WO2022052672A1 - 一种泡腾凝胶干粉制剂及其制备方法 - Google Patents

一种泡腾凝胶干粉制剂及其制备方法 Download PDF

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WO2022052672A1
WO2022052672A1 PCT/CN2021/110337 CN2021110337W WO2022052672A1 WO 2022052672 A1 WO2022052672 A1 WO 2022052672A1 CN 2021110337 W CN2021110337 W CN 2021110337W WO 2022052672 A1 WO2022052672 A1 WO 2022052672A1
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dry powder
effervescent
gel
agent
gel dry
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PCT/CN2021/110337
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English (en)
French (fr)
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张秋野
王岩松
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宁波聚焦生物医药科技股份有限公司
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Priority to US18/007,043 priority Critical patent/US20230277440A1/en
Publication of WO2022052672A1 publication Critical patent/WO2022052672A1/zh

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/40—Effervescence-generating compositions
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/14—Yeasts or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/11—Lactobacillus
    • A23V2400/113—Acidophilus
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/11—Lactobacillus
    • A23V2400/175—Rhamnosus
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/51—Bifidobacterium

Definitions

  • the invention relates to an oral preparation for medicine, food and health care products, in particular to an effervescent gel dry powder preparation and a preparation method thereof.
  • Oral preparations generally include tablets, capsules, suspensions, granules, solutions, syrups, gels, and the like.
  • Oral preparations generally include tablets, capsules, suspensions, granules, solutions, syrups, gels, and the like.
  • the swallowing reflex is impaired, and during the swallowing process, aspiration is easy to occur, oral liquid or solid. Inhaled into the trachea, resulting in aspiration pneumonia or suffocation or even death. Therefore, the most suitable oral dosage form for them is a gel with a certain viscosity and the viscosity can be adjusted.
  • a certain viscosity can make the gel adhere to the mucous membranes of the oral cavity and pharynx, and can only enter the esophagus by swallowing, and prevent aspiration into the trachea; a certain consistency can make the gel form larger blocks and reduce its fluidity. It is easy to swallow and prevents oral substances from flowing into the trachea due to postural gravity.
  • the technical problem to be solved by the present invention is to provide a novel oral effervescent gel preparation with adjustable viscosity. It can meet the needs of infants and young children and some patients with special swallowing reflex dysfunction for oral drugs and food.
  • the present invention provides an effervescent gel dry powder preparation
  • the effervescent gel dry powder preparation comprises a pharmaceutical ingredient or one of the active ingredients, fast-expanding gel particles, a foaming agent and an auxiliary filler;
  • the fast-swelling gel particles are composed of carbomer or polycarbomer non-uniformly adhered to the surface of the ethylene glycol particles;
  • the weight percentage of the fast-swelling gel particles in the effervescent gel dry powder preparation is 5% to 15%;
  • the weight percentage of the foaming agent in the effervescent gel dry powder formulation is not less than 1/5 of the weight percentage of the fast-expanding gel particles in the effervescent gel dry powder formulation.
  • the pharmaceutical ingredients are cephalosporins, macrolides, ribavirin, oseltamivir, fumarate, ibuprofen, acetaminophen, vitamins, Dextromethorphan hydrobromide or Chinese patent medicine granules.
  • the weight percentage of the pharmaceutical ingredient in the effervescent gel dry powder formulation is 1% to 50%.
  • the active ingredient is Lactobacillus acidophilus, AKK, Bifidobacterium, Lactobacillus rhamnosus, Clostridium butyricum, Saccharomyces boulardii, Enterococcus, Bacillus licheniformis or Bacillus cereus.
  • the fast-expanding gel particle card is Bomer 971P uniformly adhered to the surface of polyethylene glycol 6000 wax particles to form relatively dense particle substances.
  • the foaming agent is sodium bicarbonate, and the weight percentage of the foaming agent in the effervescent gel dry powder formulation is 1% to 5%.
  • the auxiliary filler includes a flavoring agent, a taste-masking agent and a coloring agent, and the flavoring agent accounts for 40%-90% by weight of the effervescent gel dry powder formulation; the taste-masking agent
  • the weight percentage of the colorant in the effervescent gel dry powder preparation is 0% to 10%; the weight percentage of the colorant in the effervescent gel dry powder preparation is 0% to 6%.
  • Another aspect of the present invention is to provide an effervescent gel dry powder preconditioning, which is used for mixing with other granular preparations to form an effervescent gel preparation.
  • the dry gel powder preconditioning includes fast-swelling gel particles and a foaming agent, and the weight percentage of the foaming agent in the dry effervescent gel preconditioning is not less than the percentage by weight of the fast-swelling gel particles in the effervescent gel. 1/5 of the weight percentage of the dry powder pre-conditioning agent; the fast-swelling gel particle card is Bomer 971P uniformly adhered to the surface of the polyethylene glycol 6000 wax particles to form a denser particle material; the foaming agent adopts hydrogen carbonate sodium.
  • the fast-swelling gel particle card used in the present invention is Bomer 971P uniformly adhered to the surface of polyethylene glycol 6000 wax particles to form relatively dense particles, and its average particle size is 50-250 ⁇ m.
  • a large number of carboxyl groups carried by poly or carbomer will react with sodium bicarbonate in sodium bicarbonate solution to produce water and carbon dioxide gas, while carbomer will become thick and form gel in alkaline solution. Therefore, the mixture of the fast-expanding gel particles and the foaming agent of the present invention can quickly form a bubble gel after being mixed with water, and simultaneously entrain the drug or active substance.
  • the invention of the present invention lies in the following aspects:
  • the present invention proposes to use the method that quick-swelling gel particles and foaming agent are matched to produce foam-containing gel, thereby producing a kind of novel oral preparation type—effervescent gel, which improves the gel in the prior art. Mouthfeel and smoothness of the formulation.
  • the usage content of the fast-swelling gel particles is further determined through experiments, so as to obtain the best taste and smoothness of the gel preparation. At the same time, the use ratio between the fast-swelling gel particles and the foaming agent was determined.
  • Figure 1 is a schematic diagram of the particle size distribution of the fast-swelling gel particles used in the present invention.
  • Fig. 2 is a schematic diagram showing the comparison of the dissolution rate of the bubble gel produced by the present invention and the Cefaclor dry suspension formulation in the prior art.
  • the material is poured out, and after a little cooling, it is passed through a 20-mesh sieve, that is, the preparation of the fast-swelling gelling agent granules is completed.
  • the average particle size of the fast-swelling gel particles is about 150 ⁇ m.
  • the particle size distribution of the fast-swelling gel particles is shown in Figure 1.
  • Cefaclor Foaming agent sodium bicarbonate flavoring agent Cane sugar powder taste masking agent fruity essence Colorant sunset yellow
  • the fast-swelling gelling agent particles are prepared, and the preparation process of the fast-swelling gelling agent particles is completely consistent with the preparation process of the fast-swelling gelling agent particles described in Example 1.
  • the fast-swelling gelling agent particles are prepared, and the preparation process of the fast-swelling gelling agent particles is completely consistent with the preparation process of the fast-swelling gelling agent particles described in Example 1.
  • the fast-swelling gelling agent particles are prepared, and the preparation process of the fast-swelling gelling agent particles is completely consistent with the preparation process of the fast-swelling gelling agent particles described in Example 1.
  • the fast-swelling gelling agent particles are prepared, and the preparation process of the fast-swelling gelling agent particles is completely consistent with the preparation process of the fast-swelling gelling agent particles described in Example 1.
  • Cefaclor Foaming agent sodium bicarbonate flavoring agent Cane sugar powder taste masking agent fruity essence Colorant sunset yellow
  • the fast-swelling gelling agent particles are prepared, and the preparation process of the fast-swelling gelling agent particles is completely consistent with the preparation process of the fast-swelling gelling agent particles described in Example 1.
  • the fast-swelling gelling agent particles are first prepared, and the preparation process of the fast-swelling gelling agent particles is completely consistent with the preparation process of the fast-swelling gelling agent particles described in Example 1.
  • Cefaclor Foaming agent sodium bicarbonate flavoring agent Cane sugar powder taste masking agent fruity essence Colorant sunset yellow
  • the weight percentage content of the fast-swelling gel particles in the present invention needs to be set between 5% and 15%, so as to ensure that the prepared effervescent gel dry powder formulation is mixed with water. It has a suitable viscosity, so that patients with dysphagia can easily perform oral actions.
  • the weight percentage of the foaming agent should be greater than 1/5 of the weight percentage of the effervescent gel dry powder, so as to ensure that the effervescent gel dry powder preparation forms a uniform gel after mixing with water formulation to prevent flocculation from appearing.
  • Figure 2 The results of the dissolution comparison between the bubble gel of the present invention and the Cefaclor dry suspension preparation in the existing market are shown in Figure 2. It can be seen that the bubble gel of the present invention is released in vitro. Similar to Shiclau Dry Suspension, almost complete release can be achieved within 30 minutes, with no significant difference.
  • This example is to make a kind of bubble gel dry powder pre-conditioning agent.
  • the fast-swelling gelling agent particles are prepared.
  • the preparation process of the glue particles is completely the same.
  • the bubble gel dry powder preparation or the bubble gel dry powder preconditioning provided by the present invention can rapidly form a gel preparation suitable for oral administration by patients with dysphagia.
  • the invention of the present invention is mainly in two aspects.
  • the present invention proposes a method for producing a foam-containing gel by using a method in which fast-swelling gel particles are combined with a foaming agent.
  • carbomer or polymer A large number of carboxyl groups carried by carbophil will react with sodium bicarbonate in sodium bicarbonate solution to produce water and carbon dioxide gas, thereby improving the taste and smoothness of the gel preparation in the prior art.
  • the usage content of the fast-swelling gel particles and the usage ratio between the fast-swelling gel particles and the foaming agent are further determined through experiments, so as to obtain the best taste and smoothness of the gel preparation.

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Abstract

一种泡腾凝胶(Effervescent gel EG)剂。其主要由速膨凝胶剂，致泡剂，活性成分，辅助成分所组成。泡腾凝胶剂与适量的水剂，或水溶液混合，可快速(一般少于30秒)膨胀并形成均匀多泡水凝胶。

Description

一种泡腾凝胶干粉制剂及其制备方法 技术领域
本发明涉及一种用于药物、食品及保健品的口服制剂，具体涉及一种泡腾凝胶干粉制剂及其制备方法。
背景技术
口服制剂一般包括片剂、胶囊剂、混悬剂、颗粒剂、溶液剂、糖浆剂和凝胶剂等。对于婴幼儿及一些具有特殊吞咽反射功能障碍的患者，由于他(她)们因为年龄,身体或患病原因，吞咽反射出现障碍，在吞咽过程中，很容易出现误吸，将液体或固体口服物吸入气管，造成吸入性肺炎或窒息甚至死亡。因此，最适合他(她)们的口服剂型是具有一定黏稠度，且黏稠度可调节的凝胶剂。一定的黏度可以使凝胶剂黏附于口腔和咽部粘膜，只能通过吞咽进入食管，而防止误吸进入气管；一定的稠度可以使凝胶剂形成较大块状，降低其流动性，既易于吞咽，又能防止口服物质因体位重力原因流入气管。
根据患者吞咽反射功能障碍的严重程度不同，饮食习惯的不同，患者需要不同黏稠度的凝胶剂去满足各种不同的需求。目前市场上的凝胶剂很少，黏稠度是固定的，不可调节，制备过程中一般需要加入防腐剂，且需低温保存。
由于目前市场凝胶剂的缺陷，远远不能满足婴幼儿及一些具有特殊吞咽反射功能障碍的患者的需求，且目前的凝胶剂不是新鲜配制，口感较差，也不容易获得广泛应用。
发明内容
本发明所要解决的技术问题是提供一种具有黏稠度可调的新型口服泡腾凝胶制剂。可以满足婴幼儿及一些具有特殊吞咽反射功能障碍的患者对口服药品及食品的需求。
为实现上述技术效果，本发明提供一种泡腾凝胶干粉制剂，所述泡腾凝胶干粉制剂包含药物成分或活性成分之一、速膨凝胶颗粒、致泡剂和辅助填料；所述速膨凝胶颗粒由卡波姆或聚卡波非均匀粘附聚于乙二醇颗粒表面构成；所述泡腾凝胶干粉制剂中速膨凝胶颗粒的重量百分比为5％～15％；且所述致泡剂占所述泡腾凝胶干粉制剂的重量百分比不小于所述速膨凝胶颗粒占所述泡腾凝胶干粉制剂的重量百分比的1/5。
在一个实施例中，所述药物成分是头孢类药物、大环内酯类药物、利巴韦林、奥司他韦、富马酸亚、布洛芬、对乙酰氨基酚、维生素类药物、氢溴酸右美沙芬或中成药颗粒。
在一个实施例中，所述药物成分占所述泡腾凝胶干粉制剂的重量百分比为1％～50％。
在一个实施例中，所述活性成分为嗜酸乳杆菌、AKK、双歧杆菌、鼠李糖乳杆菌、酪酸梭菌、布拉酵母菌、肠球菌、地衣芽孢杆菌或蜡样芽孢杆菌。
在一个实施例中，所述速膨凝胶颗粒卡为波姆971P均匀粘附于聚乙二醇6000蜡粒表面形成较致密的颗粒物质。
在一个实施例中，所述致泡剂采用碳酸氢钠，所述致泡剂占所述泡腾凝胶干粉制剂的重量百分比为1％～5％。
在一个实施例中，所述辅助填料包括矫味剂、掩味剂和着色剂，所述矫味剂占所述泡腾凝胶干粉制剂的重量百分比为40％～90％；所述掩味剂占所述泡腾凝胶干粉制剂的重量百分比为0％～10％；所述着色剂占所述泡腾凝胶干粉制剂的重量百分比为0％～6％。
本发明的另一个方面还在于提供一种泡腾凝胶干粉预调剂，所述泡腾凝胶干粉预调剂用于与其他颗粒制剂混合配置成泡腾凝胶制剂，所述所述泡腾凝胶干粉预调剂包括速膨凝胶颗粒和致泡剂，且所述致泡剂占所述泡腾凝胶干粉预调剂的重量百分比不小于所述速膨凝胶颗粒占所述泡腾凝胶干粉预调剂的重量百分比的1/5；所述速膨凝胶颗粒卡为波姆971P均匀粘附于聚乙二醇6000蜡粒表面形成较致密的颗粒物质；所述致泡剂采用碳酸氢钠。
本发明中所使用的所述速膨凝胶颗粒卡为波姆971P均匀粘附于聚乙二醇6000蜡粒表面形成较致密的颗粒物质，其平均粒径为50-250μm，由于卡波姆聚 或卡波非自身所带的大量羧基，其在碳酸氢钠溶液中会与碳酸氢钠发生反应生产水和二氧化碳气体，同时卡波姆在碱性溶液中会变得浓稠形成凝胶。因此本发明的速膨凝胶颗粒和致泡剂混合物在与水混合后能够快速的形成气泡凝胶，同时把药物或活性物质裹挟在内。
本发明的发明点在于如下几个方面：
1.本发明提出了使用速膨凝胶颗粒与致泡剂相配合的方法生产含泡凝胶，从而产生了一种新型口服制剂类型—泡腾凝胶剂，改善了现有技术中凝胶制剂的口感和顺滑度。
2.本发明中进一步通过实验确定了速膨凝胶颗粒的使用含量，以获得最佳的凝胶制剂的口感和顺滑度。同时确定了速膨凝胶颗粒与致泡剂之间的使用比例。
附图说明
附图用来提供对本发明的进一步理解，并且构成说明书的一部分，与本发明的实施例共同用于解释本发明，并不构成对本发明的限制。在附图中：
图1为本发明中所使用的速膨凝胶颗粒的粒径分布示意图。
图2为本发明所生成的气泡凝胶与现有技术中的希克劳干混悬制剂在头孢克洛成分上的溶出度对比示意图。
具体实施方式
以下结合附图对本发明实施方式做进一步阐述。
实施例1
以上所述，仅为本发明的具体实施案例，本发明的保护范围并不局限于此，任何熟悉本技术的技术人员在本发明所述的技术规范内，对本发明的修改或替换，都应在本发明的保护范围之内。
本实施例中首先制备速膨凝胶剂颗粒，所述速膨凝胶剂颗粒的制作过程如下：
将500克卡波姆971P置于一湿法制粒机锅内，通过锅的夹层用95度水浴加热卡波姆971P。在15转/分钟的搅拌桨搅拌下，卡波姆971P将逐渐升温，当温度达到85-90度时，将聚乙二醇6000(PEG6000)颗粒320克缓慢倒入湿法制粒机锅内，然后将搅拌桨速度提高为30转/分钟，保持95度水浴加热。大约2-10 分钟后，卡波姆将均匀粘附于聚乙二醇6000蜡粒表面，形成较致密的颗粒。制粒完成后将物料倒出，稍冷却后过20目筛，即速膨凝胶剂颗粒为制备完成。速膨凝胶剂颗粒平均粒径约为150μm。速膨凝胶剂颗粒的粒径分布见图1。
取上述制备完成的速膨凝胶颗粒10g、药物活性成分6g、致泡剂2g、矫味剂84g、掩味剂3g、着色剂1g。充分混合制成100g本实施例的泡腾凝胶干粉制剂。本实施例中所使用的药物活性成分、致泡剂、矫味剂、掩味剂和着色剂的具体使用的化合物如下表1所示。
表1
成分 具体化合物
药物活性成分 头孢克洛
致泡剂 碳酸氢钠
矫味剂 蔗糖粉
掩味剂 果味香精
着色剂 落日黄
实施例2
本实施例中首先制备速膨凝胶剂颗粒，所述速膨凝胶剂颗粒的制作过程与实施例1中的所记载的速膨凝胶剂颗粒制备过程完全一致。
取上述制备完成的速膨凝胶颗粒10g、药物活性成分10g、致泡剂3g、矫味剂73g、掩味剂3g、着色剂1g。充分混合制成100g本实施例的泡腾凝胶干粉制剂。本实施例中所使用的药物活性成分、致泡剂、矫味剂、掩味剂和着色剂的具体使用的化合物如下表2所示。
表2
成分 具体化合物
药物活性成分 头孢克洛
致泡剂 碳酸氢钠
矫味剂 木糖醇
掩味剂 果味香精
着色剂 落日黄
实施例3
本实施例中首先制备速膨凝胶剂颗粒，所述速膨凝胶剂颗粒的制作过程与实施例1中的所记载的速膨凝胶剂颗粒制备过程完全一致。
取上述制备完成的速膨凝胶颗粒12g、药物活性成分8g、致泡剂4g、矫味剂72g、掩味剂3g、着色剂1g。充分混合制成100g本实施例的泡腾凝胶干粉制剂。本实施例中所使用的药物活性成分、致泡剂、矫味剂、掩味剂和着色剂的具体使用的化合物如下表3所示。
表3
成分 具体化合物
药物活性成分 头孢克洛
致泡剂 碳酸氢钠
矫味剂 木糖醇
掩味剂 果味香精
着色剂 落日黄
实施例4
本实施例中首先制备速膨凝胶剂颗粒，所述速膨凝胶剂颗粒的制作过程与实施例1中的所记载的速膨凝胶剂颗粒制备过程完全一致。
取上述制备完成的速膨凝胶颗粒15g、药物活性成分12g、致泡剂4g、矫味剂58g、掩味剂8g、着色剂1g。充分混合制成100g本实施例的泡腾凝胶干粉制剂。本实施例中所使用的药物活性成分、致泡剂、矫味剂、掩味剂和着色剂的具体使用的化合物如下表4所示。
表4
成分 具体化合物
药物活性成分 头孢克洛
致泡剂 碳酸氢钠
矫味剂 蔗糖粉
掩味剂 果味香精
着色剂 落日黄
比较例1
本实施例中首先制备速膨凝胶剂颗粒，所述速膨凝胶剂颗粒的制作过程与实施例1中的所记载的速膨凝胶剂颗粒制备过程完全一致。
取上述制备完成的速膨凝胶颗粒4g、药物活性成分10g、致泡剂2g、矫味剂80g、掩味剂3g、着色剂1g。充分混合制成100g本实施例的泡腾凝胶干粉制剂。本实施例中所使用的药物活性成分、致泡剂、矫味剂、掩味剂和着色剂的具体使用的化合物如下表5所示。
表5
成分 具体化合物
药物活性成分 头孢克洛
致泡剂 碳酸氢钠
矫味剂 蔗糖粉
掩味剂 果味香精
着色剂 落日黄
比较例2
本实施例中首先制备速膨凝胶剂颗粒，所述速膨凝胶剂颗粒的制作过程与实施例1中的所记载的速膨凝胶剂颗粒制备过程完全一致。
取上述制备完成的速膨凝胶颗粒18g、药物活性成分6g、致泡剂8g、矫味剂64g、掩味剂3g、着色剂1g。充分混合制成100g本实施例的泡腾凝胶干粉制剂。本实施例中所使用的药物活性成分、致泡剂、矫味剂、掩味剂和着色剂的具体使用的化合物如下表5所示。
表5
成分 具体化合物
药物活性成分 头孢克洛
致泡剂 碳酸氢钠
矫味剂 蔗糖粉
掩味剂 果味香精
着色剂 落日黄
比较例3
本实施例中首先制备速膨凝胶剂颗粒，所述速膨凝胶剂颗粒的制作过程与实施例1中的所记载的速膨凝胶剂颗粒制备过程完全一致。
取上述制备完成的速膨凝胶颗粒13g、药物活性成分6g、致泡剂2g、矫味剂75g、掩味剂3g、着色剂1g。充分混合制成100g本实施例的泡腾凝胶干粉制剂。本实施例中所使用的药物活性成分、致泡剂、矫味剂、掩味剂和着色剂的具体使用的化合物如下表5所示。
表5
成分 具体化合物
药物活性成分 头孢克洛
致泡剂 碳酸氢钠
矫味剂 蔗糖粉
掩味剂 果味香精
着色剂 落日黄
将上述制备完成的泡腾凝胶干粉制取10g剂置于干净容器内，混合均匀后，加入25毫升水，用小汤勺轻轻搅拌约10-20秒钟，泡腾凝胶干粉制剂与水混合后，迅速膨胀，形成均一的泡腾凝胶，上述实施例1-4及比较例1-3所形成的凝胶其口感效果如下表6所示。
表6
实例 顺滑度 粘稠度
实施例1 优 优
实施例2 优 优
实施例3 优 优
实施例4 优 优
比较例1 优 过稀
比较例2 优 过稠
比较例3 絮状块 优
具有吞咽障碍的病人其在食用流食时，当食物过稀时容易造成呛咳；当食物过稠时容易引起吞咽困难。同时为了使药物或活性物质充分溶解在水中，所使用的水的用量是存在最低限用量的。根据表6可知，本发明中速膨凝胶颗粒的重量百分比含量需设定在5％～15％之间，从而保证所制备的泡腾凝胶干粉制剂在与水混合后所获得的凝胶具有合适的粘稠度，从而使得吞咽障碍病人能够较为容易的进行口服动作。同时为了避免凝胶中形成絮状结块，致泡剂的重量百分比应大于泡腾凝胶干粉重量百分比的1/5，从而保证泡腾凝胶干粉制剂在与水混合后形成均匀的凝胶制剂，防止絮状结块出现。本发明的气泡凝胶与现有市场中的希克劳干混悬制剂在头孢克洛成分上的溶出度对比结果如图2所示，可以看出本发明的气泡凝胶在药物体外释放上和希克劳干混悬剂类似，30分钟均可达到基本完全释放，没有显著差异。
实施例5
本实施例在于制作一种气泡凝胶干粉预调剂，本实施例中首先制备速膨凝胶剂颗粒，所述速膨凝胶剂颗粒的制作过程与实施例1中的所记载的速膨凝胶剂颗粒制备过程完全一致。
取上述制备完成的速膨凝胶颗粒100g与碳酸氢钠20g充分混合制成120g本实施例的气泡凝胶干粉预调剂。取上述2g气泡凝胶干粉预调剂置于干净容器内，然后加入药物混合均匀后，加入25毫升水，用小汤勺轻轻搅拌约15-20秒钟，泡腾凝胶干粉制剂与水混合后，迅速膨胀，形成均一的泡腾凝胶。混合后所获得的凝胶具有合适的粘稠度，从而使得吞咽障碍病人能够较为容易的进行口服动作。
由上述实施例可知，本发明所提供的气泡凝胶干粉制剂或气泡凝胶干粉预调 剂能够实现快速形成适合于使具有吞咽障碍病人较为容易的进行口服的凝胶制剂，本实施例中所体现本发明的发明点主要在两个方面，第一、本发明提出了使用速膨凝胶颗粒与致泡剂相配合的方法生产含泡凝胶的方法，本发明中利用，卡波姆或聚卡波非自身所带的大量羧基，其在碳酸氢钠溶液中会与碳酸氢钠发生反应生产水和二氧化碳气体，从而改善了现有技术中凝胶制剂的口感和顺滑度。第二、本发明中进一步通过实验确定了速膨凝胶颗粒的使用含量以及速膨凝胶颗粒与致泡剂之间的使用比例，以获得最佳的凝胶制剂的口感和顺滑度。

Claims (8)

  1. 一种泡腾凝胶干粉制剂，其特征在于，所述泡腾凝胶干粉制剂包含药物成分或活性成分之一、速膨凝胶颗粒、致泡剂和辅助填料；所述速膨凝胶颗粒由卡波姆或聚卡波非均匀粘附与聚乙二醇颗粒表面构成；所述泡腾凝胶干粉制剂中速膨凝胶颗粒的重量百分比为5％～15％；且所述致泡剂占所述泡腾凝胶干粉制剂的重量百分比不小于所述速膨凝胶颗粒占所述泡腾凝胶干粉制剂的重量百分比的1/5。
  2. 根据权利要求1所述的泡腾凝胶干粉制剂，其特征在于，所述药物成分是头孢类药物、大环内酯类药物、利巴韦林、奥司他韦、富马酸亚铁、布洛芬、对乙酰氨基酚、维生素类药物、氢溴酸右美沙芬或中成药颗粒。
  3. 根据权利要求1所述的泡腾凝胶干粉制剂，其特征在于，所述活性成分为植物乳杆菌、嗜酸乳杆菌、AKK、双歧杆菌、鼠李糖乳杆菌、酪酸梭菌、布拉酵母菌、肠球菌、地衣芽孢杆菌或蜡样芽孢杆菌。
  4. 根据权利要求1所述的泡腾凝胶干粉制剂，其特征在于，所述药物成分占所述泡腾凝胶干粉制剂的重量百分比为1％～50％。
  5. 根据权利要求1所述的泡腾凝胶干粉制剂，其特征在于，所述速膨凝胶颗粒为卡波姆971P，卡波姆974P，卡波姆934P或聚卡波非均匀粘附于聚乙二醇蜡粒表面，形成较致密的颗粒物质，所述聚乙二醇为聚乙二醇4000，聚乙二醇6000，聚乙二醇8000，聚乙二醇10000或聚乙二醇12000.
  6. 根据权利要求1所述的泡腾凝胶干粉制剂，其特征在于，所述致泡剂采用碳酸氢钠，所述致泡剂占所述泡腾凝胶干粉制剂的重量百分比为1％～5％。
  7. 根据权利要求1所述的泡腾凝胶干粉制剂，其特征在于，所述辅助填料包括矫味剂、掩味剂和着色剂，所述矫味剂占所述泡腾凝胶干粉制剂的重量百分比为40％～90％；所述掩味剂占所述泡腾凝胶干粉制剂的重量百分比为0％～10％；所述着色剂占所述泡腾凝胶干粉制剂的重量百分比为0％～6％。
  8. 一种泡腾凝胶干粉预调剂，其特征在于，所述泡腾凝胶干粉预调剂用于与其他颗粒制剂混合配置成泡腾凝胶制剂，所述所述泡腾凝胶干粉预调剂包括速膨 凝胶颗粒和致泡剂，且所述致泡剂占所述泡腾凝胶干粉预调剂的重量百分比不小于所述速膨凝胶颗粒占所述泡腾凝胶干粉预调剂的重量百分比的1/5；所述速膨凝胶颗粒卡为波姆971P均匀粘附于聚乙二醇6000蜡粒表面形成较致密的颗粒物质；所述致泡剂采用碳酸氢钠或碳酸氢钾。
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