Summary of the invention
Purpose of the present invention mainly provide a kind of under room temperature and cryogenic conditions, have good solubility can be water-soluble the preparation technology of Gallate propyl ester lyophilized injectable powder.
Preparation technology of the present invention is: the raw material water dissolution that principal agent Gallate propyl ester and pharmaceutic adjuvant are formed, stir and add pharmaceutically useful freeze drying excipient or do not add freeze drying excipient, remove thermal source, aseptic filtration, dosage according to medicine carries out packing, and remains solution and enter temperature before the freeze drying box at 40～80 ℃, puts into the freeze drying box that cools the temperature to below-20～-50 ℃ lyophilization of reducing pressure, the product gland of being frozen into is sealed up, and gets finished product.
Remarkable advantage of the present invention is: than prior art, this preparation technology utilizes the Gallate propyl ester to be dissolved in hot water and slightly is dissolved in the character of normal-temperature water solution, adopt the method for insulation to prevent that the Gallate propyl ester from separating out crystallization before lyophilizing, adopt the method for quick-freezing simultaneously, can prevent effectively that than the method for routine cooling the Gallate propyl ester from separating out crystallization and keeping the direct lyophilizing molding of solution before lyophilizing, after decompression adds heat extraction moisture, be the good loose powder shape of dissolubility; This preparation technology gained can be water-soluble Gallate propyl ester lyophilized injectable powder have under room temperature and cryogenic conditions thereof soluble in water and help preparing the remarkable advantage of injection, during use, adding sodium-chloride water solution or D/W can dissolve fast in this Gallate propyl ester freeze-dried composition.The freeze-dried composition of this prepared not only solubility property is good, easy to use, and its manufacturing process is simple, and production cost is low.
The specific embodiment
The raw material water dissolution that principal agent Gallate propyl ester and pharmaceutic adjuvant are formed, stir and add pharmaceutically useful freeze drying excipient or do not add freeze drying excipient, remove thermal source, aseptic filtration, dosage according to medicine carries out packing, and remains solution and enter temperature before the freeze drying box at 40～80 ℃, puts into the freeze drying box that cools the temperature to below-20～-50 ℃ lyophilization of reducing pressure, the product gland of being frozen into is sealed up, and gets finished product.
Wherein, decompression lyophilization step is: (1) pre-freeze: with goods pre-freeze 4 hours, temperature was reduced to below-40 ℃; (2) distillation: improve shelf temperature to 3 ℃, pressure is controlled at 10～25pa, distillation goods 9 hours; (3) drying: improve shelf temperature to 40 ℃, pressure is controlled at 5～15pa, dried product 7 hours.
The raw material that principal agent Gallate propyl ester and pharmaceutic adjuvant are formed and the weight ratio proportioning of freeze drying excipient are 1: 5～5: 1.
Freeze drying excipient is one or more the mixture in cyclodextrin, beta-schardinger dextrin-, mannitol, sorbitol, sodium chloride, glucose, fructose, sucrose, lactose, the xylitol.
The finished product that makes has following feature: outward appearance presents the loose powder shape, and a bottle wall does not have the needle-like crystallization and separates out, and very easily is dissolved at normal temperatures in the conventional medical solvent such as water for injection, puts no crystallization for a long time and separates out.
Embodiment 1
Get Gallate propyl ester 60mg and an amount of medical accessory, add 2ml water, being stirred to the Gallate propyl ester is dissolved in the water fully, solution after the stirring and dissolving filters with the sintered filter funnel of crossing through sterilization treatment in advance, and filtrate is sub-packed in the aseptic cillin bottle of 2ml, adopts the method for insulation to remain in the cillin bottle solution temperature at 60 ℃, and open freeze drying box in advance, temperature is reduced in advance-40 ℃, send into the cillin bottle that has been incubated, quick-freezing decompression lyophilization.
The lyophilization step that wherein reduces pressure is (1) sample pre-freeze: products temperature is reduced to below-40 ℃; (2) sample distillation: improve shelf temperature to 3 ℃, pressure is controlled at 10～25pa, distils 9 hours; (3) sample drying: improve shelf temperature to 40 ℃, pressure is controlled at 5～15pa, dry 7 hours.
Embodiment 2
Get Gallate propyl ester 60mg and an amount of medical accessory, add 2ml water, be stirred to the Gallate propyl ester and be dissolved in the water fully, under stirring condition, add 5～200mg mannitol; Solution after the stirring and dissolving filters with the sintered filter funnel of crossing through sterilization treatment in advance, filtrate is sub-packed in the aseptic cillin bottle of 2ml, adopt the method for insulation to remain in the cillin bottle solution temperature at 40 ℃, and open freeze drying box in advance, temperature is reduced in advance-50 ℃, send into the cillin bottle that has been incubated, the rapid decompression lyophilization, seal, promptly get can be water-soluble Gallate propyl ester freeze-dried composition.
The lyophilization step that wherein reduces pressure is (1) sample pre-freeze: products temperature is reduced to below-40 ℃; (2) sample distillation: improve shelf temperature to 3 ℃, pressure is controlled at 10～25pa, distils 9 hours; (3) sample drying: improve shelf temperature to 40 ℃, pressure is controlled at 5～15pa, dry 7 hours.
Embodiment 3
Get Gallate propyl ester 60mg and an amount of medical accessory, add 2ml water, be stirred to the Gallate propyl ester and be dissolved in the water fully, under stirring condition, add the pharmaceutically useful freeze drying excipient sorbitol of 5～200mg; Solution after the stirring and dissolving filters with the sintered filter funnel of crossing through sterilization treatment in advance, filtrate is sub-packed in the aseptic cillin bottle of 2ml 90, adopt the method for insulation to remain in the cillin bottle solution temperature at 80 ℃, and open freeze drying box in advance, temperature is reduced in advance-20 ℃, send into the cillin bottle that has been incubated, the rapid decompression lyophilization, seal, promptly get can be water-soluble Gallate propyl ester freeze-dried composition.
The lyophilization step that wherein reduces pressure is (1) sample pre-freeze: products temperature is reduced to below-40 ℃; (2) sample distillation: improve shelf temperature to 3 ℃, pressure is controlled at 10～25pa, distils 9 hours; (3) sample drying: improve shelf temperature to 40 ℃, pressure is controlled at 5～15pa, dry 7 hours.
The present invention can be water-soluble Gallate propyl ester freeze-dried composition owing to have fine solubility and stability, not only guaranteed clinical application safety, the also corresponding layoutprocedure of simplifying the medical personnel reduces working strength, has popularizing application prospect preferably.