured, and the content is confirmed to be 4000 ng or more per unit of the extract in the preparation. The invention uses N-acetylneuraminic acid as a lot-to-lot quality index.
The preparation and extract are derived from a manufacturing method that includes collecting inflamed skin tissues of rabbits inoculated with vaccinia virus, crushing the inflamed tissues, and conducting an extraction treatment using an extraction solvent selected from water, phenol water, physiological saline, or phenol-added glycerin water. The extracted mixture is allowed to stand and is heated, and crude extract is obtained by filtrating or centrifuging to give a filtrate or supernatant with tissue fragments removed.
A deproteinizing treatment is performed by adjusting pH to acidic pH, heating, and filtering or centrifuging, followed by adjusting to basic pH, heating, and separating again to obtain a deproteinized filtrate or supernatant. Further purification and extract recovery are achieved by adjusting the deproteinized filtrate or supernatant to pH 3.5 to 5.5 and adsorbing with an adsorbent, followed by preparing an adsorption mixture with an extraction solvent and adjusting the mixture to pH 9 to 12 for elution. The eluted component yields the extract, which is then incorporated into an injectable preparation or a tablet preparation.
Claims Coverage
The partial content provides four independent claims. The inventive core is the reduction of lot-to-lot variation in N-acetylneuraminic acid content through measurement per manufacturing lot and qualification against a defined threshold, in combination with a specified manufacturing method to obtain the extract.
Lot-to-lot reduction by measured N-acetylneuraminic acid with minimum acceptance
Variations in the content of N-acetylneuraminic acid among manufacturing lots are reduced by measuring the amount of N-acetylneuraminic acid contained in the preparation for each manufacturing lot and confirming the content is 4000 ng or more per unit of the extract in the preparation.
Preparation from vaccinia-inoculated rabbit inflamed skin extract via multi-step manufacturing
The extract is obtained by a manufacturing method comprising collecting inflamed skin tissues of rabbits subjected to intradermal inoculation with vaccinia virus, crushing and conducting an extraction treatment to give a crude extract; adjusting to acidic pH for a deproteinizing treatment and then adjusting to basic pH; adjusting the filtrate or supernatant to pH 3.5 to 5.5 and adsorbing with an adsorbent; and adding an extraction solvent, adjusting to pH 9 to 12, and eluting the adsorbed component to give the extract.
Method for making injectable or tablet preparations with quantified standardization
Providing an extract from inflamed skins of rabbits inoculated with vaccinia virus having a predetermined amount of N-acetylneuraminic acid where variations among manufacturing lots are reduced, with the amount being 4000 ng or more per unit of the extract, and incorporating the extract into an injectable preparation or a tablet preparation.
Analgesic effect by administering lot-qualified N-acetylneuraminic-acid standardized preparation
Providing an analgesic effect by administering a preparation containing an extract from inflamed skins of rabbits inoculated with vaccinia virus in which variations in N-acetylneuraminic acid among manufacturing lots are reduced by measuring for each manufacturing lot and confirming content of 4000 ng or more per unit of the extract in the preparation.
The claims focus on reducing lot-to-lot variation in N-acetylneuraminic acid by measuring per manufacturing lot and qualifying preparations that meet a minimum content of 4000 ng or more per unit of the extract. This is paired with a defined manufacturing workflow for producing the extract from inflamed vaccinia-inoculated rabbit skins, including extraction, deproteinizing treatment, adsorption at pH 3.5 to 5.5, and elution at pH 9 to 12. Independent claim coverage also extends to making injectable or tablet preparations and administering the preparation to provide an analgesic effect.
Stated Advantages
Reduces manufacturing variability among manufacturing lots.
Provides assurance of efficacy/safety as stated in the provided patent text.
Improves lot-to-lot quality stabilization by using N-acetylneuraminic acid as a lot-to-lot quality index.
Documented Applications
Providing an analgesic effect by administering a preparation containing an extract from inflamed skins of rabbits inoculated with vaccinia virus.
Manufacturing and incorporating the extract into an injectable preparation.
Manufacturing and incorporating the extract into a tablet preparation.
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