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WO2017035747A1 - Capsules à pression positive et procédé pour les fabriquer - Google Patents

Capsules à pression positive et procédé pour les fabriquer Download PDF

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Publication number
WO2017035747A1
WO2017035747A1 PCT/CN2015/088634 CN2015088634W WO2017035747A1 WO 2017035747 A1 WO2017035747 A1 WO 2017035747A1 CN 2015088634 W CN2015088634 W CN 2015088634W WO 2017035747 A1 WO2017035747 A1 WO 2017035747A1
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WO
WIPO (PCT)
Prior art keywords
capsule
positive pressure
recited
gelatin
pressure
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2015/088634
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English (en)
Inventor
Garry Tsaur
Ting-Hua Wang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
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Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to PCT/CN2015/088634 priority Critical patent/WO2017035747A1/fr
Publication of WO2017035747A1 publication Critical patent/WO2017035747A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/485—Inorganic compounds
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A61K9/4825—Proteins, e.g. gelatin
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4833—Encapsulating processes; Filling of capsules

Definitions

  • the present invention relates to a positive pressure capsule and method of manufacturing of said capsule, the capsule can accelerate the destruction of the capsule and form an opening and help quick release of drug.
  • Said capsule is characterized with a sealed capsule containing a gas and the internal pressure of the capsule is maintained at a positive pressure.
  • Capsule is a fast developing pharmaceutical dosage form and 0.1 ⁇ 0.7 mm capsules are widely used in oral drugs and health foods with the advantages of easy storage, accurate dose and controllable drug release; moreover, capsule can mask the odor of the active ingredients of drugs and maintain drug activity and therefore are easier for the users to accept.
  • the dosage forms of capsules allow storage of drugs inside capsules and the sealing characteristic of capsules helps prevent reduced drug activity and keep moisture away from the contained drug by avoiding direct contact of the contained drug contact with outside air and water and as a result helps maintain long-term stability.
  • Some pharmacologically active substances may be difficult to be formulated into commercially acceptable formulations due to their biopharmaceutical or physico-chemical properties.
  • such substances may be administered in the form of a liquid carrier medium and the solvents 1, 2-propanediol as well as dimethylisosorbide both have great potential to be used as a liquid carrier medium.
  • the composition of carrier media allows formation of an emulsion in the stomach, thereby facilitating the absorption of the pharmaceutically active substance.
  • a carrier medium must be accurately prepared, so that it does not affect the pharmaceutical composition and does not destroy its beneficial properties. Solubilizing properties of the drug carrier may change the nature of the active substance and lead to precipitation, resulting in insufficient dose in patients.
  • the emulsifying properties of pharmaceutical carriers may vary and may not form an emulsion in the stomach upon administration and a pharmaceutically active substance will not be absorbed properly.
  • liquid formulations encapsulated in the capsule provide a very convenient method for administration of such pharmaceutically active substances.
  • commercially acceptable liquid-filling capsules are also accompanied by difficulties in limitations on applications.
  • Capsules used in pharmaceutical products can be divided into hard capsules and soft capsules, including hard capsules (hereinafter referred to as hard capsules) which can be filled with powder or fine particles of solid pharmaceutical drugs and soft capsules (hereinafter referred to as soft capsules) which can be filled other liquid drugs.
  • hard capsules hereinafter referred to as hard capsules
  • soft capsules which can be filled other liquid drugs.
  • the raw materials of capsules can be gelatin, sorbitol, hydroxypropyl methylcellulose (HPMC) and opaque food coloring or other additives.
  • HPMC hydroxypropyl methylcellulose
  • gelatin is a protein or peptide extracted from animal skin, bone, or connective tissues and contains collagen and a hydrophilic layer of pale yellow protein layer is obtained after boiling in the water, namely gelatin.
  • HPMC hydroxypropyl methylcellulose
  • HPMC hydroxypropyl methylcellulose
  • the alkoxy anion produced by hydroxy deprotonation of cellulose can act on propylene oxide and generate hydroxypropyl cellulose ether as well as be condensed with methyl chloride to form methyl cellulose ether.
  • hydroxypropyl methyl cellulose will be produced if both reactions occur simultaneously.
  • seaweed extracts i.e. polysaccharide hydrocolloid as an alternative raw material.
  • Plant materials help prevent cross-linking reaction with proteins of animal source and maintain the strength of the capsule body.
  • improvement of the raw materials of soft capsules has been taken seriously in recent years.
  • the market share of other alternative raw materials such as agarose, soluble starch ester derivatives, HPMC or carragheenin, also has increased gradually over the years.
  • One of the purposes of improvement of capsules is to enhance the bioavailability of pharmaceutical agents.
  • the active ingredient can be released quickly in the form of a liquid when the capsule ruptures. And different from lozenge composition, complete disintegration of the capsule is not necessary to make the active ingredient become absorbable. Meanwhile, dispersion of the insoluble active ingredients in liquid carriers provides faster absorption, e.g. a solution of a hydrophobic drug in a hydrophilic solvent; while the capsule will be broken in the stomach during the process of digestion and hydrophobic drugs may be dispersed in gastric juice.
  • the solutions include: 1. addition of antioxidants, 2 adjustment capsule formula and change its composition, such as the ratio of water and elasticizer, 3 uses materials that are less easily oxidized.
  • present invention provides a positive capsule which takes advantage of the internal positive pressure of the capsule and accelerates destruction and disintegration of the capsule in the stomach after administration and subsequently accelerates release of the drug so as to facilitate drug absorption by organisms.
  • the capsule is a sealed seamless capsule.
  • the internal pressure of the capsule must be a positive pressure and is higher than one atmosphere pressure.
  • the capsule contains a gas and the gas is oxygen, helium, nitrogen, or carbon dioxide or a mixture of the abovementioned gases.
  • the raw material of the capsule is gelatin, that is, animal source hydrolyzed collagen.
  • the raw material of the capsule is hydroxypropyl methylcellulose (HPMC) .
  • the capsule material may further include agar, starch, alginic acid, guar gum, and a pharmaceutically acceptable sunscreen, plasticizer and the like.
  • the gelatin is alkali-treated gelatin, acid-treated gelatin, or chemically modified gelatin.
  • the plasticizer is selected from the following groups: glycerin, sorbitol, maltose, glucose, polysaccharides, sucrose, xylitol, mannitol, propylene glycol, polyethylene glycol.
  • the sunscreen agent is selected from the following groups: caramel, titanium oxide, iron oxide.
  • the filling of the capsule is liquid, suspension, paste, powder, granule and the like.
  • the present invention provides a method for producing positive pressure capsules, wherein the capsules are filled under positive pressure environment followed by sealing the capsule while the bubbles in the capsule are retained and such capsule product is a positive pressure capsule under the environment of 1 atm.
  • the present invention also provides another method for producing positive pressure capsules, wherein the capsules are filled at low temperature and the temperature is below 25°C followed by sealing the capsule while a bubble is retained inside the capsule and such capsule product is a positive pressure capsule at room temperature.
  • Fig. 1 is the schematic diagram of the positive pressure capsule of the invention.
  • Fig. 2 is another schematic diagram of the positive pressure capsule of the invention.
  • Fig. 3A is the schematic diagram of the positive pressure capsule of the invention in the stomach before been digested after administration.
  • Fig. 3B is the schematic diagram of the positive pressure capsule of the invention in the stomach under digestion after administration.
  • the purpose of present invention is to provide a method of manufacturing a positive pressure capsule and said method comprises following steps:
  • Step 1 place the capsule to be filled in a positive pressure or low temperature environment
  • Step 2 fill the capsule with drug and retain the internal space containing bubbles
  • Step 3 seal the capsule and ensure no opening is found on the surface to prevent gas leak.
  • the positive pressure environment mentioned above refers to the environment with a more than one atmosphere pressure and one atmosphere pressure is equivalent to the international unit 1 atm, 1013hPa, or 76cm-Hg.
  • the bubbles mentioned above shall be retained to a level that does not affect drug administration dose and limitation on the size of the bubble is not necessary; in addition, said gas shall not affect the drug and content enclosed.
  • the low temperature environment mentioned above refers to a temperature lower than 25°C.
  • the shape of the positive pressure capsule mentioned above can be spherical, oval, long oval, tubular and polyhedral capsule and though the size of said capsule is not specified the content shall be adjusted to within the range from 1 mg to 10 g.
  • the raw material of the capsule of the invention is a reversible gelling substance, even after drying.
  • Said substance for example, made by HPMC, gelatin, agar, starch, alginic acid and guar gum, and is preferably a material containing gelatin or HPMC and a plasticizer.
  • the materials of the capsule may include additives such as a sunscreen, if necessary.
  • the gelatin mentioned above refers to gelatin obtained from hydrolyzed collagen extracted from animals such as cattle and pig. Also, to be used as the reversible gelling substance, the gelatin must be subjected to further treatments including alkali treatment, acid treatment or chemical modification. Acid treatment means hydrochloric acid or sulfuric acid is used as the hydrolytic agent; alkali treatment means alkaline salts such as lime is used as the hydrolytic agent; and chemically modified gelatin refers to gelatin obtained after the amino group of the gelatin reacts with organic acids such as succinic acid or phthalic acid.
  • the plasticizer mentioned above includes but is not limited to glycerol, sorbitol, maltose, glucose, polysaccharides, sucrose, xylitol, mannitol, propylene glycol, and polyethylene glycol and the like.
  • the sunscreen mentioned above includes but is not limited to caramel, titanium oxide, iron oxide and the like.
  • the form of the capsule filling of the invention is not specified and can be in liquid, suspension, paste, powder or granule.
  • the thickness of the hard capsule of the invention is not subject to any limitation only if it is thick enough to allow the capsule to exert its function. However, a thickness between 0.01 to 5 mm is better and the preferable thickness is 0.05-1mm.
  • the capsule of the invention can be used for production of pharmaceutical products, pharmaceutical product under registration, food and cosmetics, based on the composition of the filling.
  • the pharmaceutical products include but are not limited to the following products: vitamins, antipyretics, analgesics, anti-inflammatory agents, anti-ulcer agents, cardiotonics, anticoagulants, hemostatic agents, anti-resorptive agents, inhibiting angiogenesis agents, antidepressants, anti-tumor agents, antitussives, muscle relaxants, antiepileptic agents, anti-allergic agent, arrhythmia therapeutic agents, vasodilators, antihypertensive diuretics, therapeutic agents for diabetes, anti-tuberculosis agents, hormones, anti-bacterial agents, anti-fungicides and anti-viral agents but are not limited to the abovementioned groups of pharmacological action and all active ingredients that have relatively poor solubility in water are the objects of this invention. Active insoluble substances are preferred.
  • the method for manufacturing the positive capsule provided in the invention comprises following steps:
  • Step 1 place the capsule in a positive pressure environment and the environment shall have more than 1 atmosphere of pressure;
  • Step 2 under the positive pressure condition, fill the capsule with drug (5) ;
  • Step 3 seal the capsule body (1) and ensure no opening is found on the surface to prevent gas leak, but retain the bubbles (2) inside.
  • Step 4 return the capsule to normal environment, i.e. 1 atmosphere of pressure and becomes a positive pressure capsule.
  • a gas can be injected to allow the air room contain the injected gas (2) followed by sealing the capsule.
  • the positive pressure capsule after ingestion by the user ans when entering stomach for digestion, will release the drug (5) contained when the capsule is destroyed to a certain degree and the positive pressure is sufficient to break the capsule and form an opening (Fig. 3A and Fig. 3B) .
  • Step 1 place the capsule in a low temperature environment and the low temperature condition shall be lower than 25°C;
  • Step 2 under the low temperature condition, fill the capsule with drug (5) ;
  • Step 3 seal the capsule body (1) and ensure no opening is found on the surface to prevent gas leak, but retain the bubbles (2) inside.
  • Step 4 return the capsule to normal environment, i.e. room temperature, and the internal of the capsule will have more than 1 atmosphere of pressure and becomes a positive pressure capsule.
  • a gas can be injected to allow the air room contain the injected gas (2) followed by sealing the capsule.
  • the positive pressure capsule after ingestion by the user and when entering stomach for digestion, will release the drug (5) contained when the capsule is destroyed to a certain degree due to increased pressure caused by body temperature and the positive pressure is sufficient to break the capsule and form an opening (Fig. 3A and Fig. 3B) .
  • the capsule is a sealed capsule and the capsule must be a sealed capsule body (1) .
  • the method for sealing capsules can be the adhesion line (3) on the capsule body shown in Fig. 1, or the adhesion area (4) on the capsule body shown in Fig. 2 and said adhesion area is a sealed area and is formed after partial melting of the capsule body.
  • present invention is not limited to the method for capsule sealing for manufacturing sealed capsules and the embodiments are provided for the purpose of demonstration that the positive pressure capsule of the invention must be a sealed capsule rather than limitation.
  • present invention not only provides a novel method, but also discloses a number of improved features of technologies as described above. Therefore, the invention meet the requirements of novelty as well as non-obviousness (Article 33 (2) PCT or 33PCT (2)) . The applicant respectfully requests a favor on approval of the patent.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une capsule à pression positive et son procédé de fabrication. Le procédé comprend l'injection d'un médicament par l'ouverture de la capsule puis la fermeture de la capsule. L'intérieur de la capsule contient un espace d'air de façon à former une capsule à pression positive. Les caractéristiques de la capsule à pression positive sont des soudures par adhésion et des médicaments liquides peuvent être introduits à l'intérieur d'une telle capsule. La capsule est une gélule dure et la matière première de la capsule est la gélatine ou le HPMC.
PCT/CN2015/088634 2015-08-31 2015-08-31 Capsules à pression positive et procédé pour les fabriquer Ceased WO2017035747A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2015/088634 WO2017035747A1 (fr) 2015-08-31 2015-08-31 Capsules à pression positive et procédé pour les fabriquer

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2015/088634 WO2017035747A1 (fr) 2015-08-31 2015-08-31 Capsules à pression positive et procédé pour les fabriquer

Publications (1)

Publication Number Publication Date
WO2017035747A1 true WO2017035747A1 (fr) 2017-03-09

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Application Number Title Priority Date Filing Date
PCT/CN2015/088634 Ceased WO2017035747A1 (fr) 2015-08-31 2015-08-31 Capsules à pression positive et procédé pour les fabriquer

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4312347A (en) * 1980-02-25 1982-01-26 Iowa State University Research Foundation, Inc. Positive pressure drug releasing device
US4609403A (en) * 1984-03-12 1986-09-02 Warner-Lambert Company Foam soft gelatin capsules and their method of manufacture
CN1427765A (zh) * 2000-03-01 2003-07-02 Pvaxx技术有限公司 用于吹塑聚乙烯醇胶囊的方法和装置和吹塑的聚乙烯醇胶囊
CN1730118A (zh) * 2005-08-19 2006-02-08 华南理工大学 化学反应气压式微胶囊药物释放方法及其装置
TWM511327U (zh) * 2015-08-03 2015-11-01 Garry Tsaur 正壓膠囊

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4312347A (en) * 1980-02-25 1982-01-26 Iowa State University Research Foundation, Inc. Positive pressure drug releasing device
US4609403A (en) * 1984-03-12 1986-09-02 Warner-Lambert Company Foam soft gelatin capsules and their method of manufacture
CN1427765A (zh) * 2000-03-01 2003-07-02 Pvaxx技术有限公司 用于吹塑聚乙烯醇胶囊的方法和装置和吹塑的聚乙烯醇胶囊
CN1730118A (zh) * 2005-08-19 2006-02-08 华南理工大学 化学反应气压式微胶囊药物释放方法及其装置
TWM511327U (zh) * 2015-08-03 2015-11-01 Garry Tsaur 正壓膠囊

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