TWI718100B - Positive pressure capsule and manufacturing method thereof - Google Patents

Abstract

The present invention relates to a positive pressure capsule and a manufacturing method thereof. The positive pressure capsule is formed by injecting fillers (such as drugs) into the opening of the capsule, sealing the capsule and containing a gas space inside. The positive pressure capsule is characterized by tight seams and filling with liquid powder and other fillers. The capsule can be a hard capsule, and the raw material can be gelatin or hydroxypropyl methylcellulose (HPMC).

Description

Positive pressure capsule and manufacturing method thereof

The present invention relates to a positive pressure capsule and a manufacturing method thereof. The positive pressure capsule can accelerate the destruction of the capsule to form a rupture and accelerate the release of the filling material (such as medicine). The characteristic of the capsule is that the sealed capsule contains gas and the internal pressure is positive. Pressure.

Capsule is a rapidly developing pharmaceutical dosage form with a thickness of about 0.1-0.7 mm. It is widely used in medicines, health foods and other internal medicines. It has the advantages of convenient storage, accurate dosage, controllable drug release, etc., and can cover up the defects of the active ingredients of the drug. Odor and maintain the activity of the drug, so it is easy for users to accept.

The capsule dosage form can seal the filling inside the capsule. Due to its sealing feature, the medicine in the capsule can avoid the decrease in activity or moisture due to contact with the outside air and moisture, so it remains stable for a long time.

Certain pharmaceutically active substances may have biopharmaceutical or physicochemical properties that make it difficult to formulate into commercially acceptable formulations. However, such substances can be administered in the form of a liquid carrier medium. 1,2-propanediol (1,2-propanediol) and dimethylisosorbide (dimethylisosorbide) as solvents have great potential for such carrier media. The composition of the carrier medium allows it to form an emulsion in the stomach, thus facilitating the absorption of the medicinal active substance. The carrier medium must be accurately prepared so that it does not affect the composition of the drug and does not destroy its beneficial nature. The solubilizing properties of the drug carrier may change the properties of the active substance and cause it to precipitate, resulting in insufficient dosage for the patient. The emulsifying properties of the drug carrier may also be changed, and an emulsion may not be formed in the stomach during administration, and the pharmaceutically active substance may not be properly absorbed.

This liquid formula encapsulated in a capsule provides a very convenient method of administration for this medicinal active substance. However, commercially acceptable liquid-filled capsule products are also accompanied by difficulties that limit the availability of this approach.

Capsules used in medicine can be divided into hard capsules and soft capsules. Hard capsules (hereinafter referred to as hard capsules) can be filled with solid medicines such as powder or fine particles, and soft capsules (hereinafter referred to as soft capsules) can be filled with liquid medicines such as liquid medicine. .

The capsule materials can be gelatin, sorbital, hydroxypropyl methylcellulose (HPMC), opaque food coloring or other additives.

The raw material for traditional capsule manufacturing is gelatin, which is a protein or peptide extracted from the epidermis, bone, or connective tissue of animals, and contains collagen. After boiling in water, a hydrophilic, light yellow protein layer can be obtained, which is gelatin.

Another frequently used capsule material can be hydroxypropyl methylcellulose, which is also simplified as hydroxypropyl methylcellulose (HPMC). It is a viscous polymer that is often used in oral medicines. Excipients, emulsifiers, thickeners, suspending agents or alternatives to gelatin. After the cellulose is treated with alkali, the alkoxy anion generated by the deprotonation of the hydroxyl group can be added to propylene oxide to form hydroxypropyl cellulose ether; it can also be condensed with methyl chloride to form methyl cellulose ether. When the two reactions proceed simultaneously, hydroxypropyl methylcellulose is produced.

There are also many alternatives to capsule raw materials, including seaweed extracts or polysaccharide gums As an alternative raw material, plant-based raw materials can avoid cross-linking reaction with the animal protein contained in the capsule, and can maintain the strength of the capsule body. Because of the increasing popularity of mad cow disease in the United States in recent years, improved soft capsule raw materials have gradually received attention . Other alternative raw materials, such as agar gum, water-soluble etherified starch derivatives, HPMC, carrageenan, etc., have gradually gained market share.

One of the purposes of capsule improvements is to improve the bioavailability of pharmaceuticals. The active ingredient can be quickly released in liquid form as soon as the capsule is ruptured. Unlike the tablet composition, it is not necessary for the capsule to disintegrate completely in order for the active ingredient to become an absorbable state. At the same time, relatively insoluble active ingredients can be dispersed in a liquid carrier to provide faster absorption, such as a solution of a hydrophobic drug in a hydrophilic solvent; during digestion, the capsule will burst in the stomach, and Hydrophobic drugs can be dispersed in the gastric juice.

However, it is a common problem that capsules are slow in the process of disintegration. Studies believe that the slow disintegration of capsules is mainly caused by the cross-linking reaction of gelatin. Since the amino acids in the gelatin molecule are prone to oxidation to form aldehyde groups, the formed aldehyde groups can undergo cross-linking reactions with surrounding amino acids to form a three-dimensional network structure of intramolecular/intermolecular interconnection, resulting in increased gelatin molecular weight, structural stability, and water solubility Decreased sex, resulting in slow disintegration of the capsule. To solve the problem of capsule disintegration, the main solutions are: 1. Add antioxidant, 2. Adjust capsule formula and change the proportion of ingredients such as water and plasticizer, 3. Use raw materials that are less prone to oxidation.

In order to solve the aforementioned shortcomings that the capsule is not easy to disintegrate and affect the bioavailability of the drug in the gastric juice, the inventor has bothered to devise and develop the present invention.

In order to achieve the above-mentioned purpose of the invention, the present invention provides a positive pressure capsule, which utilizes the characteristic of the internal pressure of the capsule to be positive pressure to accelerate the destruction and disintegration of the capsule in the stomach after being taken. This speeds up the release of fillers (such as drugs) to facilitate the absorption of fillers and use them by organisms.

Wherein, the capsule may be a sealed capsule.

Among them, the internal pressure of the capsule must be positive pressure and greater than one atmosphere.

Wherein, the capsule contains gas, and the gas can be oxygen, helium, nitrogen, or carbon dioxide or a mixture of the above gases.

Wherein, the raw material of the capsule can be gelatin, which is a hydrolysate of animal collagen.

Among them, the capsule material can be hydroxypropyl methylcellulose (HPMC).

Among them, the capsule material may further include agar, starch, alginic acid, guar gum, and pharmaceutically acceptable additives such as sunscreens and plasticizers.

Wherein, the gelatin may be alkali-treated gelatin, acid-treated gelatin, or chemically modified gelatin.

Wherein, the plasticizer can be selected from the group consisting of glycerol, sorbitol, maltose, glucose, polysaccharide, sucrose, xylitol, mannitol, propylene glycol, polyethylene glycol.

Wherein, the sunscreen can be selected from the group consisting of caramel, titanium oxide, and iron oxide.

Among them, the filling of the capsule can be liquid, suspension, paste, powder, granule, etc.

In order to achieve the aforementioned purpose of the invention, the present invention provides a positive pressure capsule manufacturing method, which is to fill the capsule under a positive pressure environment, and then seal the capsule, wherein the air bubbles are retained in the capsule, and the finished product of the capsule is positive under the atmospheric pressure environment. Press the capsule.

In order to achieve the aforementioned purpose of the invention, the present invention provides another positive pressure capsule manufacturing method, It is filled in a low-temperature environment, and the above-mentioned low-temperature environment is lower than 25° C., and then the capsule is sealed, and a bubble is retained in the capsule. The finished product of the capsule is a positive pressure capsule under a normal temperature environment.

1: Capsule body

2: The capsule contains positive pressure gas or bubbles

3: Capsule body joint line

4: Capsule body junction area

5: Filling inside the capsule

Figure 1 is a schematic diagram of the positive pressure capsule of the present invention.

Figure 2 is another schematic diagram of the positive pressure capsule of the present invention.

Figure 3A is a schematic diagram of the positive pressure capsule of the present invention when it has not been digested in the stomach after being taken.

Figure 3B is a schematic diagram of the positive pressure capsule of the present invention being digested in the stomach after being taken.

All technical and scientific terms described in this specification, unless otherwise defined, have meanings commonly understood by those skilled in the art. The present invention is illustrated by the following examples, but the present invention is not limited by the following examples. The materials used in the present invention are all commercially available and easy to obtain. The following are only examples of available pipelines.

The object of the present invention is to provide a method for manufacturing a positive pressure capsule. The method includes the following steps: Step 1, placing the environment for filling the capsule in a positive pressure environment or a low temperature environment; Step 2, filling the filling into the capsule and keeping it There is a space with bubbles inside; Step 3, seal the capsule body so that there are no openings on the surface to avoid gas leakage.

Regarding the aforementioned positive pressure environment, it refers to an environment greater than one atmosphere, and one atmosphere is equivalent to 1atm, 1013hPa, or 76cm-Hg in the International System of Units.

Regarding the aforementioned bubbles, the bubble is based on the principle that it does not affect the dosage of the drug, and there is no The bubble size needs to be specially limited; the gas can be a gas that does not affect the filling.

Regarding the aforementioned low temperature environment, it is lower than 25°C.

Regarding the aforementioned positive pressure capsule, its shape can be spherical, oval, oblong, test tube, angular, etc.; although its size is not particularly limited, the amount of filling can be adjusted to the range of about 1 mg to 10 g That's it.

The raw material of the capsule of the present invention is a substance that still has the properties of reversible gelling even after drying. This substance, for example, is formed of HPMC, gelatin, agar, starch, alginic acid, guar gum and other gum substances. It is made of gelatin or HPMC, and plasticizers as the raw material of the capsule. good. In addition, the capsule raw material system may contain additives such as sunscreens as needed.

Regarding the aforementioned gelatin, it is possible to use gelatin obtained from animals such as cattle, pigs, and hydrolyzed and extracted collagen. In addition, gelatin having the aforementioned reversible gel properties includes alkali treatment, acid treatment, or chemical modification (chemical modification) gelatin. Acid-treated gelatin is the hydrolyzing agent using hydrochloric acid or sulfuric acid; alkali-treated gelatin is the hydrolyzing agent using alkalis such as lime; chemically modified gelatin is the combination of the amine group of the gelatin and succinic acid or phthalic acid (phthalic acid) and other organic acid reaction.

Regarding the aforementioned plasticizer, it may include, but is not limited to, glycerol, sorbitol, maltose, glucose, polysaccharides, sucrose, xylitol, mannitol, propylene glycol, polyethylene glycol, and the like.

Regarding the aforementioned sunscreen, it may include, but is not limited to, caramel, titanium oxide, iron oxide, and the like.

The form of the capsule filling material suitable for the present invention is not limited, and can be liquid, suspension, paste, powder, granular, etc.

The thickness of the hard capsule of the present invention only needs to be able to perform the function of the capsule, and is not particularly limited, but the thickness is preferably 0.01 to 5 millimeters (mm), and the thickness is preferably 0.05 to 1 mm.

The capsule of the present invention can be used for pharmaceuticals, quasi-drugs, foods, cosmetics, etc., depending on the composition of the filling.

Regarding the aforementioned filler, it may be a medicine or a quasi-drug, and the medicinal ingredient filled in the capsule of the present invention is not particularly limited as long as it does not impair the function of the capsule. Drugs include, but are not limited to, vitamins, antipyretics, analgesics, anti-inflammatory agents, antiulcer agents, cardiotonic agents, anticoagulants, hemostatic agents, anti-bone resorption agents, angiogenesis inhibitors, antidepressants, anti-inflammatory agents, etc. Tumor agents, antitussives and sputum agents, muscle retardants, antiepileptic agents, antiallergic agents, arrhythmia therapeutics, vasodilators, antihypertensive diuretics, diabetes therapeutics, antituberculosis agents, hormonal agents, analgesics, and antibacterial agents Drugs, antifungal agents, antiviral agents, etc., but are not limited to the aforementioned pharmacological action groups, and all medicinal ingredients with relatively poor water solubility are the objects of the hard capsule of the present invention. It is suitable for active substances that are difficult to dissolve.

In conjunction with the schematic diagrams of the positive pressure capsules shown in Figures 1 and 2, the preferred embodiments of the present invention are described in detail as follows:

Example one

The method for manufacturing positive pressure capsules provided by the present invention includes the following steps: Step 1: Place the filled capsule environment under a positive pressure condition, the positive pressure condition needs to be greater than 1 atmosphere; Step 2: Under a positive pressure environment, Filler (5) is filled inside the capsule; Step 3: Seal the capsule body (1) so that there are no openings on the surface to avoid gas leakage, but air bubbles (2) are retained in it; Step 4: Return the finished capsule to the normal environment, that is, under one atmospheric pressure, and the inside of the capsule can be greater than one atmospheric pressure and become a positive pressure capsule.

In the aforementioned positive pressure capsule, before or at the same time as the capsule body (1) is sealed, another gas can be injected so that the gas chamber is the injected gas (2), and then it is sealed.

The positive pressure capsule, after being taken by the user, enters the stomach for digestion, and when the capsule disintegrates to a certain extent, when the positive pressure is sufficient to break through the capsule to form a rupture, the purpose of releasing the filler (5) can be achieved (section 5) 3A, 3B).

Example two

The method for manufacturing positive pressure capsules provided by the present invention includes the following steps: Step 1: Place the filled capsule environment under a low temperature condition, which needs to be lower than 25°C; Step 2: Put the filling under a low temperature environment (5) Fill the inside of the capsule; Step 3: Seal the capsule body (1) so that there are no openings on the surface to avoid gas leakage, but retain air bubbles (2); Step 4: Return the finished capsule to the normal environment At room temperature, the inside of the capsule can be greater than one atmosphere and become a positive pressure capsule.

In the aforementioned positive pressure capsule, when the capsule body (1) is sealed, another gas can be injected so that the air chamber is the injected gas (2), and then it is sealed.

The positive pressure capsule, after being taken by the user, when it enters the stomach for digestion, the pressure in the capsule is further pressurized due to body temperature. When the capsule disintegrates to a certain degree, the positive pressure is enough to break through the capsule to form a breach. The purpose of releasing the filler (5) (Figure 3A, Figure 3B).

This capsule is a sealed capsule, and the capsule must be a tightly sealed body (1). The bonding method can be the capsule body joint line (3) shown in Fig. 1 or the capsule body joint area (4) shown in Fig. 2. The joint area is formed after a part of the capsule is melted. However, the implementation of this case is not limited to the way of joining into a sealed capsule. The purpose of the schematic diagram is only to illustrate that the positive pressure capsule of the present invention must be a tightly sealed capsule.

The above detailed description is a specific description of the possible embodiments of the present invention, but the embodiment is not intended to limit the scope of the patent of the present invention. Any equivalent implementation or modification that does not deviate from the technical spirit of the present invention should be included in this case. In the scope of the patent.

The above-mentioned multiple functions are in fact fully in line with the statutory requirements for invention patents for novelty and advancement. You file an application in accordance with the law, and I implore your bureau to approve this invention patent application to encourage invention.

1: Capsule body

2: The capsule contains positive pressure gas or bubbles

3: Capsule body joint line

5: Filling material inside the capsule

Claims (8)

A positive pressure capsule, comprising: a body, which is hollow; a filler, which is filled in the body; and a bubble, which is arranged in the body, and the air pressure of the bubble is greater than one atmosphere; wherein the positive pressure The thickness of the shell of the capsule is 0.05-1mm; the gas of the bubble can be helium, nitrogen, carbon dioxide or a gas that does not react with the filling. For example, the positive pressure capsule of the first item in the scope of patent application, the capsule can be spherical, oval, oblong, test tube, or angular. For example, the positive pressure capsule of the first item in the scope of patent application, the raw material of the capsule is gelatin or hydroxypropyl methylcellulose (HPMC). For example, the positive pressure capsule of the first item in the scope of patent application, the raw materials of the capsule may further include agar, starch, alginic acid, guar gum, and pharmaceutically acceptable plasticizers or sunscreens. For example, the positive pressure capsule of item 3 of the scope of patent application, the gelatin can be alkali-treated gelatin, acid-treated gelatin, or chemically modified gelatin. For example, the positive pressure capsule of item 4 of the scope of patent application, the plasticizer can be selected from the group consisting of glycerol, sorbitol, maltose, glucose, polysaccharide, sucrose, xylitol, mannitol, propylene glycol and Polyethylene glycol. For example, the positive pressure capsule of item 4 in the scope of patent application, the sunscreen can be selected from the group consisting of caramel, titanium oxide and iron oxide. For example, the positive pressure capsule of item 1 in the scope of patent application, the filling of the capsule can be liquid or suspended Medical composition or health food in the form of powder, paste, powder or granule.

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