WO2014206137A1 - Packing and delivery system for freeze-dried excipient and method of preparing freeze-dried excipient - Google Patents
Packing and delivery system for freeze-dried excipient and method of preparing freeze-dried excipient Download PDFInfo
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- WO2014206137A1 WO2014206137A1 PCT/CN2014/075364 CN2014075364W WO2014206137A1 WO 2014206137 A1 WO2014206137 A1 WO 2014206137A1 CN 2014075364 W CN2014075364 W CN 2014075364W WO 2014206137 A1 WO2014206137 A1 WO 2014206137A1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
- B65D81/32—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents for packaging two or more different materials which must be maintained separate prior to use in admixture
- B65D81/3255—Containers provided with a piston or a movable bottom, and permitting admixture within the container
Definitions
- the invention relates to a packaging and delivery system for a freeze-dried preparation and a preparation method thereof.
- the invention relates to a packaging and delivery system for a freeze-dried preparation and a preparation method thereof, in particular to a lyophilized preparation for food, health food, oral medicine, external medicine and cosmetics, and a solvent thereof
- a dual chamber mixer packaging and delivery system that is conveniently stored in the same package, ready to use, and its corresponding method of preparation.
- the lyophilized formulation is a formulation prepared by freeze-drying technique, which is formed by infusion into a molding die and a freeze-drying process. Since the preparation uses the freeze-drying process to protect the heat-sensitive components from being destroyed, the preparation itself generates a large number of micropores and pores, which can be rapidly disintegrated and dissolved, and thus is widely used for application to oral collapse. Tablets, instant release tablets, chewable tablets, special cosmetics and other pharmaceuticals, food, health food and cosmetics.
- the freeze-dried preparations Due to the large number of micropores and pores in the process of freeze-drying the preparation, the freeze-dried preparations have defects such as low strength, easy brittleness and high moisture absorption. Therefore, most of the packaging devices selected for the preparation prepared by the freeze-drying technique are double-aluminum packaging to ensure moisture resistance, oxygen barrier, and the like.
- the double aluminum packaging often does not have good support itself, and needs to be protected by other auxiliary packagings with certain hardness; it is cumbersome to open and use, and brings a certain sense of experience for its products. influences.
- the double aluminum package needs to be opened when it is used, and it can be used after being mixed with the solvent. In the mixing process, the process of opening the package, mixing and exporting the mixed liquid is complicated, and it is easy to mix bacteria, etc. Secondary pollution.
- a packaging and delivery system for a lyophilized formulation of the present invention comprising a lyophilized formulation, a solvent, and a package and delivery device for packaging and delivering the lyophilized formulation and solvent, characterized in that
- the packaging and delivery device is a two-chamber mixer in which the solvent and the lyophilized formulation are separately stored in different chambers of the two-chamber mixer, and the solvent and freeze-drying are imparted by the interaction of the components of the two-chamber mixer.
- Formulations can be mixed and exported immediately upon use.
- the binder is a water-soluble polymer material which is edible, cosmetic or pharmaceutically acceptable, and may be a polysaccharide, a polypeptide, a protein, an artificial polymer, or a modified natural high. Molecular materials or mixtures thereof. Commonly used binders include, but are not limited to, gelatin (gelatin, hydrolyzed gelatin, etc.), cellulose ethers (carboxymethyl cellulose, hydroxyethyl fluorenyl cellulose, etc.), modified starches (pululose) , hydroxypropyl starch, etc.), PVP, PVA, hyaluronic acid, albumin, chitosan and their different molecular weight products or combinations thereof.
- One or more of a drug, a biopharmaceutical, a Chinese herbal extract, a vitamin, a mineral, a cosmetic benefit component, and other active ingredients beneficial to the human body may be selected from the group consisting of one or more of the following: Chemical drugs (pharmaceutical active ingredients):
- Antipyretic analgesic anti-inflammatory drugs such as aspirin, diflunisal, salicylate, acetaminophen, indomethacin, ibuprofen, naproxen, ketoprofen, pirfen, supprofen, fluoride Biprofen, piroxicam, meloxicam, nimesulide, benzbromarone, etc.;
- Central stimulants such as pimoline, aprefini, piracetam, etc.
- migraine drugs such as sumatriptan succinate
- Analgesics such as rotundin, buprenorphine, pentazocine, naloxone, etc.
- Anti-Parkinson's disease and treatment of Alzheimer's drugs such as levodopa, compound carbidopa, compound benserazide, amantadine hydrochloride, piracetil, prolamine, donepezil, huperzine, etc.;
- An abnormal drug such as chlorpromazine, promethazine, pethidine, thioridazine, cloprofen, clozapine, sulpiride, tiapride, penfluridol, risperidone, etc.;
- Antiepileptic and anticonvulsant drugs such as phenytoin, carbamazepine, pumilidone, gabapentin, lamotrigine, sodium valproate, clonazepam, and the like.
- Sedative hypnotics such as diazepam, nitrazepam, oxazepam, lorazepam, phenobarbital, etc.; cholinesterase inhibitors, such as scopolamine;
- Antiarrhythmic drugs such as propionate, tolcanib, mexiletine, ethexazine, phenytoin, propafenone, amine ketone, etc.;
- Anti-angina and anti-atherosclerotic drugs such as propranolol, nifedipine, gemfibrozil, bezafibrate, lovastatin, simvastatin, pravastatin, etc.;
- Antihypertensive drugs such as enalapril, captopril, hydrochlorothiazide, amlodipine; adrenal receptor blockers, such as acebutolol, aplol, etc.;
- Cortic drugs such as betamethasone, cortisone acetate, etc.
- Antidiabetic drugs such as repaglinide
- Anti-sputum gland drugs such as propylthiouracil, carbimabazole, indazole, etc.;
- Antihistamines such as cetirizine hydrochloride, loratadine, etc.;
- Autoactive substances such as denoprostone, alprostadil, betahistine, etc.
- Digestive system medications such as butyl bromide, granisetron hydrochloride, etc.;
- Blood system drugs such as EPO, adenosine cobalamin, etc.
- Urinary system drugs such as azosemide, furosemide, etc.
- Reproductive system drugs such as estrogen, Nandrolone phenylpropionate, etc.
- Antiparasitic drugs such as albendazole, canbendazole, etc.
- Antineoplastic agents such as aminoglutethimide, ampicillin, etc.
- Antimicrobial agents such as ampicillin, sulfacillin sodium, etc.
- Antibiotics such as amoxicillin, cephalexin, cefprozil, cefuroxime axetil, roxithromycin, erythromycin ethylsuccinate, josamycin, etc.;
- Chinese herbal medicine active ingredient monomers such as: breviscapine, artemisinin, etc.;
- Single-flavored Chinese herbal medicine extract and compound Chinese herbal extract such as: tanshinone extract, salvianolic acid extract, compound Danshen dripping pill extract, Niuhuang Shangqing pill compound extract, ginseng stem and leaf total saponin, and northern bean root extract , ginseng total saponins, breviscapine, saponins, swollen wind extract, panax notoginseng saponins, capillaris extract, rhubarb extract, andrographolide, hawthorn leaf extract, centella asiatica ;
- Natural plant extracts such as aloe extract, yam extract, bilberry extract, bitter gourd extract, green tea extract, fucoidan, licorice, paeoniflorin, etc.;
- Biologically active ingredients EGF, bFGF, aFGF, KGF, IGF, PDGF, VEGF, placental hydrolysate, milk extract, and the like.
- the freeze-dried preparation is mainly composed of functional ingredients and binders, and may or may not be added with a skeleton support agent and other auxiliary materials (such as a thickening suspension according to the preparation process). Antioxidants, flavors and flavors, transdermal absorption enhancers, pH adjusters, etc.).
- the skeleton support agent includes amino acids (such as glycine, alanine, glutamic acid, etc.) which are not limited to sugars (such as maltose, trehalose, etc.), sugar alcohols (such as mannitol, sorbitol), and 2-12 carbon atoms. ) and inorganic salts (such as sodium phosphate, aluminum silicate, etc.).
- amino acids such as glycine, alanine, glutamic acid, etc.
- sugars such as maltose, trehalose, etc.
- sugar alcohols such as mannitol, sorbitol
- inorganic salts such as sodium phosphate, aluminum silicate, etc.
- the other excipients include, but are not limited to, thickening suspensions, antioxidants, flavorings and flavors, transdermal absorption enhancers, pH adjusters, etc.; wherein the thickening suspension may be selected from the group consisting of dextran, gum arabic, yellow Raw gum, carrageenan, pectin, konjac gum, agar, carbomer, carrageenan, etc.
- the antioxidants include, but are not limited to, vitamin C and its derivatives, anthocyanins, resveratrol, plant sources a mixture of one or more of the polyphenolic compounds;
- the flavorings and flavors include, but are not limited to, mint, chocolate, vanilla, coffee, tea, corn, lemon, milk, etc.
- the transdermal absorption enhancer includes, but is not limited to, a mixture of any one or more of lecithin, saponin, strontium lauryl amide, azone, tween, and dice
- the pH adjusting agent includes, but is not limited to, a mixture of any one or more of citric acid, tartaric acid, carbonate, sodium carbonate, and phosphate.
- the packaging and delivery device for packaging and delivering the lyophilized formulation and solvent used in the packaging and delivery system of the lyophilized formulation provided by the present invention is any device that can achieve the object of the present invention, Preferably it is a two chamber mixer.
- the dual chamber mixer comprises two chambers (3, 6), two pistons (5, 7), a bypass (4), a push rod handle (10), a discharge device (2), a Discharge cover (1) six parts.
- the two chambers are a solid preparation chamber 3 and a liquid preparation chamber 6; the solid preparation chamber 3 is a cavity near the discharger portion, and the liquid preparation chamber 6 is a cavity away from the discharger portion; it may be a single integral cavity
- the two parts separated by a piston can also be composed of two independent cavities connected by means of bonding (welding), non-fitting (bonding) or form-locking (insertion locking), etc. The way it is connected depends on the overall shape, material and functional needs.
- the lyophilized formulation 9 in the solid preparation chamber 3 may be a lyophilized preparation of various formulations and forms, and is a preparation which is divided into the solid preparation chamber 3 after lyophilization in a molding die;
- the solvent 8 can be water, a nutrient solution having a certain functional ingredient, an essence, and various solvents which can be directly used in combination with the freeze-dried form.
- the bypass 4 is located on the side of the solid preparation chamber and has a width slightly larger than the thickness of the piston 5, so that the solvent in the cavity 6 can be opened by the piston to the bypass 4 to form an opening and freeze-dried in the solid preparation chamber 3.
- Formulation 9 was mixed.
- the pusher presses the hand 10 as a means for applying pressure to the cavity to move the piston.
- the ejector 2 is in the form of a non-injection needle in any form, such as a suction tube, a drop tube, a ball shape, a spray head or the like.
- the discharge cover 1 is a device capable of sealing the mouth of the discharge device to isolate the material in the cavity from the external environment.
- the invention further relates to a process for the preparation of the above lyophilized formulation.
- the lyophilized formulation is prepared by lyophilization in a molding die, demolding and assembling into a solid preparation cavity in a two-chamber mixer, and the preparation method comprises:
- the injection molding volume in the step (a) is 0.01-5.0 ml; wherein the injection molding can use a pipetting device such as a precise quantitative pipette, a pipetting gun, an electronic pipetting gun, or a plunger pump or a gear.
- a pipetting device such as a precise quantitative pipette, a pipetting gun, an electronic pipetting gun, or a plunger pump or a gear.
- the degassing method may employ centrifugal degassing, vacuum degassing, ultrasonic degassing, etc.; wherein the freezing may be carried out using liquid nitrogen or Liquid, solid carbon dioxide spray refrigeration, turbo expander refrigeration or cascade refrigeration, at -20 ° C - 196 ° C temperature, quickly freeze the solution or suspension into a solid;
- the vacuum is from 0.01 to 20 mbar, and the temperature is lyophilized between -70 ° C and 50 ° C.
- the packaging and delivery system is a single-dose package, the amount of liquid is in line with the requirements of the aircraft, easy to carry;
- Figure 1 is an exploded view of the components of the packaging and delivery device (dual chamber mixer) in a packaging and delivery system for a lyophilized formulation;
- Figures 2 - 4 are graphical representations of the steps of use of the packaging and delivery system for a lyophilized formulation.
- the bottom of the cavity referred to in the following embodiments refers to the distal end of the cavity away from the discharge port; the upper side of the bypass 4 refers to the end near the discharge port, and the lower side of the bypass 4 refers to the other side away from the discharge port.
- EGF stock solution after thawing, add gelatin and hydrolyzed gelatin, prepare EGF (weight ratio) containing 5% of 100,000 parts, contain 5% gelatin + hydrolyzed gelatin solution, fill into 0.1 ml molding die, freeze-dry and shape
- the solid preparation chamber 3 of the double-cavity mixer of glass material is then assembled into the bottom of the solid preparation chamber 3 under the bypass 4 by the piston 5 of the rubber material; and 2 ml of the 3% hyaluronic acid solution is filled into the rubber material.
- the piston 5 is separated from the liquid preparation chamber 6; then a rubber-made piston 7 is added, so that the liquid is completely stored in the liquid preparation chamber 6, and does not ooze from between the rubber-made piston 5 and the rubber-made piston 7, that is, A dual chamber mixer packaging device comprising a lyophilized formulation and a solvent is obtained.
- a push rod 10 is loaded into the piston 7, and the push rod 10 is pushed toward the liquid preparation chamber 6.
- the liquid pressure in the liquid preparation chamber 6 drives the piston 5 to move toward the solid preparation chamber 3; when the bottom of the piston 5 moves beyond the bypass 4, the liquid in the liquid preparation chamber 6 is directly wound by the bypass 4 under the pressure of the piston 7.
- Example 2 The aforementioned mixed solution is extruded from the discharger 2, and the shape of the head of the discharger 2 is in the form of a ball, which can be directly applied to the face directly during the extrusion process to become a modern bio-cosmetic.
- Example 2
- a push rod 10 is loaded into the piston 7, and the push rod 10 is pushed to move toward the liquid preparation chamber 6.
- the liquid pressure in the liquid preparation chamber 6 drives the piston 5 to move toward the solid preparation chamber 3; when the bottom of the piston 5 moves beyond the bypass 4 below, the liquid in the liquid preparation chamber 6 under the pressure of the piston 7, directly bypasses the piston 5 through the bypass 4, enters the solid preparation chamber 3, mixes with the freeze-dried shaped preparation, and continues to push the push rod to the piston forward.
- a push rod 10 is loaded into the piston 7, and the push rod 10 is pushed to move toward the liquid preparation chamber 6.
- the liquid pressure in the liquid preparation chamber 6 drives the piston 5 to move toward the solid preparation chamber 3; when the bottom of the piston 5 moves beyond the bypass 4 below, the liquid in the liquid preparation chamber 6 under the pressure of the piston 7, directly bypasses the piston 5 through the bypass 4, enters the solid preparation chamber 3, mixes with the freeze-dried shaped preparation, and continues to push the push rod to the piston forward.
- a push rod 10 is loaded into the piston 7, and the push rod 10 is pushed to move toward the liquid preparation chamber 6.
- the liquid pressure in the liquid preparation chamber 6 drives the piston 5 to move toward the solid preparation chamber 3; when the bottom of the piston 5 moves beyond the bypass 4 below, the liquid in the liquid preparation chamber 6 under the pressure of the piston 7, directly bypasses the piston 5 through the bypass 4, enters the solid preparation chamber 3, mixes with the freeze-dried shaped preparation, and continues to push the push rod to the piston forward.
- the piston 7 allows the liquid to be completely stored in the liquid preparation chamber 6, and does not ooze out between the silicone-made piston 5 and the silicone-made piston 7, thereby obtaining a double-cavity mixer packaging device containing the freeze-dried shaped preparation. .
- the push rod 10 When in use, the push rod 10 is pushed to move toward the liquid preparation chamber 6, and the liquid pressure in the liquid preparation chamber 6 drives the piston 5 to move toward the solid preparation chamber 3; when the bottom portion of the piston 5 moves below the bypass 4, the liquid in the liquid preparation chamber 6 Under the pressure of the piston 7, the piston 5 is directly bypassed by the bypass 4, enters the solid preparation chamber 3, mixes with the lyophilized shaped preparation therein, and continues to push the push rod forward until the top of the piston 7 contacts the bottom of the piston 5, all the liquid 20 ml of deionized water containing natural pigment in the preparation chamber 6 is completely mixed with the freeze-dried shaped preparation to form a solution containing 0.5% of cranberry extract; the discharge cover 1 is opened, the push rod 10 is continuously pushed, and the piston 7 is pressed.
- the piston 5, orally, the above-mentioned mixed solution is orally taken out from the discharge nozzle 2 to form a solid beverage food.
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Abstract
A packing and delivery system for a freeze-dried excipient comprises a freeze-dried excipient (9), a solvent (8), and a packing and delivery apparatus for packing and delivering the freeze-dried excipient and the solvent, where the packing and delivery apparatus is a dual-cavity mixer, the solvent (8) and the freeze-dried excipient (9) are separately saved in different cavities of the dual-cavity mixer, and by means of the mutual effects of members of the dual-cavity mixer, the solvent (8) and the freeze-dried excipient (9) may be mixed and discharged in real time during use. The packing and delivery system for a freeze-dried excipient have advantages such as protection for the stability of active ingredients, an enhanced use effect, reduced potential side reactions, an extended shelf life, single-dosage packing, portability, being pollutionless, use convenience, lowered cost, and the like.
Description
一种冻干赋型制剂的包装和递送系统及其制备方法 本申请要求 2013 年 06 月 24 日提交中国专利局、 申请号为 201310251059.3 ,发明名称为"一种冻干赋型制剂的包装和递送系统及其制 备方法 "的中国专利申请的优先权, 其全部内容通过引用结合在本申请中。 技术领域 The invention relates to a packaging and delivery system for a freeze-dried preparation and a preparation method thereof. The application claims to be submitted to the Chinese Patent Office on June 24, 2013, the application number is 201310251059.3, and the invention is entitled "Packaging and delivery of a freeze-dried preparation" The priority of the Chinese Patent Application, the entire disclosure of which is incorporated herein by reference. Technical field
本发明涉及一种冻干赋型制剂的包装和递送系统及其制备方法, 特别 是一种应用于食品、 保健食品、 口服药品、 外用药品以及化妆品的冻干赋 型制剂的, 将其与溶剂在同一包装内分别保存、 使用时即配即用的双腔混 料器包装和递送系统, 以及其相应的制备方法。 The invention relates to a packaging and delivery system for a freeze-dried preparation and a preparation method thereof, in particular to a lyophilized preparation for food, health food, oral medicine, external medicine and cosmetics, and a solvent thereof A dual chamber mixer packaging and delivery system that is conveniently stored in the same package, ready to use, and its corresponding method of preparation.
背景技术 Background technique
冻干赋型制剂是利用冻干赋型技术制备的一种制剂形态, 其通过灌注 到成型模具中及冷冻干燥的工艺过程成型而成。 由于该类制剂釆用冷冻干 燥工艺, 可以保护热敏感成分不被破坏, 同时制剂本身产生大量微孔和孔 道, 使其可以很快的崩解和溶解, 因此受到了广泛使用, 应用到口腔崩解 片、 速释片、 咀嚼片、 特殊化妆品等药品、 食品、 保健食品及化妆品领域 中。 The lyophilized formulation is a formulation prepared by freeze-drying technique, which is formed by infusion into a molding die and a freeze-drying process. Since the preparation uses the freeze-drying process to protect the heat-sensitive components from being destroyed, the preparation itself generates a large number of micropores and pores, which can be rapidly disintegrated and dissolved, and thus is widely used for application to oral collapse. Tablets, instant release tablets, chewable tablets, special cosmetics and other pharmaceuticals, food, health food and cosmetics.
由于冻干赋型制剂的工艺过程产生大量微孔和孔道的特性, 使冻干赋 型制剂均具有制剂强度不高、 容易脆碎以及极易吸潮等缺陷。 因此冻干赋 型技术制备的制剂所选用的包装装置大多为双铝包装, 以保证其隔潮性、 隔氧性等。 但双铝包装往往本身不具有很好的支撑性, 需要借助其他具有 一定硬度的辅助包装增强对制剂的保护性;其在开启与使用时均较为繁瑣, 为其产品使用的体验感带来一定影响。 且双铝包装在使用时需要开启其包 装, 与其溶剂进行混合后方可使用, 在混合过程中, 开启包装、 混合以及 将混合液导出的过程比较复杂, 并容易混入细菌等造成包装开启后的二次 污染。 Due to the large number of micropores and pores in the process of freeze-drying the preparation, the freeze-dried preparations have defects such as low strength, easy brittleness and high moisture absorption. Therefore, most of the packaging devices selected for the preparation prepared by the freeze-drying technique are double-aluminum packaging to ensure moisture resistance, oxygen barrier, and the like. However, the double aluminum packaging often does not have good support itself, and needs to be protected by other auxiliary packagings with certain hardness; it is cumbersome to open and use, and brings a certain sense of experience for its products. influences. And the double aluminum package needs to be opened when it is used, and it can be used after being mixed with the solvent. In the mixing process, the process of opening the package, mixing and exporting the mixed liquid is complicated, and it is easy to mix bacteria, etc. Secondary pollution.
传统的预灌装式双腔注射器主要用于注射使用用途, 为了避免生产和 使用过程中的微生物和其它污染, 必须在注射器内完成原位冻干后于百级 洁净区内完成包装过程, 大大提高了生产成本; 同时, 由于传统的冷冻干
燥是基于小分子糖类、 糖醇和氨基酸为主的冻干保护剂体系, 其冻干粉形 态对物理机械力非常敏感, 如果不使用原位冻干, 非常容易破碎, 造成剂 量的不准确, 同时破碎或脱落的冻干粉碎片也会给预灌装式双腔注射器的 装配和使用带来很大的问题。 Traditional pre-filled dual-chamber syringes are mainly used for injection purposes. In order to avoid microbial and other contamination during production and use, the in-situ lyophilization must be completed in the syringe to complete the packaging process in the 100-level clean zone. Increased production costs; at the same time, due to traditional freeze-drying Drying is a lyoprotectant system based on small molecular sugars, sugar alcohols and amino acids. Its lyophilized powder form is very sensitive to physical and mechanical forces. If it is not used in situ freeze-drying, it is very easy to break, resulting in inaccurate dosage. Freeze-dried granules that are simultaneously broken or detached can also pose significant problems in the assembly and use of prefilled dual-chamber syringes.
因此, 发明人锐意创新, 为了解决冻干赋型制剂的包装和使用方式, 同时为了开拓非注射式冻干制剂的包装和使用方式, 进行了大量深入的研 究和试验工作, 从而完成了本发明, 提供了一种非注射使用的、 可以在使 用时即配即用、 冻干赋型制剂与其溶剂在同一包装内分开保存, 使用时直 接混合导出的冻干赋型制剂的包装和递送系统及其相应冻干赋型制剂的制 备、 装配方法, 由此完成了本发明。 Therefore, the inventors are keen to innovate, in order to solve the packaging and use of freeze-dried formulations, and in order to open up the packaging and use of non-injectable lyophilized preparations, a lot of intensive research and experimental work has been carried out, thereby completing the present invention. Providing a non-injectable packaging and delivery system for lyophilized excipients which can be used at the time of use, ready-to-use, lyophilized excipients and their solvents are stored separately in the same package, and directly mixed and used at the time of use and The preparation and assembly method of the corresponding freeze-dried excipients, thereby completing the present invention.
发明内容 Summary of the invention
本发明所提供的一种冻干赋型制剂的包装和递送系统, 包括冻干赋型 制剂、 溶剂以及包装和递送所述冻干赋型制剂和溶剂的包装和递送装置, 其特征在于所述包装和递送装置为双腔混料器, 其中溶剂以及冻干赋型制 剂分别保存于双腔混料器的不同腔体中, 通过双腔混料器各部件的相互作 用使溶剂和冻干赋型制剂在使用时可以即时混合并导出。 A packaging and delivery system for a lyophilized formulation of the present invention, comprising a lyophilized formulation, a solvent, and a package and delivery device for packaging and delivering the lyophilized formulation and solvent, characterized in that The packaging and delivery device is a two-chamber mixer in which the solvent and the lyophilized formulation are separately stored in different chambers of the two-chamber mixer, and the solvent and freeze-drying are imparted by the interaction of the components of the two-chamber mixer. Formulations can be mixed and exported immediately upon use.
本发明所提供的冻干赋型制剂的包装和递送系统中所使用的冻干赋型 制剂,其主要由功效成分和粘结剂组成,且粘结剂:功效成分 =1: 10至 10:1。 The lyophilized formulation for use in the packaging and delivery system of the lyophilized formulation provided by the present invention is mainly composed of an efficacy component and a binder, and the binder: efficacy component = 1: 10 to 10: 1.
所述粘结剂是可食用、 可做化妆品用或者可药用的一种水溶性高分子 材料, 可以是多糖、 多肽、 蛋白质、 也可能是人工聚合高分子, 或者是经 过改性的天然高分子材料或其混合物。 常用的粘结剂包括但不限于, 明胶 类(明胶、 水解明胶等)、 纤维素醚类(羧曱基纤维素, 羟乙基曱基纤维素 等)、 改性淀粉类(普鲁兰糖、 羟丙基淀粉等)、 PVP、 PVA、 透明质酸类、 白蛋白、 壳聚糖及其不同分子量产物或它们的组合等。 药物、 生物药物、 中药提取物、 维生素、 矿物质、 化妆有益成分和其它对 人体有益的活性成分中的一种或一种以上; 可以选自下列一种或几种成分 的组合物:
化学药物( 药物活性成分) : The binder is a water-soluble polymer material which is edible, cosmetic or pharmaceutically acceptable, and may be a polysaccharide, a polypeptide, a protein, an artificial polymer, or a modified natural high. Molecular materials or mixtures thereof. Commonly used binders include, but are not limited to, gelatin (gelatin, hydrolyzed gelatin, etc.), cellulose ethers (carboxymethyl cellulose, hydroxyethyl fluorenyl cellulose, etc.), modified starches (pululose) , hydroxypropyl starch, etc.), PVP, PVA, hyaluronic acid, albumin, chitosan and their different molecular weight products or combinations thereof. One or more of a drug, a biopharmaceutical, a Chinese herbal extract, a vitamin, a mineral, a cosmetic benefit component, and other active ingredients beneficial to the human body; may be selected from the group consisting of one or more of the following: Chemical drugs (pharmaceutical active ingredients):
解热镇痛抗炎药, 例如阿司匹林、 二氟尼柳、 双水杨酯、 对乙酰氨基酚、 吲哚美辛、 布洛芬、 萘普生、 酮洛芬、 吡洛芬、 舒洛芬、 氟比洛芬、 吡罗 昔康、 美洛昔康、 尼美舒利、 苯溴马隆等; Antipyretic analgesic anti-inflammatory drugs, such as aspirin, diflunisal, salicylate, acetaminophen, indomethacin, ibuprofen, naproxen, ketoprofen, pirfen, supprofen, fluoride Biprofen, piroxicam, meloxicam, nimesulide, benzbromarone, etc.;
中枢兴奋药, 例如匹莫林、 阿屈非尼、 吡拉西坦等; Central stimulants, such as pimoline, aprefini, piracetam, etc.;
治疗偏头痛药, 例如琥珀酸舒马普坦; Treatment of migraine drugs, such as sumatriptan succinate;
镇痛药, 例如罗通定、 丁丙诺啡、 喷他佐辛、 纳洛酮等; Analgesics, such as rotundin, buprenorphine, pentazocine, naloxone, etc.;
抗帕金森病和治疗老年痴呆药, 例如左旋多巴、 复方卡比多巴、 复方苄丝 肼、 盐酸金刚烷胺、 吡贝地尔、 普罗酚胺、 多奈哌齐、 石杉碱曱等; 抗精神失常药, 例如氯丙嗪、 异丙嗪、 哌替啶、 硫利达嗪、 氯普噻吨、 氯 氮平、 舒必利、 泰必利、 五氟利多、 利培酮等; Anti-Parkinson's disease and treatment of Alzheimer's drugs, such as levodopa, compound carbidopa, compound benserazide, amantadine hydrochloride, piracetil, prolamine, donepezil, huperzine, etc.; An abnormal drug, such as chlorpromazine, promethazine, pethidine, thioridazine, cloprofen, clozapine, sulpiride, tiapride, penfluridol, risperidone, etc.;
抗癲痫病和抗惊厥药, 例如苯妥英钠、 卡马西平、 朴米酮、 加巴喷丁、 拉 莫三嗪、 丙戊酸钠、 氯硝西泮等。 Antiepileptic and anticonvulsant drugs, such as phenytoin, carbamazepine, pumilidone, gabapentin, lamotrigine, sodium valproate, clonazepam, and the like.
镇静催眠药, 例如地西泮、 硝西泮、 奥沙西泮、 劳拉西泮、 苯巴比妥等; 胆碱酯酶抑制药, 例如东莨菪碱等; Sedative hypnotics, such as diazepam, nitrazepam, oxazepam, lorazepam, phenobarbital, etc.; cholinesterase inhibitors, such as scopolamine;
抗心律失常药, 例如丙吡啶、 妥卡尼、 美西律、 乙吗噻嗪、 苯妥英钠、 普 罗帕酮、 胺破酮等; Antiarrhythmic drugs, such as propionate, tolcanib, mexiletine, ethexazine, phenytoin, propafenone, amine ketone, etc.;
抗心绞痛与抗动脉粥样硬化药, 例如普萘洛尔、 硝苯地平、 吉非贝齐、 苯 扎贝特、 洛伐他汀、 辛伐他汀、 普伐他汀等; Anti-angina and anti-atherosclerotic drugs, such as propranolol, nifedipine, gemfibrozil, bezafibrate, lovastatin, simvastatin, pravastatin, etc.;
抗高血压药, 例如依拉普利、 卡托普利、 氢氯噻嗪、 氨氯地平等; 肾上腺受体阻断剂, 例如醋丁洛尔、 阿普洛尔等; Antihypertensive drugs, such as enalapril, captopril, hydrochlorothiazide, amlodipine; adrenal receptor blockers, such as acebutolol, aplol, etc.;
皮质 类药, 例如倍他米松、 醋酸可的松等; Cortic drugs, such as betamethasone, cortisone acetate, etc.;
抗糖尿病药, 例如瑞格列奈等; Antidiabetic drugs, such as repaglinide;
抗曱状腺药, 例如丙硫氧嘧啶、 卡比马唑、 曱巯咪唑等; Anti-sputum gland drugs, such as propylthiouracil, carbimabazole, indazole, etc.;
抗组织胺药, 例如盐酸西替利嗪、 氯雷他定等; Antihistamines, such as cetirizine hydrochloride, loratadine, etc.;
自体活性物质, 例如地诺前列酮、 前列地尔、 倍他司汀等; Autoactive substances, such as denoprostone, alprostadil, betahistine, etc.;
消化系统用药, 例如丁溴东莨菪碱、 盐酸格拉司琼等; Digestive system medications, such as butyl bromide, granisetron hydrochloride, etc.;
血液系统药, 例如 EPO、 腺苷钴胺等; Blood system drugs, such as EPO, adenosine cobalamin, etc.;
泌尿系统药, 例如阿佐塞米、 呋塞米等; Urinary system drugs, such as azosemide, furosemide, etc.;
生殖系统药, 例如雌激素、 苯丙酸诺龙等;
抗寄生虫药, 例如阿苯达唑、 坎苯达唑等; Reproductive system drugs, such as estrogen, Nandrolone phenylpropionate, etc.; Antiparasitic drugs, such as albendazole, canbendazole, etc.;
抗肿瘤药, 例如氨鲁米特、 安吖啶等; Antineoplastic agents, such as aminoglutethimide, ampicillin, etc.;
抗微生物药, 例如氨苄西林、 磺苄西林钠等; Antimicrobial agents, such as ampicillin, sulfacillin sodium, etc.;
抗生素类药, 例如阿莫西林、 头孢氨苄、 头孢丙烯、 头孢呋辛酯、 罗红霉 素、 琥乙红霉素、 交沙霉素等; Antibiotics such as amoxicillin, cephalexin, cefprozil, cefuroxime axetil, roxithromycin, erythromycin ethylsuccinate, josamycin, etc.;
中药成分: Chinese medicine ingredients:
中药有效成分单体, 如: 灯盏花素、 青蒿素等; Chinese herbal medicine active ingredient monomers, such as: breviscapine, artemisinin, etc.;
单味中药材提取物及复方中药提取物, 如: 丹参酮提取物、 丹参总酚酸提 取物、 复方丹参滴丸提取物、 牛黄上清丸复方提取物、 人参茎叶总皂苷、 北豆根提取物、 人参总皂苷、 灯盏花素、 三七三醇皂苷、 肿节风浸膏、 三 七总皂苷、 茵陈提取物、 大黄浸膏、 穿心莲内酯、 山楂叶提取物、 积雪草 总苷等; Single-flavored Chinese herbal medicine extract and compound Chinese herbal extract, such as: tanshinone extract, salvianolic acid extract, compound Danshen dripping pill extract, Niuhuang Shangqing pill compound extract, ginseng stem and leaf total saponin, and northern bean root extract , ginseng total saponins, breviscapine, saponins, swollen wind extract, panax notoginseng saponins, capillaris extract, rhubarb extract, andrographolide, hawthorn leaf extract, centella asiatica ;
天然植物提取物: 如芦荟提取物、 山药提取物、 越橘提取物、 苦瓜提取物、 绿茶提取物、 岩藻多糖、 光甘草定、 芍药苷等; Natural plant extracts: such as aloe extract, yam extract, bilberry extract, bitter gourd extract, green tea extract, fucoidan, licorice, paeoniflorin, etc.;
生物活性成分: EGF、 bFGF、 aFGF、 KGF、 IGF、 PDGF、 VEGF、 胎盘水 解液、 牛奶提取物等。 Biologically active ingredients: EGF, bFGF, aFGF, KGF, IGF, PDGF, VEGF, placental hydrolysate, milk extract, and the like.
化妆有益成分: 胶原蛋白、 透明质酸、 海藻酸钠、 芦荟提取物、 人参总皂 苷、 三七总皂苷、 大黄提取物、 竹莲水百合提取物、 芍药提取物、 EGF、 bFGF、 aFGF、 KGF、 IGF、 PDGF、 VEGF、 胎盘水解液、 牛奶提取物、 各 类表面活性剂、 藻类提取物、 各种维生素、 各种有益矿物质、 SOD、 金属 硫蛋白、 其他原料见于《国际化妆品原料标准中文名称目录(2010年版)》 所述冻干赋型制剂, 其主要由功效成分、 粘结剂组成, 并根据制剂工 艺需要可添加或不添加骨架支持剂以及其它辅料(如增稠混悬剂、 抗氧化 剂、 矫味剂和香精、 透皮吸收促进剂、 pH调节剂等)。 Make-up beneficial ingredients: collagen, hyaluronic acid, sodium alginate, aloe extract, ginseng total saponin, panax notoginseng saponins, rhubarb extract, bamboo lotus water lily extract, peony extract, EGF, bFGF, aFGF, KGF , IGF, PDGF, VEGF, placental hydrolysate, milk extract, various surfactants, algae extracts, various vitamins, various beneficial minerals, SOD, metallothionein, other raw materials found in "International Cosmetic Ingredients Standard Chinese" Name list (2010 edition) The freeze-dried preparation is mainly composed of functional ingredients and binders, and may or may not be added with a skeleton support agent and other auxiliary materials (such as a thickening suspension according to the preparation process). Antioxidants, flavors and flavors, transdermal absorption enhancers, pH adjusters, etc.).
所述的骨架支持剂包含并不限于糖(如麦芽糖、 海藻糖等)、 糖醇(如 甘露醇、 山梨醇)、 2-12碳原子的氨基酸(如甘氨酸、 丙氨酸、 谷氨酸等) 以及无机盐 (如磷酸钠、 硅酸铝等)等物质。 The skeleton support agent includes amino acids (such as glycine, alanine, glutamic acid, etc.) which are not limited to sugars (such as maltose, trehalose, etc.), sugar alcohols (such as mannitol, sorbitol), and 2-12 carbon atoms. ) and inorganic salts (such as sodium phosphate, aluminum silicate, etc.).
所述的其它辅料包含但不限于增稠混悬剂、抗氧化剂、矫味剂及香精、 透皮吸收促进剂、 pH调节剂等; 其中增稠混悬剂可选自右旋糖酐、 阿拉伯 胶、 黄原胶、 卡拉胶、 果胶、 魔芋胶、 琼脂、 卡波姆、 角叉菜胶等天然来
源胶类和合成高分子化合物以及其他多肽或多糖中的任一种或它们的组合 等; 所述抗氧化剂包括但不限于维生素 C及其衍生物、花青素、 白藜芦醇、 植物来源的多元酚类化合物中的一种或数种的混合物; 所述矫味剂和香精 包括但不限于薄荷味、 巧克力味、 香草味、 咖啡味、 茶味、 玉米味、 柠檬 味、 牛奶味等香精或以上一种或几种香味的混合物; 所述透皮吸收促进剂 包括但不限于卵磷脂、 皂苷、 月桂醇酸呐、 氮酮、 吐温、 司盘中的任一种 或数种的混合物; 所述 pH调节剂包括但不限于柠檬酸、 酒石酸、 碳酸盐、 碳酸钠、 磷酸盐中的任何一种或数种的混合物。 The other excipients include, but are not limited to, thickening suspensions, antioxidants, flavorings and flavors, transdermal absorption enhancers, pH adjusters, etc.; wherein the thickening suspension may be selected from the group consisting of dextran, gum arabic, yellow Raw gum, carrageenan, pectin, konjac gum, agar, carbomer, carrageenan, etc. Any one of a source gum and a synthetic polymer compound and other polypeptides or polysaccharides or a combination thereof; the antioxidants include, but are not limited to, vitamin C and its derivatives, anthocyanins, resveratrol, plant sources a mixture of one or more of the polyphenolic compounds; the flavorings and flavors include, but are not limited to, mint, chocolate, vanilla, coffee, tea, corn, lemon, milk, etc. Or a mixture of one or more of the above flavors; the transdermal absorption enhancer includes, but is not limited to, a mixture of any one or more of lecithin, saponin, strontium lauryl amide, azone, tween, and dice The pH adjusting agent includes, but is not limited to, a mixture of any one or more of citric acid, tartaric acid, carbonate, sodium carbonate, and phosphate.
本发明所提供的冻干赋型制剂的包装和递送系统中所使用的用于包装 和递送所述冻干赋型制剂和溶剂的包装和递送装置为可以实现本发明目的 的任何一种装置, 优选其为一种双腔混料器。 The packaging and delivery device for packaging and delivering the lyophilized formulation and solvent used in the packaging and delivery system of the lyophilized formulation provided by the present invention is any device that can achieve the object of the present invention, Preferably it is a two chamber mixer.
所述双腔混料器, 包括二腔体(3、 6 )、 二活塞(5、 7 )、 一旁路(4 )、 一推杆按手 (10 )、 一出料器(2 )、 一出料盖 (1 ) 六部分。 The dual chamber mixer comprises two chambers (3, 6), two pistons (5, 7), a bypass (4), a push rod handle (10), a discharge device (2), a Discharge cover (1) six parts.
所述二腔体为固体制剂腔 3和液体制剂腔 6; 固体制剂腔 3为靠近出 料器部分的腔体, 液体制剂腔 6为远离出料器部分的腔体; 其可以为单个 整体腔体通过活塞分隔成的两个部分, 也可由两个独立腔体连接在一起组 成, 其连接方式包含粘合(焊接)、 非形锁合(粘接)或形锁合(插入锁合) 等方式, 其连接方式取决于整体形状、 材料以及功能需要。 The two chambers are a solid preparation chamber 3 and a liquid preparation chamber 6; the solid preparation chamber 3 is a cavity near the discharger portion, and the liquid preparation chamber 6 is a cavity away from the discharger portion; it may be a single integral cavity The two parts separated by a piston can also be composed of two independent cavities connected by means of bonding (welding), non-fitting (bonding) or form-locking (insertion locking), etc. The way it is connected depends on the overall shape, material and functional needs.
固体制剂腔 3中的冻干赋型制剂 9可以是各种配方、 形态的冻干赋型 制剂, 为在成型模具中进行冻干后分装入固体制剂腔 3中的制剂; 液体制 剂腔 6中的溶剂 8可以为水、 具有一定功效成分的营养液、 精华液及可与 冻干赋型直接配合使用的各种溶剂。 The lyophilized formulation 9 in the solid preparation chamber 3 may be a lyophilized preparation of various formulations and forms, and is a preparation which is divided into the solid preparation chamber 3 after lyophilization in a molding die; The solvent 8 can be water, a nutrient solution having a certain functional ingredient, an essence, and various solvents which can be directly used in combination with the freeze-dried form.
所述一旁路 4, 位于固体制剂腔侧面, 其宽度略大于活塞 5的厚度, 可使腔体 6中的溶剂通过活塞运动至旁路 4处时形成开口从而与固体制剂 腔 3中的冻干赋型制剂 9进行混合。 The bypass 4 is located on the side of the solid preparation chamber and has a width slightly larger than the thickness of the piston 5, so that the solvent in the cavity 6 can be opened by the piston to the bypass 4 to form an opening and freeze-dried in the solid preparation chamber 3. Formulation 9 was mixed.
所述一推杆按手 10, 为向腔体施加压力以使活塞运动的装置。 The pusher presses the hand 10 as a means for applying pressure to the cavity to move the piston.
所述一出料器 2, 为非注射针头形式的任意形态出料口, 如吸管状、 滴管状、 滚珠状、 喷雾头等形态。 The ejector 2 is in the form of a non-injection needle in any form, such as a suction tube, a drop tube, a ball shape, a spray head or the like.
所述一出料盖 1, 为可密封出料器口的装置, 使腔体内物质与外界环 境隔离。
本发明还涉及上述冻干赋型制剂的制备方法。 The discharge cover 1 is a device capable of sealing the mouth of the discharge device to isolate the material in the cavity from the external environment. The invention further relates to a process for the preparation of the above lyophilized formulation.
所述冻干赋型制剂的制备是在成型模具中冻干后脱模并装配入双腔混 料器中的固体制剂腔体中包装, 制备方法包括: The lyophilized formulation is prepared by lyophilization in a molding die, demolding and assembling into a solid preparation cavity in a two-chamber mixer, and the preparation method comprises:
( a )将功效成分、 粘结剂及其它辅料配制成溶液、 乳浊液或者悬浮液 注模; 或将固体功效成分注模, 再加入粘结剂及其它辅料配成溶液、 乳浊 液或悬浮液; (a) Formulating functional ingredients, binders and other excipients into solutions, emulsions or suspensions; or molding solid functional ingredients, adding binders and other excipients to form solutions, emulsions or suspension;
( b )将(a )得到的溶液或悬浮液在定量成型模具中进行脱气; (b) degassing the solution or suspension obtained in (a) in a quantitative forming mold;
( c )将(b )得到的脱气后的溶液、 乳浊液或悬浮液或直接将(a )得 到的溶液乳浊液或悬浮液、 在低温下冷冻; (c) the degassed solution, emulsion or suspension obtained in (b) or directly obtained the emulsion or suspension of the solution obtained in (a) at a low temperature;
( d )将(c )得到的制剂在定量成型模具中冷冻干燥、 除去溶剂, 得 到冻干赋型制剂; (d) lyophilizing the preparation obtained in (c) in a quantitative molding die, removing the solvent, and obtaining a freeze-dried formulation;
( e )将(d )得到的冻干赋型制剂脱离成型模具并装入包装装置或其 成型模具就是其中一个腔体, 以此直接进行装配。 (e) The lyophilized formulation obtained in (d) is taken out of the molding die and loaded into a packaging device or a molding die thereof, which is one of the cavities, thereby directly assembling.
其中步骤(a )所述注模体积为 0.01-5.0ml; 其中注模可以釆用精确定 量移液管、 移液枪、 电子移液枪等移液装置, 也可釆用柱塞泵、 齿轮泵、 蠕动泵等, 将配置好的溶液或悬浮液注入定量成型模具; 其中脱气方法可 以釆用离心脱气法、 真空脱气法以及超声脱气法等; 其中冷冻可以釆用液 氮或液体、 固体二氧化碳喷淋制冷的方式, 透平膨胀机制冷方式或复叠制 冷方式, 在 -20°C--196°C温度下, 迅速将溶液或悬浮液冷冻成为固体; 其中 冻干釆用 0.01-20毫巴的真空度, 温度在 -70°C-50°C范围之间冻干。 Wherein the injection molding volume in the step (a) is 0.01-5.0 ml; wherein the injection molding can use a pipetting device such as a precise quantitative pipette, a pipetting gun, an electronic pipetting gun, or a plunger pump or a gear. Pump, peristaltic pump, etc., inject the configured solution or suspension into the quantitative forming mold; wherein the degassing method may employ centrifugal degassing, vacuum degassing, ultrasonic degassing, etc.; wherein the freezing may be carried out using liquid nitrogen or Liquid, solid carbon dioxide spray refrigeration, turbo expander refrigeration or cascade refrigeration, at -20 ° C - 196 ° C temperature, quickly freeze the solution or suspension into a solid; The vacuum is from 0.01 to 20 mbar, and the temperature is lyophilized between -70 ° C and 50 ° C.
本发明的有益效果为: The beneficial effects of the invention are:
1.保护活性成分的稳定性: 通过这种包装和递送系统, 实现了固体和液 体分开, 高活性物质稳定性往往不好, 以固体形态保存, 其稳定性大大提 高, 会提高使用效果、 降低潜在的副反应、 延长货架期; 1. Protection of the stability of the active ingredient: Through the packaging and delivery system, the solid and liquid are separated, the stability of the high active substance is often not good, and the solid form is preserved, the stability is greatly improved, the use effect is improved, and the effect is lowered. Potential side effects, extended shelf life;
2.单剂量包装: 与常规的多计量产品相比,该包装和递送系统是单剂量 包装, 其液体量符合飞机随身携带要求, 便于携带; 2. Single-dose packaging: Compared with conventional multi-metering products, the packaging and delivery system is a single-dose package, the amount of liquid is in line with the requirements of the aircraft, easy to carry;
3.避免污染: 与传统的冻干赋形双铝包装和传统双瓶装冻干粉形态相 比, 该包装和递送系统所有组装过程在洁净生产区内完成, 没有暴露部件 只从出料口挤出, 不会造成配制过程中的微生物污染;
4.使用方便: 与传统的冻干赋形双铝包装相比, 该包装和递送系统, 无 需揭开包装, 放入掌中, 再加入液体, 以手指混匀的双手配合的复杂使用 方式, 只需一推, 打开出料口两个动作即可使用, 非常方便; 3. Avoid contamination: Compared with the traditional freeze-dried double-aluminum package and the traditional double-bottle lyophilized powder form, all the assembly process of the packaging and delivery system is completed in the clean production area, and no exposed parts are only squeezed from the discharge port. Out, will not cause microbial contamination during the preparation process; 4. Easy to use: Compared with the traditional freeze-dried double-aluminum packaging, the packaging and delivery system does not need to unpack the package, put it into the palm, add liquid, and use the fingers to mix the complicated use of the hands. Need to push, open the discharge port two actions can be used, very convenient;
5.降低成本: 与冻干粉相比, 没有复杂的双瓶和瓶盖系统; 与传统的冻 干赋形双铝包装相比, 没有复杂的支撑和结构设计, 完全自动化包装, 大 幅降低生产成本。 5. Reduced costs: Compared with lyophilized powder, there is no complicated double bottle and cap system; compared with traditional freeze-dried double-aluminum packaging, there is no complicated support and structural design, fully automated packaging, and greatly reduced production. cost.
附图说明 DRAWINGS
图 1为冻干赋型制剂的包装和递送系统中包装和递送装置 (双腔混料 器)各部件分解图; Figure 1 is an exploded view of the components of the packaging and delivery device (dual chamber mixer) in a packaging and delivery system for a lyophilized formulation;
图 2-图 4为冻干赋型制剂的包装和递送系统的使用步骤图解。 Figures 2 - 4 are graphical representations of the steps of use of the packaging and delivery system for a lyophilized formulation.
具体实施方式 detailed description
以下通过实施例进一步说明本发明, 但本发明并不仅仅限于此。 The invention is further illustrated by the following examples, but the invention is not limited thereto.
以下实施例所指的腔体的底部, 是指腔体远离出料口的远端; 旁路 4 的上方是指靠近出料口的一端, 旁路 4的下方是指远离出料口的另一端; 活塞的顶部是指活塞靠近出料口的一端, 活塞的底部是指活塞远离出料口 的另一端。 实施例 1 : The bottom of the cavity referred to in the following embodiments refers to the distal end of the cavity away from the discharge port; the upper side of the bypass 4 refers to the end near the discharge port, and the lower side of the bypass 4 refers to the other side away from the discharge port. One end; the top of the piston refers to the end of the piston near the discharge port, and the bottom of the piston refers to the other end of the piston away from the discharge port. Example 1
EGF原液, 解冻后加入明胶、 水解明胶, 配制成含十万分之五的 EGF (重量比)、 含 5%的明胶 +水解明胶溶液, 灌装进入 0.1毫升成型模具, 冻 干成型后装入玻璃材质的双腔混料器的固体制剂腔 3, 然后将橡胶材质的 活塞 5装配入固体制剂腔 3底部、 旁路 4下方; 再将 3%的透明质酸溶液 2 毫升灌装入橡胶材质的活塞 5隔离出的液体制剂腔 6; 之后加入橡胶材质 的活塞 7, 使液体完整保存于液体制剂腔 6 内, 不会从橡胶材质的活塞 5 和橡胶材质的活塞 7之间渗出, 即得到包含冻干赋形制剂和溶剂的双腔混 料器包装装置。 EGF stock solution, after thawing, add gelatin and hydrolyzed gelatin, prepare EGF (weight ratio) containing 5% of 100,000 parts, contain 5% gelatin + hydrolyzed gelatin solution, fill into 0.1 ml molding die, freeze-dry and shape The solid preparation chamber 3 of the double-cavity mixer of glass material is then assembled into the bottom of the solid preparation chamber 3 under the bypass 4 by the piston 5 of the rubber material; and 2 ml of the 3% hyaluronic acid solution is filled into the rubber material. The piston 5 is separated from the liquid preparation chamber 6; then a rubber-made piston 7 is added, so that the liquid is completely stored in the liquid preparation chamber 6, and does not ooze from between the rubber-made piston 5 and the rubber-made piston 7, that is, A dual chamber mixer packaging device comprising a lyophilized formulation and a solvent is obtained.
使用时将一推杆 10装入活塞 7, 推动推杆 10向液体制剂腔 6方向运
动, 液体制剂腔 6内液体压力带动活塞 5向固体制剂腔 3方向运动; 当活 塞 5底部运动超过旁路 4下方时, 液体制剂腔 6内液体在活塞 7压力下, 通过旁路 4直接绕开活塞 5,进入固体制剂腔 3, 与其中的冻干赋形制剂混 合, 继续向前推动推杆至活塞 7顶部与活塞 5底部接触, 全部液体制剂腔 6内 2毫升 3%的透明质酸溶液完全与冻干赋形制剂混合,形成含有 2.5ppm 的 EGF、 0.25%明胶 +水解明胶、 3%透明质酸的溶液; 打开出料盖 1, 继续 推动推杆 10, 带动活塞 7紧压活塞 5,将前述的混合溶液从出料器 2挤出, 出料器 2头部形状为滚珠形态, 在挤出过程中可以直接均匀涂于脸部, 成 为现代生物化妆品。 实施例 2: In use, a push rod 10 is loaded into the piston 7, and the push rod 10 is pushed toward the liquid preparation chamber 6. The liquid pressure in the liquid preparation chamber 6 drives the piston 5 to move toward the solid preparation chamber 3; when the bottom of the piston 5 moves beyond the bypass 4, the liquid in the liquid preparation chamber 6 is directly wound by the bypass 4 under the pressure of the piston 7. Open the piston 5, enter the solid preparation chamber 3, mix with the freeze-dried shaped preparation, continue to push the push rod forward until the top of the piston 7 is in contact with the bottom of the piston 5, and 2 ml of 3% hyaluronic acid in the entire liquid preparation chamber 6 The solution is completely mixed with the lyophilized shaped preparation to form a solution containing 2.5 ppm of EGF, 0.25% gelatin + hydrolyzed gelatin, 3% hyaluronic acid; opening the discharge cover 1, continuing to push the push rod 10, and driving the piston 7 to press the piston 5. The aforementioned mixed solution is extruded from the discharger 2, and the shape of the head of the discharger 2 is in the form of a ball, which can be directly applied to the face directly during the extrusion process to become a modern bio-cosmetic. Example 2:
维生素 C : 普鲁兰 =5: 1, 混合后的粉末 50mg以固体形式灌装进入 0.4 毫升成型模具, 然后将剩余的 10mg以 0.4毫升水溶解后, 灌装进含有 粉末的成型模具, 冻干后将获得的冻干赋形制剂装入带有旁路 4的塑料材 质的双腔混料器的固体制剂腔 3中, 然后将硅胶材质的活塞 5装配入塑料 材质的固体制剂腔 3底部、 旁路 4下方。 Vitamin C: Pullulan = 5: 1, 50 mg of the mixed powder is filled in a solid form into a 0.4 ml molding die, and then the remaining 10 mg is dissolved in 0.4 ml of water, and then filled into a molding die containing the powder, and lyophilized. Then, the obtained freeze-dried shaped preparation is filled into the solid preparation chamber 3 of the plastic double-cavity mixer with the bypass 4, and then the silicone-made piston 5 is assembled into the bottom of the solid preparation chamber 3 of the plastic material, Bypass 4 below.
将去离子水 2毫升灌装入硅胶材质的活塞 7隔离出的塑料材质的液体 制剂腔 6; 之后将塑料材质的固体制剂腔 3插入塑料材质的液体制剂腔 6, 并以超声波将两个腔体焊接在一起, 即得到包含冻干赋形制剂的塑料材质 的双腔混料器包装装置。 2 ml of deionized water is poured into the liquid preparation chamber 6 of the plastic material separated by the piston 7 of the silicone material; then the solid preparation chamber 3 of the plastic material is inserted into the liquid preparation chamber 6 of the plastic material, and the two chambers are ultrasonically irradiated. The bodies are welded together to obtain a plastic double-cavity mixer packaging device comprising a freeze-dried shaped preparation.
使用时将一推杆 10装入活塞 7, 推动推杆 10向液体制剂腔 6方向运 动, 液体制剂腔 6内液体压力带动活塞 5向固体制剂腔 3方向运动; 当活 塞 5底部运动超过旁路 4下方时, 液体制剂腔 6内液体在活塞 7压力下, 通过旁路 4直接绕开活塞 5,进入固体制剂腔 3, 与其中的冻干赋形制剂混 合, 继续向前推动推杆至活塞 7顶部与活塞 5底部接触, 全部液体制剂腔 6内 2毫升去离子水完全与冻干赋形制剂混合, 形成含有 2.5%维生素 C的 溶液; 打开出料盖 1, 继续推动推杆 10, 带动活塞 7紧压活塞 5, 将前述 的混合溶液从出料器 2挤出, 直接涂于脸部, 成为现代化妆品。 实施例 3:
虫草提取物: 胶原蛋白 =1克: 5克, 配制成悬浊液溶液, 灌注进入 5毫 升成型模具, 冻干后将获得的冻干赋形制剂装入带有旁路 4的复合铝材质 的双腔混料器的固体制剂腔 3中, 然后将丁基橡胶材质的活塞 5装配入复 合铝材质的的固体制剂腔 3底部、 旁路 4下方。 In use, a push rod 10 is loaded into the piston 7, and the push rod 10 is pushed to move toward the liquid preparation chamber 6. The liquid pressure in the liquid preparation chamber 6 drives the piston 5 to move toward the solid preparation chamber 3; when the bottom of the piston 5 moves beyond the bypass 4 below, the liquid in the liquid preparation chamber 6 under the pressure of the piston 7, directly bypasses the piston 5 through the bypass 4, enters the solid preparation chamber 3, mixes with the freeze-dried shaped preparation, and continues to push the push rod to the piston forward. 7 The top is in contact with the bottom of the piston 5, and 2 ml of deionized water in the entire liquid preparation chamber 6 is completely mixed with the freeze-dried shaped preparation to form a solution containing 2.5% of vitamin C; the discharge cover 1 is opened, and the push rod 10 is continuously pushed to drive The piston 7 presses the piston 5, and the aforementioned mixed solution is extruded from the discharge device 2 and directly applied to the face to become a modern cosmetic. Example 3: Cordyceps extract: Collagen = 1 g: 5 g, formulated into a suspension solution, poured into a 5 ml forming mold, and lyophilized, the obtained freeze-dried shaped preparation is filled with a composite aluminum material with a bypass 4 In the solid preparation chamber 3 of the two-chamber mixer, the butyl rubber piston 5 is then assembled into the bottom of the solid preparation chamber 3 of the composite aluminum material, below the bypass 4.
将含有天然香精的去离子水 10毫升灌装入丁基橡胶材质的活塞 7隔离 出的复合铝材质的液体制剂腔 6; 之后将复合铝材质的固体制剂腔 3插入 复合铝材质的液体制剂腔 6, 并以高温将两个腔体焊接在一起, 即得到包 含冻干赋形制剂的复合铝材质的双腔混料器包装装置。 10 ml of deionized water containing natural flavor is filled into a composite aluminum liquid preparation chamber 6 separated by a butyl rubber piston 7; then the composite aluminum solid preparation chamber 3 is inserted into a composite aluminum liquid preparation chamber. 6. The two cavities are welded together at a high temperature to obtain a double-cavity mixer packaging device comprising a composite aluminum material containing a freeze-dried shaped preparation.
使用时将一推杆 10装入活塞 7, 推动推杆 10向液体制剂腔 6方向运 动, 液体制剂腔 6内液体压力带动活塞 5向固体制剂腔 3方向运动; 当活 塞 5底部运动超过旁路 4下方时, 液体制剂腔 6内液体在活塞 7压力下, 通过旁路 4直接绕开活塞 5,进入固体制剂腔 3, 与其中的冻干赋形制剂混 合, 继续向前推动推杆至活塞 7顶部与活塞 5底部接触, 全部液体制剂腔 6内 10毫升去离子水完全与冻干赋形制剂混合, 形成含有虫草提取物和胶 原蛋白的溶液; 打开出料盖 1, 继续推动推杆 10, 带动活塞 7紧压活塞 5, 将前述的混合溶液从出料器 2挤出, 直接口服, 成为保健食品。 实施例 4: In use, a push rod 10 is loaded into the piston 7, and the push rod 10 is pushed to move toward the liquid preparation chamber 6. The liquid pressure in the liquid preparation chamber 6 drives the piston 5 to move toward the solid preparation chamber 3; when the bottom of the piston 5 moves beyond the bypass 4 below, the liquid in the liquid preparation chamber 6 under the pressure of the piston 7, directly bypasses the piston 5 through the bypass 4, enters the solid preparation chamber 3, mixes with the freeze-dried shaped preparation, and continues to push the push rod to the piston forward. 7 The top is in contact with the bottom of the piston 5, and 10 ml of deionized water in the entire liquid preparation chamber 6 is completely mixed with the freeze-dried shaped preparation to form a solution containing the cordyceps extract and collagen; the discharge cover 1 is opened, and the push rod 10 is continuously pushed. The piston 7 is driven to press the piston 5, and the aforementioned mixed solution is extruded from the discharge device 2 and directly taken orally to become a health food. Example 4:
三七总皂苷: PVP=30mg:15mg, 配制成溶液, 灌装入 0.3ml成型模具, 冻干后装入复合铝材质的双腔混料器的固体制剂腔 3, 然后将硅胶材质的 活塞 5装配入固体制剂腔 3底部、 旁路 4下方; 再将天然香精的去离子水 1毫升灌装入硅胶材质的活塞 5隔离出的液体制剂腔 6;之后加入硅胶材质 的活塞 7, 使液体完整保存于液体制剂腔 6 内, 不会从硅胶材质的活塞 5 和硅胶材质的活塞 7之间渗出, 即得到包含冻干赋形制剂的双腔混料器包 装装置。 Panax notoginseng saponins: PVP = 30mg: 15mg, formulated into a solution, filled into a 0.3ml molding die, lyophilized, filled into a solid cavity 3 of a composite aluminum double-cavity mixer, and then a silicone-made piston 5 Assembled into the bottom of the solid preparation chamber 3, below the bypass 4; then 1 ml of deionized water of natural flavor is filled into the liquid preparation chamber 6 separated by the piston 5 of the silicone material; then the piston 7 of the silicone material is added to complete the liquid It is stored in the liquid preparation chamber 6 and does not ooze out between the piston 5 of the silicone material and the piston 7 made of the silicone material, thereby obtaining a double-cavity mixer packaging device containing the freeze-dried shaped preparation.
使用时将一推杆 10装入活塞 7, 推动推杆 10向液体制剂腔 6方向运 动, 液体制剂腔 6内液体压力带动活塞 5向固体制剂腔 3方向运动; 当活 塞 5底部运动超过旁路 4下方时, 液体制剂腔 6内液体在活塞 7压力下, 通过旁路 4直接绕开活塞 5,进入固体制剂腔 3, 与其中的冻干赋形制剂混 合, 继续向前推动推杆至活塞 7顶部与活塞 5底部接触, 全部液体制剂腔
6内 1毫升去离子水完全与冻干赋形制剂混合,形成含有 3%三七总皂苷的 溶液; 打开出料盖 1, 继续推动推杆 10, 带动活塞 7紧压活塞 5, 将前述 的混合溶液通过出料嘴 2口服,形成保健食品。 实施例 5: In use, a push rod 10 is loaded into the piston 7, and the push rod 10 is pushed to move toward the liquid preparation chamber 6. The liquid pressure in the liquid preparation chamber 6 drives the piston 5 to move toward the solid preparation chamber 3; when the bottom of the piston 5 moves beyond the bypass 4 below, the liquid in the liquid preparation chamber 6 under the pressure of the piston 7, directly bypasses the piston 5 through the bypass 4, enters the solid preparation chamber 3, mixes with the freeze-dried shaped preparation, and continues to push the push rod to the piston forward. 7 top contact with the bottom of the piston 5, all liquid preparation chamber 1 ml of deionized water is completely mixed with the freeze-dried shaped preparation to form a solution containing 3% total saponins of Panax notoginseng; the discharge cover 1 is opened, the push rod 10 is continuously pushed, and the piston 7 is pressed to press the piston 5, the aforementioned The mixed solution is orally administered through the discharge nozzle 2 to form a health food. Example 5:
越橘提取物: 普鲁兰 =100mg:15mg, 配制成溶液, 灌注进入 0.5 毫升 成型模具, 冻干后装入塑料材质的双腔混料器的固体制剂腔 3, 然后将硅 胶材质的活塞 5装配入固体制剂腔 3底部、 旁路 4下方; 再将含有天然色 素的 20毫升去离子水灌装入硅胶材质的活塞 5隔离出的液体制剂腔 6; 之 后加入连有推杆 10的硅胶材质的活塞 7, 使液体完整保存于液体制剂腔 6 内, 不会从硅胶材质的活塞 5和硅胶材质的活塞 7之间渗出, 即得到包含 冻干赋形制剂的双腔混料器包装装置。 Bilberry extract: Pullulan = 100mg: 15mg, formulated into a solution, poured into a 0.5 ml molding die, lyophilized, filled into a solid cavity 3 of a plastic double-cavity mixer, and then a piston of silicone material 5 Assembled into the bottom of the solid preparation chamber 3, under the bypass 4; then 20 ml of deionized water containing natural pigment is filled into the liquid preparation chamber 6 separated by the piston 5 of the silica gel; then the silica gel with the push rod 10 is added. The piston 7 allows the liquid to be completely stored in the liquid preparation chamber 6, and does not ooze out between the silicone-made piston 5 and the silicone-made piston 7, thereby obtaining a double-cavity mixer packaging device containing the freeze-dried shaped preparation. .
使用时推动推杆 10向液体制剂腔 6方向运动,液体制剂腔 6内液体压 力带动活塞 5向固体制剂腔 3方向运动; 当活塞 5底部运动超过旁路 4下 方时, 液体制剂腔 6内液体在活塞 7压力下, 通过旁路 4直接绕开活塞 5, 进入固体制剂腔 3, 与其中的冻干赋形制剂混合, 继续向前推动推杆至活 塞 7顶部与活塞 5底部接触,全部液体制剂腔 6内 20毫升含有天然色素的 去离子水完全与冻干赋形制剂混合, 形成含有 0.5% 越橘提取物的溶液; 打开出料盖 1, 继续推动推杆 10, 带动活塞 7紧压活塞 5, 将前述的混合 溶液从出料嘴 2口服, 形成固体饮料食品。 When in use, the push rod 10 is pushed to move toward the liquid preparation chamber 6, and the liquid pressure in the liquid preparation chamber 6 drives the piston 5 to move toward the solid preparation chamber 3; when the bottom portion of the piston 5 moves below the bypass 4, the liquid in the liquid preparation chamber 6 Under the pressure of the piston 7, the piston 5 is directly bypassed by the bypass 4, enters the solid preparation chamber 3, mixes with the lyophilized shaped preparation therein, and continues to push the push rod forward until the top of the piston 7 contacts the bottom of the piston 5, all the liquid 20 ml of deionized water containing natural pigment in the preparation chamber 6 is completely mixed with the freeze-dried shaped preparation to form a solution containing 0.5% of cranberry extract; the discharge cover 1 is opened, the push rod 10 is continuously pushed, and the piston 7 is pressed. The piston 5, orally, the above-mentioned mixed solution is orally taken out from the discharge nozzle 2 to form a solid beverage food.
明的较佳实施例而已, 不能以此限定保护范围。 凡以本发明的权利要求范 围所述的简单的或等效的变化及修饰, 皆属于本发明的保护范围。
The preferred embodiment of the invention is not limited thereto. Simple or equivalent variations and modifications within the scope of the appended claims are intended to be included within the scope of the invention.
Claims
1.一种冻干赋型制剂的包装和递送系统, 包括冻干赋型制剂、 溶剂以 及包装和递送所述冻干赋型制剂和溶剂的包装和递送装置, 其特征在于, 所述包装和递送装置为双腔混料器, 其中溶剂以及冻干赋型制剂分别保存 于双腔混料器的不同腔体中, 通过双腔混料器各部件的相互作用使溶剂和 冻干赋型制剂在使用时可以即时混合并导出。 A packaging and delivery system for a lyophilized formulation comprising a lyophilized formulation, a solvent, and a package and delivery device for packaging and delivering the lyophilized formulation and solvent, characterized in that the package and The delivery device is a two-chamber mixer in which the solvent and the lyophilized formulation are separately stored in different chambers of the two-chamber mixer, and the solvent and the lyophilized formulation are made by the interaction of the components of the two-chamber mixer. It can be mixed and exported instantly when used.
2.如权利要求 1所述的冻干赋型制剂的包装和递送系统, 其特征在于, 所述冻干赋型制剂含有功效成分和粘结剂, 且粘结剂: 功效成分 =1:10 至 10: 1。 The packaging and delivery system for a freeze-dried formulation according to claim 1, wherein the lyophilized formulation contains an active ingredient and a binder, and the binder: efficacy component = 1:10 To 10: 1.
3.如权利要求 2所述的冻干赋型制剂的包装和递送系统, 其特征在于, 所述粘结剂是可食用、可做化妆品用或者可药用的一种水溶性高分子材料。 The packaging and delivery system for a freeze-dried formulation according to claim 2, wherein the binder is a water-soluble polymer material which is edible, cosmetic or pharmaceutically acceptable.
4.如权利要求 2所述的冻干赋型制剂的包装和递送系统, 其特征在于, 所述功效成分为化学药物、 生物药物、 中药提取物、 维生素、 矿物质、 化 妆有益成分以及其它对人体有益的活性成分中的一种或一种以上。 The packaging and delivery system for a freeze-dried formulation according to claim 2, wherein the functional ingredients are a chemical drug, a biopharmaceutical, a Chinese herbal extract, a vitamin, a mineral, a cosmetic benefit component, and the like. One or more of the active ingredients of the human body.
5.如权利要求 2-4任意一项所述的冻干赋型制剂的包装和递送系统, 其特征在于, 所述冻干赋型制剂还含有骨架支持剂、 增稠混悬剂、 抗氧化 剂、 矫味剂和香精、 透皮吸收促进剂、 pH调节剂中的一种或者一种以上。 The packaging and delivery system for a freeze-dried preparation according to any one of claims 2 to 4, wherein the freeze-dried preparation further comprises a skeleton support agent, a thickening suspension, and an antioxidant. One or more of a flavoring agent and a fragrance, a transdermal absorption enhancer, and a pH adjuster.
6.如权利要求 1所述的冻干赋型制剂的包装和递送系统, 其特征在于, 所述双腔混料器包括二腔体(3、 6 )、 二活塞(5、 7 )、 一旁路(4 )、 一推 杆按手 (10 )、 一出料器(2 )、 一出料盖 (1 )六部分。 6. The packaging and delivery system for a freeze-dried formulation according to claim 1, wherein the dual chamber mixer comprises two chambers (3, 6), two pistons (5, 7), a side Road (4), a push rod press hand (10), a discharge device (2), a discharge cover (1) six parts.
7.如权利要求 6所述的冻干赋型制剂的包装和递送系统, 其特征在于, 所述二腔体为固体制剂腔( 3 )和液体制剂腔( 6 ); 固体制剂腔( 3 ) 为靠 近出料器(2 )部分的腔体, 液体制剂腔(6 )为远离出料器(2 )部分的腔 体; 固体制剂腔(3 )及液体制剂腔(6 ) 为单个整体腔体通过活塞分隔成 的两个部分, 或由两个独立腔体连接在一起组成。 The packaging and delivery system for a freeze-dried preparation according to claim 6, wherein the two chambers are a solid preparation chamber (3) and a liquid preparation chamber (6); a solid preparation chamber (3) For the cavity near the portion of the discharger (2), the liquid preparation chamber (6) is a cavity away from the portion of the discharger (2); the solid preparation chamber (3) and the liquid preparation chamber (6) are a single integral cavity Two parts separated by a piston, or two independent cavities connected together.
8.如权利要求 7所述的一种冻干赋型制剂的包装和递送系统, 其特征 在于, 冻干赋型制剂 (9 )位于固体制剂腔(3 ) 中; 溶剂 (8 )位于液体制 剂腔(6 ) 中; 溶剂 (8 )选自水、 具有一定功效成分的营养液或精华液及 可与冻干赋型直接配合使用的其它各种溶剂。 8. A packaging and delivery system for a freeze-dried formulation according to claim 7, wherein the lyophilized formulation (9) is located in the solid formulation chamber (3); the solvent (8) is in the liquid formulation In the cavity (6); the solvent (8) is selected from the group consisting of water, nutrient solution or essence with certain functional ingredients, and various other solvents which can be directly used in combination with the freeze-dried form.
9.如权利要求 6-8任意一项所述的冻干赋型制剂的包装和递送系统,
其特征在于, 所述旁路(4)位于固体制剂腔侧面, 可使腔体中的溶剂通过 活塞运动至旁路处时形成开口从而与冻干赋型制剂进行混合; 所述推杆按 手(10)为向腔体施加压力以使活塞运动的装置; 所述出料器(2)为非注 射针头形式的任意形态的出料口; 所述出料盖 (1) 为可密封出料器(2) 口的装置, 使腔体内物质与外界环境隔离。 9. A packaging and delivery system for a freeze-dried formulation according to any of claims 6-8. The utility model is characterized in that the bypass (4) is located on the side of the solid preparation cavity, so that the solvent in the cavity can be opened when the piston moves to the bypass to form an opening to be mixed with the freeze-dried preparation; (10) means for applying pressure to the cavity to move the piston; the discharger (2) is a discharge port of any form in the form of a non-injection needle; the discharge cover (1) is a sealable discharge The device of the (2) port isolates the material in the cavity from the external environment.
10.如权利要求 1-9任意一项所述的冻干赋型制剂的包装和递送系统的 制备方法, 其特征在于, 包括以下步骤: 10. A method of preparing a package and delivery system for a freeze-dried formulation according to any of claims 1-9, comprising the steps of:
(a)将功效成分、 粘结剂及其它辅料配制成溶液、 乳浊液或者悬浮液 注模; 或将固体功效成分注模, 再加入粘结剂及其它辅料配成溶液、 乳浊 液或悬浮液; (a) Formulating functional ingredients, binders and other excipients into solutions, emulsions or suspensions; or molding solid functional ingredients, adding binders and other excipients to form solutions, emulsions or suspension;
(b )将(a)得到的溶液或悬浮液在定量成型模具中进行脱气; (b) degassing the solution or suspension obtained in (a) in a quantitative molding die;
(c)将(b )得到的脱气后的溶液、 乳浊液或悬浮液或直接将(a)得 到的溶液乳浊液或悬浮液、 在低温下冷冻; (c) the degassed solution, emulsion or suspension obtained in (b) or directly the emulsion or suspension of the solution obtained in (a), frozen at low temperature;
( d )将(c)得到的制剂在定量成型模具中冷冻干燥、 除去溶剂, 得 到冻干赋型制剂; (d) lyophilizing the preparation obtained in (c) in a quantitative molding die, removing the solvent, and obtaining a lyophilized formulation;
(e)将(d)得到的冻干赋型制剂脱离成型模具并装入包装装置或其 成型模具就是其中一个腔体, 以此直接进行装配。
(e) The lyophilized formulation obtained in (d) is taken out of the molding die and loaded into a packaging device or a molding die thereof, which is one of the cavities, thereby directly assembling.
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US11452693B2 (en) | 2017-07-12 | 2022-09-27 | Conopco, Inc. | Freeze dried active composition and a system for using the same |
US11730685B2 (en) | 2017-07-12 | 2023-08-22 | Conopco, Inc. | Skin composition booster oil |
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CN103318551A (en) * | 2013-06-24 | 2013-09-25 | 李和伟 | System for packaging and delivering freeze-dried excipient and preparation method of freeze-dried excipient |
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