TW200422162A - Method for manufacturing hard non-gelatin pharmaceutical capsules - Google Patents

Abstract

The present invention provides a method for manufacturing a non-gelatin hard capsule shell. The hard capsule shell is made by a heat-melting method which involves heating a capsule forming composition (preferably in powdery form) in a mold, followed by insert a pestle into the mold to coat the melted forming composition onto the pestle. The hard capsule thus formed, after hardened and dried, is removed from the pestle. This method has the conventional "dip molding method" for not requiring the capsule forming composition to be predissolved in solution so that no solvent is used in preparing the capsule forming composition. Also, by inserting a pestle into a mold, a pressure is imposed so as to ensure uniform coating of the capsule forming composition to the pestle. The present invention also provides a capsule forming composition which comprises a polymer and optionally a plasticizer and an apparatus for making the non-gelatin hard capsule shell.

Description

200422162 V. Description of the invention (1) [Technical field to which the invention belongs] The present invention relates to a method for preparing non-gelatin materials. The hard capsule is heated by a thermal fusion method in a hard capsule formula (using powder, the method includes inserting a mold into a capsule so that the capsule-forming composition is formed thereon), and then the pestle is hardened and dried. Remove ^ 盖 T from the mill. Hard capsule warp. The polymer is made of fibers, capsules, and molded derivatives, ethylene polymers, and poly :; primes; ^ 2 ;; dilute or acrylic acids or alginates. Finally, Ben: Cantonyl: 2--2-oxazoline). A device for preparing hard capsules [Previous technology] Medicinal capsules are called hard capsules. Capsules are often made of gelatin. Preparation of by-products of non-alcohol, opalescent agent, dyeing agent, and pigment, connective tissue of collagen protein. You can get a good structure of hydrocolloid by using ’. The general process is a gelatin solution dry gelatin material capsule attached to the mold, such as Warner-Lane, which has a flexible filling body and lid or hard shell capsule, and the most commonly used medicinal additives are plasticizers such as glycerin and sorbus. Or other additives can be added. Gelatin is a colorless or yellow-gray protein that is boiled in water by hydrolyzed animals that contain collagen, preferably animal bones, animal skin, and collagen-containing substances that are boiled in water. "'The technology for preparing gelatin material capsules has been immersed in an aqueous gelatin solution and then taken out. After sticking, it will be a plastic shell. Some representative pages 6 200422162 V. Description of the invention (2) PRE-FITTM, SNAP of Burt Company -FITTM and CONI-SNAPTM and other series of hard gelatin material capsules and Skeler's Lox_ITTM hard gelatin material capsules. However, the preparation and prohibition of gelatin is made by using or using disease capsules such as cattle brain. Capsule pigs eat Indian gelatin to supplement sponge-like disease. A gelatin-soluble cellulose derivative patent method No. 2,526, method or "immersion sequence" is prepared in place of gelatin in advance. This method is to extract the fiber ether solution and place it afterwards. Tablets are firstly provided in a low-temperature-dried capsule after peeling Mofei. The patent claims that the source of gelatin is animals (such as cows, pigs, etc.). It is not used by consumers such as vegetarians, Jews, and meat. And pigs ’by-products are accepted by Muslims. And amateurs do n’t consume cattle and cow ’s by-products. These people do n’t like capsules or use gelatin capsules as medicine. I feel uncomfortable. Recently, there is also inter-species pollution, disease, the so-called outbreak of BSE or "mad cow disease", which infects cattle and then transfers them to humans. Therefore, the doubts about the use of gelatin materials and the tendency to use capsules of other substances taken from nature or synthetics have also become apparent. Medicinal capsules prepared outside are already known techniques, and capsules made using aquatic organisms are typical and widely used. For example, in the United States 6 8 3, Murphy has revealed the process of preparing medical capsules of methylcellulose material called "impregnation method" in 950, first preheating to 40-8 0 t. The capsule forming mold / tablet is immersed and kept below 10-3 (TC; the mold plate is maintained in an oven with a preset extraction degree higher than 40-80 t, and the temperature of the mold t is gradually increased until the coating of the mold plate is coated The layer is dried to the required size, and then the main body and the lid are aligned. The method for the cellulosic material capsule is the original special dry-free process using far-red light and cooling with air.

Page 7 200422162 V. Description of the invention (3) According to the US patent No. 2, 5 26, 683 Murphy non-disclosure, the capsules of methylcellulose materials have the advantages over the inherent gelatin materials: Advantages: Resistant as well in very humid environments ^: Excellent stability. However, the disadvantage of this type of capsule is that it cannot be dissolved in the intestinal tract within the body: two hours. U.S. Patent No. 4,001,211 Shaka Jie * Fiber "and medical capsules and gels made from propylcellulose materials. Wei Mi is soluble in cold water but insoluble in hot water. Aqueous solution ^, suddenly As the viscosity increases, the colloid also becomes sticky: ㈡ == dipping method in which the die is placed in a mixture of water-soluble methyl and C2_C3 fired base fiber coating solution. A mixture of low-viscosity methylcellulose and cellulose Provides properties suitable as a dipping solution, suitable body elasticity, suitable capsule insolubility, etc. US Pat. No. 4,9 9 3, 1 3 7 wooden tray reveals a capsule made by improving the method of Shaka ::. The immersion of the immersed mold into water with controlled temperature to form a colloid. U.S. Patent No. 5,698,155 Grossworth et al. Disclose the preparation of a pharmaceutical capsule from a gelatinous fiber ether composition and the use of a main mold. Method and equipment for preparing capsules, such as molds and lid molds. The method includes: heating the molds, immersing the molds in an aqueous solution containing cellulose, so that the solution forms gelatin on the molds, removing the molds, and placing the molds. A gelatinous solution on the surface forms after drying The bag main body and the lid portion. US Patent 5, 756, 123, Yamamoto et al., Discloses a capsule shell containing ·

200422162 V. Description of the invention (4) (Based on heavy and heavy) water-soluble cellulose derivatives based cellulose (hidden), as a gelling agent 0 03 ~ 0 t tally carrageenan 'and as a side glue Of coagulant. 14 ~ 319 mixed with gelling agent in water to form Δζ /. The capsule shell was dried by the HPMC type method and formed into a gelatin :: Γ: -like immersion casting method. The novelty of making "capsules is hot and melted: there are polymers and non-essential additive plasticizers, which do not contain any melting. And the pestle is heated after being prayed in; = plus :: force after casting: heat to! Shape The pestle of the composition is taken off at will. Covered with capsules: It does not contain any gelatin solution at all. Immersion: The difference in the coating method is that it does not contain the previously entered coating method. The capsule shell made by this method Also like wrinkles, star opening; {corpse # Yuzhi capsule shells have the common madness': star-shaped tail, and wavy surface.-More than one capsule cap or capsule main capsule forming composition added at least one Plastic molds and molds with a diameter smaller than the shape of the openings; (2) The shape of the composition dissolves the product produced by the mouth, ^ mouth of the pestle is heated to a temperature higher than the capsule to form a capsule forming combination ^ are included in your prayers Press the pressure on the pestle of the household mold to remove the pestle from the mold and apply it on the heated pestle; (4), Part V and the capsule forming group dried on the pestle 200422162 V. Invention Instructions (5) ::: (6) Plasticizers that have been dried in capsules. If the capsules become h, add them The proper solvent is any liquid that can dissolve the spleen hair, the middle skin, and the red rubber capsule forming composition, such as K, any buffer, or any solvent that can be used for general irritation of glandular and ancient toasts. The invention adopts the hot-melt method, and the organic form of the product is powder form without any solvent: == knee capsule cost Although the mold and pestle used in the invention can bear any substance that can tolerate the melting point of the capsule forming composition, the capsule The stainless steel is better. The melting point of the rubber capsule group 5 is affected by the polymer used to make the capsules. The polymer used to make the hard capsule shell in the invention is divided into the following substances: (1) cellulose Or cellulose-based substances, including but not limited to cellulose, cellulose esters, cellulose ethers, cellulose nitrates, triacetates, cellulose phthalates, methylcellulose, ethmidine Vitamins, hydroxypropylcellulose, hydroxypropylmethylcellulose, and o-dimethylenol & 3 propylmethylcellulose. (2) polymers of acrylic acid or acrylic acid derivatives " " or copolymers , Including but not limited to polypropylene Acid, polymethacrylic acid, polyenoic acid-methacrylic acid), poly (methyl acrylate-methyl methacrylate), poly (ethyl acrylate-methyl methacrylate), poly (gasified ethyl acrylate ~ Methyl methacrylate-trimethylamino methyl acrylate. (3) Polyolefins include and are not limited to polyethylene, polypropylene, and polybutene. (4) Polyvinyl groups such as, but not limited to, polyvinyl chloride Ethylene, polyvinyl acetate, polyvinyl alcohol, polyphenylene, and polyacrylamide. In addition, polymers such as poly (2-ethyl-2melamine) or alginate salts can also be used to make capsules. Μ ·

Page 10

200422162 V. Description of the invention (6) It is used to make gums (glycerol, propylene diethyl ester, o-phenyl ether, diethyl ethyl alcohol, and triethyl glycerol). The present invention is also a polymer and a plastic material, and the capsule is better divided into capsules. In addition, the hard mold has at least one opening for heating the mold, and the capsule forming combination mold is opened so that the upper part has been heated, cooled, and dried. Finally, the device includes two mortars with a capsule shape (the diameter of the pestle is :first

The plasticizers formed by the pouch-forming composition include (f), limited to alcohol, polyethylene glycol (PEG 20 0-6000), o-benzyl, dibutyl diacetate, dibutyl sebacate, Citric acid formic acid, citric acid, tributylacetic acid, citric acid: osmium, castor oil, acetylated monoglyceride, and cypress oil (purely provided in a hard capsule shell. The capsule The shell includes one: a capsule-forming composition consisting of: a stomach polymer non-forming composition also does not include any solvent. Plasticity% Repair composition weight percentage of 0 ~ 40%, and ^ as Μυ · 〇1 ~ 2 〇〇 / 0 The preparation of the capsule shell is as follows: the shape of the capsule forming group and the shape of the capsule cap or the capsule shell body is smaller than the mold opening σ of the pestle plus the dew point temperature; the pressure makes the heating Zhiyan's melted capsule forming composition is evenly cast out of the pestle, so that the clay on the pestle = the pestle sample is removed and formed to form a rubber capsule shell: it can be used for preparing a hard capsule shell. The main parts, respectively * · · ⑴ mold, .... The shape of the lid or capsule shell And (2) Glue = j is also the main body of the capsule or capsule shell but it is equal to the inner diameter of the capsule shell to be prepared.) The mold is added to the capsule forming composition in the casting # This device places the scale mold inside, and then the casting mold, im 200422162 V. Description of the invention (7) 2 Molding composition, pestle-heat up to the capsule molding composition (make the f-shaped composition from powder to liquid); add character A, so that it is evenly coated on the pestle The capsule is formed into a group and dried. After removing it, a hard capsule shell will be obtained. R = i Morisan made of stainless steel as m Bu can also be equipped with Wenlu: the dolphin n: Hai 2 kiln is suitable to keep above Gelatin initial temperature ^ It is also suitable to dry it while still on the pestle: In addition, the pestle can be attached to a machine that can accelerate the in / out of the mold. The "capsule refers to the body and cover" in the present invention. The hard part of the ministry can be filled with capsules that can be filled. Mainly good: ϊThe method of making capsules of non-gelatin materials such as cellulose capsules has been obtained by you. The method of making capsules made of cellulose is called ^ main coating Method, which involves inserting a capsule cap or capsule body into a capsule combination In the liquid solution, the method invented by the present invention does not use the "impregnated molding composition in a cast made of stainless steel that can withstand high temperatures: melting", the capsule is heated in a pestle (also Suitable for: dry rust without removing the pestle to obtain a shaped capsule shell. The "I ί method" does not require a liquid solution containing a capsule forming composition: it is more advantageous, and is better than other methods. This The method is not as beautiful as the patent: Patent No. 2,526, 683 Murphy disclosed the steps of immersing the mold in the solution, withdrawing the solution at a preset speed, and continuously heating to gelatinize the capsule. 200422162

Save time and reduce costs. The capsule-forming composition used in the present invention is composed of a polymer and a plasticizer. In addition, bleaching agent, chromatin, and compound from% 丄 t knife ^ ^ ^, but Γ wood tincture Ba Jing and other additives can also be added as needed. There are four main polymers suitable for use in the formulation of the capsule-forming composition of the present invention, respectively: (丨) cellulose or cellulose derivatives; polymers or dimers of propylene or acrylic derivatives; (3) ethylene polymerization And (4) polyolefins. Alternatively, poly (2-ethyl-2-oxazoline) or alginate can be used in the formulation of capsule forming compositions. 2. Cellulose or cellulose derivatives suitable for preparing capsule shells include natural or artificial synthetics, such as: cellulose, cellulose ester, cellulose ether, cellulose nitrate, cellulose triacetate, phthalic acid fiber Acetate (CAp), methylcellulose, ethylcellulose, hydroxypropylcellulose (Hpc), hydroxypropylmethylcellulose (HPMC), and hydroxypropylphosphonium phthalate (HPMCP) ). The preferred cellulose polymers include hydroxypropyl cellulose (Hpc), propylene methyl cellulose (HPMC), phthalic acid cellulose acetate (CAp), and hydroxypropyl methyl phthalate素 (HPMCP). Propyl methylcellulose (UK National Formulary Book 8) and phthalic acid cellulose acetate (US Pharmacopoeia Book 18) are sometimes abbreviated as "this and CAP. Hydroxypropyl phthalate" Methylcellulose is written as HpMcp. There are now at least two doses or forms of HPMCP available on the market from Shin-Etsu Chemical Co., Ltd. in Tokyo, Japan. -55. HP-50 has 20 ~ 25% methoxy, 8 ~ 12% hydroxypropyl and

Page 13 200422162 V. Description of the invention (9) 20 ~ 27% hydroxyphenyl. HP-55 has 18 ~ 22 ° /. Methoxy group, 6 ~ 10% propyl group and 20 ~ 27 hydroxyphenyl group. HP-50 and HP-55 are soluble in water in alkaline environments. HP-50 is dissolved when the pH value is higher than 5, and HP-55 is dissolved when the pH value is higher than 5.5. Preferred polymers or copolymers of acrylic acid or acrylic acid derivatives include but are not limited to polyacrylic acid, polymethacrylic acid, poly (acrylic acid-fluorenyl acrylic acid), poly (methyl acrylate-methyl methacrylate), poly (Ethyl Acrylic Acrylic Acid-Methyl Acrylic Acid Methyl Acetate), Poly (Gas Acrylic Acrylic Acid-Methyl Methyl Acrylic Acid-Methyl Trimethylamino Propionate. For example, methacrylic acid and alkanes The copolymer of vinyl acetate and acrylic acid has the following unit structure:

Page 14 200422162 V. Description of the invention (10) ch3 CH2—-C-CH2-c-CHr c = o c c = o

OH

OR

OH

Among them, R is a lower alkyl group such as a methyl group or an ethane group. Methacrylic acid esters can be prepared according to many methods. Methacrylic acid / ester copolymers are also available in various dosages and forms. For example, Luo and Haas in Tokyo, Japan, and Eudragi tR series products containing fluorenyl acrylic / ester copolymers with various formulations, such as EudragitR-E, L, S, RL, RS, NE. The above copolymers are almost all soluble in water in an alkaline environment. EudragitR series products suitable for the present invention are EudragitR-RS100 and RL-100.

Eudragi tR L100 has a 1: 1 (methacrylic acid, methyl methacrylate) polymer and is sold in powder form. And Eudragi tR_slOO〇

Page 15 200422162 V. Description of the invention (11) Polymers of (methacrylic acid, methyl methacrylate) with a ratio of 1: 2 are sold as powder. EudragitR-L100-55 is a 1: 1 (methacrylic acid, ethacrylic acid) polymer and is also sold in powder form. EudragitR-E100 has a 2: 1 polymethyl methacrylate- (poly [butyl acrylate, (2-dimethylaminoethyl) methyl acrylate, ethyl methacrylate]), sold in pellet form For sale. EudragitR-RL100 has a 1: 2: 0.2 (ethyl acrylate, methyl methacrylate, trimethylamine chloride ethyl methacrylate) polymer and is sold in pellet form.

Eudragi tR-RS10 0 (ethyl acrylate, methyl methacrylate, trimethylamine ethyl methacrylate) polymer with 1 ·· 2 ·· 0 · 1 is also sold in pellet form. The fluorenyl acrylic acid / ester copolymer is an anionic copolymer and is often used for intestinal release drugs because it is soluble only in a pH value higher than 5.5. For example, the anionic copolymer EudragitR-S dissolves at pH 7.0, EudragitR-S or L also dissolves above 7.0, and EudragitR-RS is hardly soluble in water. Suitable ethylene polymers include, but are not limited to, polyvinyl chloride, polyvinyl acetate, polyvinyl alcohol, polystyrene, polypropylene. Polyolefins include, but are not limited to, polyethylene, polypropylene and polybutene. In addition, it is not necessary to add the polymer to the capsule forming composition

200422162 V. Plasticizer of Invention Description (12). Suitable plasticizers include (1) polyethylene glycols such as polypropylene glycol, polybutylene glycol, and polyethylene glycol (PEG) (200-6000); (2) organic esters such as diethyl phthalate (DEP), Dibutyl phthalate (DBP), dibutyl sebacic acid (DB S); (3) citric acid such as citric acid triester (TE C), acetyl triethyl citrate (ATEC), ethyl acetate醯 Tributyl citric acid (ATBC), tributyl citrate (TBC) and glycerol triacetate (triacetin); (4) oil / glycerin such as castor oil, ethyl alcohol, and purified coconut oil. Suitable plasticizers are polyethylene glycols (such as PEG 1000 and 4000), citrate triesters, tributyl citrate, and triacetin. The suitable component of the plasticizer in the capsule forming composition is 0 ~ 40% (by weight), and 0 · (Π ~ 20% is more suitable. [Embodiment] The following examples are given as examples, not for [Example 1] The steps for preparing a hard capsule shell are as follows: (1) 65 mg of hydroxypropyl cellulose (HPC) is added to a mold made of stainless steel with an opening, and the shape of the tweezers As the capsule cap or capsule body, the mold can have different sizes and sizes to meet the required dose, and the inner diameter of the mold is equal to the capsule shell diameter;

Page 17 200422162 V. Description of the invention (13) (2) The mold and the capsule-shaped pestle (also made of stainless steel) are heated to 160 C to completely resolve the HPC; the shape of the pestle can be the main body of the glue. , And its diameter is equal to the inner diameter of the capsule shell; (3) When the HPC is still molten, the pestle is prayed into the mold, and the HPC can be evenly coated on the pestle by pressing; (4) the mortar is made of Withdrawing from the mold, the extraction speed of the pestle can be accelerated by the connected extraction equipment; (5) The HPC coated on the pestle is dried and hardened, and the HPC can be dried to complete gelation in a kiln; (6) Remove the HPC from the pestle. [Example 2] The steps for preparing a hard capsule shell are as follows: (1) About 65 mg of hydroxypropyl cellulose (Hpc) as a polymer and about 7.2 mg of PEG 1 0 0 as a plasticizer (the plasticizer component is formed into a capsule) 10% by weight of the composition) mix; add the capsule-forming composition to a straight-opening mold; / (2) heat the mold and capsule-forming composition to £ 120; > (: until Hpc and pEG are completely melted; (3 ) When the HPC and PEG are still molten, the pestle is prayed into the mold, and the pressure can be applied so that the capsule forming composition can be evenly coated on the pestle;

Page 18, 200422162 V. Description of the invention (14) (4) Withdraw the pestle from the mold, the extraction speed of the pestle can be borrowed; Han Bei accelerates the extraction (5) The capsule forming group coated on the pestle The capsule-forming composition is dried in the kiln until the gum is completely dry and hardened. (6) The capsule-forming composition can be removed from the pestle. The size of the mold and the pestle is as described in the first embodiment. [Example 3] The preparation steps of the hard capsule shell are as follows: (1) 70 g of Eudragi tR RS1 〇〇 (man

Hi i (mr (T / EudragitR RS10 ° ^ # ^ ^ # t ^ ^ M ^ M ^ y A · Mouth-like knife heat UL 3 UL to remove the C _; add the rubber capsule composition into a mold with an opening The liver is finished and the mold is finished. 2) In the case where Eudragi tR RS100 and TEC are still melted, the pestle 'mold can be pressurized so that the capsule forming composition can be evenly coated on the pestle; 2 4 ) Withdraw the pestle from the mold, the extraction speed of the pestle can be increased by the connected extraction equipment; page 19 200422162 V. Description of the invention (15) (5) The capsule forming composition coated on the pestle is dried It can be hardened, and the capsule-forming composition can be dried to complete gelation during burning; (6) the capsule-forming composition is removed from the pestle. The size of the prayer mold and pestle is the same as that described in the first embodiment. [Example 4] The preparation steps of the hard capsule shell are as follows: (1) 70 gram of EudragitR RU〇〇 (as a polymer) was dissolved in propyl = ^ = EudragitR RU in acetone and 0.7 mg of screw Tributyl citrate (TBC) (as a plasticizer) is mixed to prepare a capsule-forming composition; the capsule-forming composition is heated to 5 (rc to remove acetone; the capsule-forming composition is added to a mold having an opening; (2) Heating the mold and capsule forming composition to 18 () RL100 and TBC completely melted; | j j3) When jldragitR RL100 and TBC are still melting, the pestle is poured into the mold, which can pressurize the capsule forming composition to average Coated on a pestle; Draw out from the research mold Λ prayer mold, 'The extraction speed of the pestle can be accelerated by a connected extraction device; 夂 (5) The capsule forming composition coated on the pestle is dried and hardened, and can be burned. Drying the capsule-forming composition in the kiln to complete gelation;

Page 20 200422162 Description of the invention (16) (6) The capsule-forming composition is removed from the pestle. The size of the mold and the pestle is the same as that described in the first embodiment. [Example 5] The steps for preparing a hard capsule shell are as follows: (1 L of 70 mg of hydroxypropyl methyl cellulose (HpMC) as a polymer and 7.8 mg of PEG 40 00 (as a plasticizer) (this plasticizer The amount is about 10% by weight of the capsule forming composition)) to prepare a capsule forming composition; adding the capsule forming composition to a mold having an opening; (2) heating the mold and the capsule forming composition to 200% Until jjpmc and peg are completely dissolved; (3) When the HPMC and PEG are still melted, the pestle can be pressed into the mold to pressurize so that the capsule forming composition can be evenly coated on the pestle (4) The pestle is cast from the mold Withdrawing speed can be set by the extraction speed of the pestle connected to the extraction; knife back C 5) The capsule forming composition coated on the pestle is dried and hardened, and the capsule forming composition can be dried in a kiln to completely gelatinize (6) Remove the capsule-forming composition from the pestle. The size of the mold and the pestle is the same as that described in the first embodiment. [Example 6] (1) Approximately 70 mg of poly (2-ethyl-2-minging) was used as a polymer and

Page 21 200422162

5. Description of the invention (17) As a plasticizer, about 7.8 mg of triacetin (TA) (the plasticizer component is 10% by weight of the capsule forming composition) is mixed to prepare a capsule forming composition; the capsule forming is combined Material into the mold with an opening; (2) heating the mold and the capsule forming composition to 120 ° C until the poly (2-ethylimide (3) in the poly (2-ethyl-2-oxazoline) & When the TA is still molten, the pestle is prayed into the mold, which can be pressurized so that the capsule forming composition can be placed on the pestle; J ^ (4) The extraction speed of the pestle from the mold; Capsule-forming composition coated on the pestle was dried by a connected extraction device. Dry the f-capsule-forming composition to completely gelatinize the capsule-forming composition in a ^ λ λ, λ, λ, p. The composition was removed from the pestle. 上 ί ί = The size is the same as that described in the example. The method of range is used as an example, not to limit the present invention.

Page 22 200422162 Schematic description

Page 23

Claims (1)

200422162 6. Scope of patent application [Scope of patent application] 1 · A method for preparing capsules made of non-gelatin materials, the method = adding at least one opening and the shape of the capsule cover or glue: U The capsule forming composition is composed of a polymer, The assembly adds a mold and a pestle having a diameter smaller than the opening diameter of the mold to the melting point of the capsule forming composition; ..., the main shirt is pressed into the heated mold to press into the heated mold to contact the capsule forming Composition '/ Withdraw the pestle coated with the capsule forming composition from the mold, cool and dry the capsule forming composition on the pestle; and remove the formed composition from the pestle. 2. The method as described in item 丨 of the scope of patent application, which is made of casting mold and stainless steel. The method described in item 丨 of the patent application range is π 其. The polymer is cellulose derivative. 34. The cellulose or cellulose derivative according to item 3 of the scope of the patent application, at least one selected from the group consisting of cellulose, cellulose ester, cellulose ether, cellulose nitrate, cellulose triacetate, and phthalic acid fiber. Acetate (CAP), methylcellulose, ethylcellulose, dibasic cellulose, hydroxypropylmethylcellulose, and hydroxypropylmethyl divinin phthalate. 5. The method according to item 1 of the scope of patent application, wherein the polymer is a polymer or copolymer of acrylic acid or acrylic acid. 6 · Acrylic acid or acrylic creature as described in item 5 of the scope of patent application show Page 24 200422162 At least one kind of polymer or copolymer self-polymerized acrylic acid, polymethacrylic acid, poly (acrylic acid-methacrylic acid), poly (methyl propionate to methyl methacrylate), poly (ethyl acrylate-methyl A polymer of methyl dienoate), poly (ethyl chloroacrylate-methyl methylpropionate-fluorenylaminomethyl acrylate. 7) The method as described in item 丨 of the patent application scope, which The polymer is a polyolefin and at least one is selected from the group consisting of poly6ene, polypropylene, and polybutene. 8 · As described in the first item of the patent scope of Shenyan, the polymer is an ethylene polymer, and at least One is selected from polyvinyl chloride, polyvinyl acetate, polyvinyl alcohol, polystyrene, and polypropylene. 9. The method as described in item 1 of Shenyan's patent, wherein the polymer is poly (2-ethyl-2-oxazoline) or alginate. 10 · The method as described in item 1 of the scope of patent application, wherein the polymer is mixed with a plasticizer. 1 1 · At least one of the plasticizers described in item 1 Q of the scope of the patent application is selected from polypropylene glycol, polybutylene glycol, and polyethylene glycol (PEG) (200-6000), diethyl phthalate, orthoben Dibutyl diformate, dibutyl sebacic acid, triethyl citrate, acetic acid triethyl citric acid, acetic acid tributyl citric acid, tributyl citrate, glyceryl triacetate, castor oil, ethyl acetate Tritiated monoglycerides and coconut oil. 12. · A capsule shell of non-gelatin material includes: a capsule-forming composition composed of a polymer and a plasticizer; a remote polymer non-gelatin, why the above-mentioned capsule-forming group does not include a solvent; the plasticizer component is about a capsule-forming combination 0% to 40% by weight. Page 25 200422162 VI. Patent Application Range 1 3 · The capsule shell of non-gelatin material as described in item 12 of the patent application range is a capsule molding composition added to a mold with at least two openings and a shape of a capsule capsule or capsule body , The mold and the mortar with a diameter smaller than the opening of the mold are heated to the melting point of the capsule forming combination, and the heated mortar is pressed into the heated mold to contact the capsule forming composition; The sample with the capsule forming combination was drawn out of the self-made mold; the capsule forming composition on the pestle was cooled and dried; and the dried capsule forming composition was removed from the pestle. ... c ’, 14. The capsule shell of a non-gelatin material as described in item 12 of the scope of the patent application, the composition of which is a cellulose derivative, and at least one selected from cellulose, cellulose vinegar ', and cellulose ether. , Cellulose nitrate, cellulose triacetate, o-benzyl dicarboxylic acid ^ Vitamin acetate, flat cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and hydroxypropyl phthalate Base cellulose. '^ Poly-A its polypropylene 15. The capsule shell of a non-gelatin material as described in item 12 of the scope of the patent application, the composition of which is a polymer or copolymer of acrylic acid or 0 acid derivative, and at least one selected from acrylic acid, poly Methacrylic acid, poly (acrylic acid-methamphenic acid, H-propionate methyl vinegar-methyl acetic acid methyl vinegar) 1 (acrylic acid ethyl alcohol 1 base acrylic acid methyl alcohol), poly (ethyl chloride acrylic acid Methyl acrylate-trimethyl amino methyl acrylate. 16. The polymer composed of a capsule shell of a non-gelatin material as described in item 12 of the scope of the patent application is a polyolefin, and there are a small number of polymers selected from the group consisting of polyethylene, Olefins and polybutenes 17. Non-gelatin material capsule shells as described in claim 12 200422162 Sixth, the scope of the patent application The composition of the polymer is ethylene polymer, and at least one kind is selected from polyvinyl chloride, polyvinyl acetate, polyvinyl alcohol, polystyrene and polypropylene. 1 8. The capsule shell of non-gelatin material as described in item 12 of the scope of patent application, the composition of which is poly (2-ethyl-2-oxazoline) or aginate. 19. The capsule shell of a non-gelatin material as described in item 12 of the scope of the patent application, the plasticizer is at least one selected from polypropylene glycol, polybutylene glycol, polyethylene glycol (PEG) (200-6000), orthobenzene Diethyl diformate, dibutyl isophthalate, monobutyl sebacic acid, triethyl citrate, ethyl triethyl citrate, ethyl dibutyl citrate, tributyl citrate, triethyl Glyceryl acetate, castor oil, acetylated monoglyceride, and coconut oil. 20. The non-gelatin material capsule shell as described in item 12 of the scope of the patent application, wherein the plasticizer component is about 0. 〇1 ~ 2〇21 · used to prepare non-gelatin material capsule shells. The device comprises: a mold having at least one opening and having a shape of a capsule or a capsule main body capable of carrying a capsule forming composition; and a mold having a diameter smaller than the opening of the mold into the mold, and the pestle and the mold are heated above the glue ;: Pestle may be suitable for prayer After the temperature is reached, the pestle is poured into the mold, and the composition is melted, and then the mold is withdrawn from the mold. Solution of the capsule forming composition 22. It is made of stainless steel as described in item 21 of the scope of patent application ^ 5 Hai mold and pestle 23. It is used to accelerate the capsule on the pestle as described in item 12 of the scope of patent application Forming group / 1 'can be equipped with a kiln for hardening and drying. 200422162 VI. Scope of patent application 2 4. The device described in item 12 of the scope of patent application can be added with a device to accelerate the speed of the pestle entering the mold and withdrawing the mold. Hi Page 28 200422162 Amendment Supplement I Invention Patent Specification Name of Inventor (3 persons in total) Chinese English 1ΓΊ (Chinese) (English) (Ci Residence House (Chinese) Non-gelatin material and its manufacturing system ^ MMHUU FOR MANUFACTURINGlURD non-gelatin pharmaceutical capsules' 1 · 陈Gan Lin2 · Φ Jianyuan3 · Liu Zhengxiong L 1 · Republic of China TW 2 · Republic of China TW 3.Republic of China TW Name or name (Chinese) Applicant (1 person in total) Name or Name (English) i Chinese and English ^ 居 户 i ίϊ 业 所) (t_ ^) f 业 所) (中文 5 Representative (Chinese) 1. No. 1191, Section 1, Zhongshan Road, Dajia Town, Zhong County, TW (This address is different from the previous applicant to your office) Representative (English) Page 1 200422162 III. $ 5 pages 200422162 V. Description of the invention (1) [The invention to which this invention belongs has law. The hard gelatin capsules are heated to make the capsules harden and dry. They are made of polymers and materials. The polymer derivative, ethylene or alginate is a good preparation. [Technical field] There is a telescoping capsule, the added cota is added with gelatin from water animal protein or yellow ash, and gelatin gelatin is used as a capsule. [Technical field] Related to the preparation of non-gelatin The material capsule is made by a thermal fusion method, and the square composition of the capsule shell (in the form of powder: f method includes forming a mold-shaped composition thereon) and then removing the pestle from the mill. It can be made into a cover. Hard capsules are made by adding plasticizers that are not necessary-cellulose or cellulose derivatives> capsules are combined with polymers, polyolefins, I (2-ethyl: 1 acid or acrylic acid. After you have been treated, ethyl ethyl ~ 2-oral oxazoline), the present invention also provides a medicinal capsule which is designed to fill the main body and the lid of a hard capsule. It is called a hard capsule. Gelatin material. Non-indispensable plasticizers such as glycerin and sorbitol, opalescent agents, colorants, pigments can be added. Preparation of animal by-products containing collagen, collagen, egg bones, animal skin, white seeds The connective tissue of the object. Boil the Buddha in water to get the protein that constitutes the hydrophilic color. ^-The material capsule technology has been fully constructed. The general process is to remove the mold solution and adhere it to the mold. Dry shell of gelatin solution. Some representative gelatin material capsules such as Warner ~ Lan. Page 6 V. Description of the invention (2) — Bert = Division's PRE-FITTM, SNAP-FITTM and CONI-SNAPTM series of hard gelatin material capsules Hexler ’s LOX-ITTM hard gelatin material is superior. However, since the source of gelatin is animals (such as cattle, pigs, etc.), the capsules are not used by consumers such as vegetarians, Jews, t ΐ ΐ pork and The by-products of pigs are accepted by Muslims. And, the two Indians do not consume cattle and by-products of cattle. These people do not use capsules made of magnetic glue or use knee capsules as ϊ 2. Qin Chong felt uncomfortable. Recently, there is also inter-species pollution, ® / cotton-like lesions, so-called BSE: or "mad cow disease tends to replace gelatin to make capsules. Other things The use of medicinal capsules made of gelatin other than gelatin is already a # 4 soluble cellulose derivative. Capsules are of the industry type n = known technology, and are prepared by using the "water method" or "dipping method". The method is to first pre-heat the fiber capsule solution of medical capsules which have been preheated to / 〇j〇 \ c, wood f1 ", and keep it lower than 丨 〇_3 = the capsule forming mold is immersed in ΪΪ; The input temperature is kept higher than 4 "0; =: It is neatly set that the drawn-out tablet is first in a low temperature state and then gradually increased, in the baking phase of w C, and the peeled-off capsule is peeled off before becoming two: ^ on the tablet The coating is dry. Dry: Preparation of methyl fiber provided by Fei; Material: Plastic body 2 and cover part for Heli's drying process in this patent makes the red 200422162 According to the American Nasal Methyl Cellulose ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, 2, 2, 6, 6 3, Murphy's non-disclosed method, has many advantages, such as the capsules of the natural light and bright materials, have more advantages Good stability and resistance in a very humid environment. However, the disadvantage of Ting Capsule is that it can not dissolve in the intestinal tract during body temperature and cold days. Shaka No. 4, 0 01, 211 reveals a medical capsule made of fibrous ether hot glue such as quasi-cellulose and propylcellulose. It is soluble in water but insoluble in hot water. =: It rises and falls again, and then increases in a narrow temperature and interval above the minimum viscosity temperature, and colloids also form. Shaka's capsule system is made by placing tablets into a mixture of water-soluble methyl and C2-C3 hydroxyalkyl cellulose ether, immersion method in immersion solution. A mixture of low-viscosity fluorene-based cellulose and acetylcellulose provides suitable immersion solution, Suitable properties such as insolubility of capsules. U.S. Patent No. 4, 993, 1 No. 37 A modified Shaka: Capsule made by the method. * Supports the formation of colloids in water with mold coating. Also controlled · U.S. Patent No. 5,698,155 Grossward et al. Revealed the gelatinous properties f The medicinal ether composition is used to prepare medicinal capsules, and the method and equipment for preparing capsules using the main mold sheet and the cover mold puller. The method includes: 2. Dipping the mold sheet in an aqueous solution containing cellulose to make the solution soluble孓 ,,; glue, remove the mold [the gelatinous solution on the surface of the mold = soil: the capsule body and the lid. Put the glue into the back to form the glue US Patent No. 5,756, 1 No. 23 Yamamoto et al. Disclosed-capsule Shell contains 200422162 V. Description of the invention (4) 98.7% (by weight) of water-soluble cellulose derivative based on methylcellulose (HPMC), Ni Yan_, Guo Jie · > η ^. With 79 · 6 ▽, ... Eastern 卩 丨 / ~ The cellulose derivatives are: hydroxypropyl methylcellulose (HPMC), as a gelling agent, 〇03 ~ 0.5% (Zhongli juice) antlers Glue, and potassium ion and / or calcium ion as a secondary gelling agent of 0 to 4-19 (by weight). The coagulant is mixed in water to form an aqueous solution, which is then obtained by drying the aqueous solution and forming a capsule shell by a general sinker-type method. &Amp; Bismuth = Mingzhong 'will provide a method for manufacturing a rigid transfer capsule; there are = :; :: Want to pouch; the material is added to a mold. The dagger is materialized. And the pestle is added to the mold: m is added to the mold and heated to melt the capsule forming composition can be evenly coated ::: grind: add pressure to make the shape combination The pestle of the object is followed by 4; on the pestle. The capsule is covered and removed from the pestle. The second party is allowed to dry and the capsule does not contain any gelatin at all: = the difference of the previous immersion coating method The point is that the capsule shells that do not contain the previous advance = two methods are also wrinkled, star-shaped surnames, and capsule A has common defects, [invention content ^ and wavy surface. The present invention provides a manufacturing method. The method includes: (i) adding one or more capsule caps of a hard capsule shell made of non-Guangjiao plastic material, and adding the capsule forming composition to a casting mold containing at least a plastic mold and a diameter of 22, and the shape of the two capsule bodies. (2) Warm production of dissolving the shaped composition, heating the open pestle to a temperature higher than that of a capsule to obtain a capsule-forming composition = at 3) pressing on the pestle that is cast into a mold to coat the dry sentence On the heated pestle; (4) 200422162 V. Description of the invention (5) _____ Remove the pestle from the mold; (5) cool and dry the material; (6) shape the dried capsules into multiple capsules And the capsule-forming composition contains a non-gelatin material removed from the pestle. The plasticizer. If the capsule-forming composition and the non-essentially added defined solvent are any, the glue can be better. The sergeant of the invention, any buffer, Or any combination of liquids, such as lotions. Because the invention uses the hot melt method, the organic-type composition in the method is in powder form and does not require any dissolution. , The conversion used in the present invention = chemical solution The composition has any melting point temperature, but the melting point of the composition used for forming capsules is preferably used to prepare capsules. Capsule-forming substances: (1) cellulose or cellulose; For the following types of substances that are not limited to cellulose, cellulose vinegar, and cellulose, including vitamins, and propylene: "Vinyl acetate, methyl cellulose, and ethyl cellulose propyl methyl fiber: Dimethyl methyl cellulose and phthalic acid are dilute = dimethyl ether T: ΐ Λ ^ methyl ^ acrylic acid methyl vinegar), poly (gasification, one spoonful of ethyl acetic acid i and not ^ ~ dimethyl Aminoacrylic acid fluorene. (3) Polyolefins: not limited to polyethylene, polypropylene, and polybutene. ⑷% vinyl such as 41 gas ethylene, polyvinyl acetate, polyvinyl alcohol, polystyrene, and propylene. Established month. In addition, polymers such as poly (2_ethyl_2 harmonica mouth sitting Lin) or alginic acid Page 10 200422162 V. Description of the invention (6) --- Salt can also be used to make capsules. Plasticizers used to shape the capsule-forming composition include, but are not limited to, glycerin, propylene glycol, polyethylene glycol (PEG 200-6000), diethyl phthalate, dibutyl phthalate, decyl Dibutyl Diacid, Tricitrate, Triethyl Acetate Citric Acid, Tributyl Acetate Citric Acid, & Tributyl Citrate S and coconut oil (preferably purified). The present invention also provides a hard capsule shell. The capsule hub includes a capsule forming composition composed of a polymer and a plasticizer, the polymer is not a gelatin material, and the capsule forming composition does not include any solvent. It can be divided into 0% to 40% by weight of the capsule forming composition, and Θ is better. ~ The preparation of hard shell plastic shells is as follows: the rubber shock forming group is i: the force is: open: and the shape is the capsule cap or the shell of the shell; the inner mold is heated, and a diameter smaller than the opening of the mold Grinding = forming group = temperature of the object's dazzling point; pressurization causes the heated heart pestle r to pull out the heated pestle: make the grind: the upper u dry; and remove it from the pestle to form the second glue =: Property? Finally, the present invention provides a method for preparing: the device comprises two main parts, respectively a ⑴ and η device. -One (1) mouth with the shape of the main body of the capsule cover or the shell of the capsule, which contains at least the shape of the research # Its shape is also a capsule or capsule shell, and the shape of the capsule is (the diameter of the sample is equal to the diameter of the sample to be prepared 200422162 of the capsule shell V. Description of the invention (7) Step j: Add the capsule forming composition into the mold first, and then dissolve: ΐ: ί 成 == 幵 7 pestle and heat to the pressure of the capsule forming composition so that the bismuth, # Λ 0 广 · # τ substance changed from Yang-like shape to liquid state); add & make the shiken pestle enter the pound branch, so that the compound is evenly coated and dried on the pestle ^ and remove it to get a hard capsule ^ Bladder molding, and the mold and pestle are preferably made of stainless steel. ‘2 Τ for drying kiln’ stomach kiln is suitable to keep above gelatin,: dagger: use temperature. When the capsule-forming composition is still on the pestle, the mixture is equal to the first two degrees. In addition, a pestle can be attached to an accelerated prayer. / Sleeve-out machine Each "capsule" as used in the present invention refers to a hard capsule (can be filled with medicament) containing a body and a lid. 2. Zhenzhi Capsule is mainly used to make non-gelatin capsules such as fiber; it is well developed, and generally used to make cellulose-based glue = J "Infusion coating method" Xiao method includes capping or glue: The method is called into a liquid solution containing a capsule composition. The capsule of the capsule body is immersed, and the innovative method of the present invention does not use "dipping, the main method is to use the capsule forming composition made of stainless steel = coating method", and the medium melting "hot melting method", the capsule in After being heated, it is coated on the pestle evenly, and it will be suitable for drying with stainless steel and removed from the pestle to obtain a shaped capsule shell. 'The “hot melt method” after drawing the mold away has the advantage that it does not need to contain a capsule forming group, and it is superior to other methods. The liquid solution patent method No. 2,5 2 6,6 8 3 of the second method of this method is disclosed by Murphy: Because it is not necessary to enter the solution by mistake every month as in the United States and to explain the matter with the invention, (8) set first Good speed extraction and removal ^^ Saves time and reduces costs. The composition of the plasticizer used in the gel of the present invention is the step of continuously heating the gelatinized capsule. In addition, the composition is composed of polymers and unnecessary additions. Wood coloring agents, pigments and other additives can also be considered to have a total of four main compositions, which are: (2) acrylic polyolefin. In addition, poly (or dimer, (3) ethylene polymer and (4) formulated in a capsule forming combination = f-2-oxazoline) or alginate can also be used or human Preparation: Vesuvial derivatives include natural nitric acid vinegar, cellulose triacetate, ortho fibers Element UPMc ") and o-benzene = HPC, HPMCP. The best cellulose polymer for white paper and propyl methylcellulose is white # 丝 π # based methylcellulose (HPMC) :: = vitamin (HPC) Glycyrrhizin-methyl acetate fiber acetate (CAP) and o-benzyl cellulose propyl methyl cellulose (HPMCp). Methylpropylmethylcellulose (UK National Formulary Booklet U) and o-benzyl 2D acetate (US Pharmacopoeia Book 18) are sometimes abbreviated as HPMC. O-phthalic acid is written as Mcp via propylphosphonium cellulose. Now f > 'There are two doses or forms of HPMCP available on the market from Tokyo, Japan. The two types of HpMcp were purchased by Vietnam Chemical Stock Injury Co., Ltd. Page 13 200422162 V. Description of the invention (9) HP-5 5. HP-5 0 has 20-25% fluorenyloxy, 8-12% hydroxypropyl, and 20-27% hydroxyphenyl. HP-55 has 18 to 22% methoxy, 6 to 10% hydroxypropyl, and 20 to 27 perphenyl. Both HP-50 and HP-55 dissolve in water in a test environment. HP-50 is dissolved when the pH is higher than 5, and HP-55 is dissolved when the pH is higher than 5.5. Compounds < polyacrylic acid, allyl alkenyl methacrylic acid methacrylic acid, or allyl polyacrylic acid ) Metriyl i-I acrylate, carboxylic acid, allylic acid, allylic acid, chloromethyl C-polyalkylene, polyisocyanate, polyethylenic acid, acrylic acid, acrylic acid Propylmethyl has allyl methacrylate and allylic acid: The structure of the methyl ester is as follows Page 14 200422162 V. Description of the invention (10) C—C. 2 Η C ο 3 Η C——C 2 Η · C ο CC 2 Η C ο ^ OH OR OH where R is a lower alkyl group such as methyl or Ethane. Methacrylic acid esters can be prepared according to many methods. Methacrylic acid / ester copolymers are also available in various dosages and forms. For example, Luo and Haas in Tokyo, Japan, and Eudragi tR series products containing various formulas of methyl acrylic acid / ester copolymers, such as EudragitR-E, L, S, RL, RS, NE. The above copolymers are almost all water-soluble in the test environment. Eu d r a g i t R series products suitable for the present invention are EudragitR-RS100 and RL-100. EudragitR L100 has a 1: 1 (methacrylic acid, methyl methacrylic acid) polymer and is sold in powder form. And EudragitR-S100 is Page 15 200422162 Polymers of (methacrylic acid, methyl methacrylate) with a ratio of 1: 2 are sold in the final form. EudragitR-L100-55 (methacrylic acid ', knife acid, ethacrylic acid) polymer with i: 1 is also sold in powder form. EudragitR-ElOO has 2 ·· 1 polymethyl methacrylate— (poly [methyl butyl methacrylate, (2-methylaminoamine ethyl) methacrylate, methyl methylpropionate]), with particles Form of sale. Eudragi tR-RL1 00 (ethyl acrylate, methyl methacrylate, trimethylamine chloride, ethyl acrylic acid methyl ester) polymer with a ratio of 1: 2: 0.2 is sold in the form of particles. EudragitR-RS100 is a 1: 2 ^ (ethyl acrylate, methyl methacrylate, vaporized trimethylamine ethyl acrylate) polymer and is also sold in pellet form. : F-based acrylate copolymers are anionic copolymers and are often used in intestinal release drugs because they are soluble only at pH values below 5.5. For example, the anionic copolymer EudragitR-S is soluble at a pH value of 7.0, EudragitR-s' or ^ is also soluble above 7.0, and EudragitR_RS is hardly soluble in water. Suitable ethylene polymers include, but are not limited to, polyethylene gas, polyvinyl acetate, polyvinyl alcohol, polystyrene, and polypropylene. Polyolefins include, but are not limited to, polyethylene hydrocarbons, polypropylene hydrocarbons, and polybutenes. In addition, the polymer in the capsule forming composition may be added as unnecessary Page 16 200422162 V. Plasticizer of the description of the invention (12). Suitable plasticizers include (1) polyethylene glycols such as polypropylene glycol, polybutylene glycol, and polyethylene glycol (PEG) (200-6000); (2) organic esters such as diethyl phthalate (DEP), Dibutyl phthalate (DBP), dibutyl sebacic acid (DBS); (3) citric acid such as citric acid triester (TEC), acetyl triethyl citric acid (ATEC), ethyl alcohol Base citric acid (ATBC), tributyl citrate (TBC) and glycerol triacetate (triacetin); (4) oils / glycerols such as sesame oil, ethyl alcohol monoglycerin and purified coconut oil. Suitable plasticizers are polyethylene glycols (such as PEG 100 and 400), trimethyl citrate, tributyl citrate, and triacetin. A suitable component of the plasticizer in the capsule-forming composition is 0 to 40% (by weight), and 0.001 to 20% is more suitable. [Embodiment] ^ The following examples are given as examples and are not intended to limit the scope of the present invention. [Example 1] The preparation steps of the hard capsule shell are as follows :) 65 'grams of hydroxypropyl cellulose (HPC) is added to a mold made of stainless steel with an opening, and the shape of the mold is a capsule cap Different sizes and sizes are required for the agent |, the inner diameter of the tungsten branch is equal to the capsule shell diameter; Page 17 200422162 V. Description of the invention (13) (2) The mold and the capsule forming pestle (also made of stainless steel) are heated to f6G C to completely resolve the HPC. The shape of the pestle can be a capsule cap or a body, and the The diameter is equal to the inner diameter of the capsule shell; 〆, 、, (3) When the HPC is still molten, pray the pestle so that the HPC can be evenly coated on the pestle; _ 俣 η plus & (4) Will the pestle Withdrawing from the mold, the extraction speed of the pestle can be used; the extraction of the funeral is accelerated (5), and the HPC coated on the pestle is dried, hardened and dried to complete gelation; ) Remove the HPC from the pestle. [Example 2] The preparation steps of the hard capsule shell are as follows: (1) Mixing about 65 mg of hydroxypropyl mg of PEG1_ (plasticizer component = 2 Jan) as a polymer; adding the bursal molding composition to the solution Heating the mold and the forming composition until 120t until Fan and Nawan (3) and the PM is still melted, pray the pestle into the mold, and pressurize so that the capsule capsule forming composition can be evenly coated on the pestle. Above; 200422162 V. Description of the invention (14) II) ::: Speed extraction from the mold 'can be accelerated by the connected extraction equipment 乂) The capsule molding composition coated on the pestle is dry Vo ",, Drying the capsule-forming composition to complete gelation. Version: 6) Remove the capsule-forming composition from the pestle. The size of the mold and pestle is the same as that described in the first embodiment. [Example 3] The steps for preparing a hard capsule shell are as follows: 嗣 RS100 (as a polymer) is dissolved in C == Λ * posted with _〇 and 0.7 mg of citron plasticizer) to prepare a capsule forming combination, and The capsule forming composition is heated to 501 to remove the acetone; the gel-like composition is added to a mold having an opening; (2) the mold and the capsule forming composition are heated to 120 ° C until Eu RS RS100 and TEC are completely melted; (3) When EudragitR RS100 and TEC are still melted, the pestle is prayed into the mold, and the pressure can be applied so that the capsule forming composition can be evenly coated on the pestle; (4) The pestle is withdrawn from the mold, which can be connected by Extraction equipment plus the extraction speed of the pestle;. Page 19, 200422162 V. Description of the invention (15) --- (5) The capsule forming composition coated on the pestle is dried and hardened, and the capsules are simmered during burning to make the capsules (6) Remove the capsule molding composition from the pestle. The size of the mold and pestle is as described in Example 1. [Example 4] u The hard capsule shell preparation steps are as follows: 2) 70 mg of EudragitR RU〇〇 (as a polymer) is dissolved in C = EudragitR RU 〇〇 ^^ butyl vinegar (tbc) (as a plasticizer) in acetone was mixed to prepare a capsule into a gram compound, and the capsule forming composition was added 埶 & 5. " Shape composition is added to the casting with openings; 5; to remove the Cgang; to win the capsule into (2) heating mold and capsule forming RL100 and TBC completely melt; material to 18 ° C until EudragtR (into) = ElTagitR RL10 When 0 and TBC are still dissolved, the pestle = extremely medium can be added to make the capsule forming composition evenly ground: in (4) the pestle is drawn from the mold, ^ ^ ^ ^ ^ ^ Extraction speed; the speed of JV is accelerated by the connected extraction equipment, and the capsule forming composition coated on the pestle is dried and hardened to complete the drying of the capsule forming composition; physical and chemical "hardening" can be found on page 20, 200422162, Description of the invention (16) (6) The capsule forming composition is removed from the pestle. The size of the prayer mold and the sample is the same as described in Example 1. [Example 5] The preparation steps of na I j hard capsule shell are as follows: ( 1) 70 mg as a polymer of $ 1 U mg of PEE. (As; =% by weight of the base and the capsule forming composition) 〇 ″ 约为 里 里 约 Composition · # 胶 # & Scoop 〇 / 〇) mixed to prepare a capsule shape: The molding composition is added to the heated mold with the opening (2) and the capsule forming fiber branch, and is completely melted; the material is reduced to ^ 00 C until HPMC and PEG (3) are still melted in HPMC and PEG. Capsule forming combination: Take out of the second research :: speed? Mold, can be connected to the research standard less than two (5) to coat the capsule molding composition to form the complete combination / dry hardening In (6), the capsule-forming composition can be removed from the pestle, [implementation :;], and the size of the pestle is the same as that described in Example-⑴ will be about 70 mg of poly (2_ Ethyl-2-oxoline) and 200422162 V. Description of the invention (17) As a plasticizer, about 7.8 mg of triacetin (TA) (the plasticizer component is 10% by weight of the gland sac forming composition) is mixed to prepare a capsule forming composition; The molding composition is added into a mold with an opening; (2) The surface mold and the capsule molding composition are heated to 120 until the poly (2 ~-2-卩 f 卩 sitting morpholine) and τ A are completely disintegrated; The compound can be evenly coated (3) in poly (2-ethyl-2_oxazoline) and TA or pestle into the mold, and the capsule forming group can be pressed on the pestle; (4) The extraction speed of the sample of the mortar pestle 1;-(5) The capsules formed by coating the capsules in a mortar and kneading mold and dried and hardened can be formed in "6." Gelatinization; the mold and the sample D are removed from the pestle. The above-mentioned meeting #, size is the same as the known examples of the first and second examples of ★, +, and Λ. The description is given by way of example, and is not intended to limit the present invention. Page 22 200422162 Brief description of the drawings on page 23 Abstract of the text (Invention name ·· Capsules of non-gelatin materials and preparation method thereof) The present invention provides a non-ming δ Hai method which is preferably a thermal fusion method. After heating in a mold, the molding composition was applied to a pestle, dried, and taken out from the pestle. Any solvent is used to dissolve the capsules and can be applied to the pestle under pressure when the pestle is inserted. The present invention also relates to a device for forming a hard capsule by forming a capsule from a plasticizer. The medicine of the glue material includes the capsule and the pestle. The method of applying the composition provided by the present invention on a pestle to make the capsule into a capsule provided by a polymer composition and a capsule forming group is better than the method of dipping the composition and preparing the preparation by preparing the compound The method of making the forming group more unnecessary because of not injecting the coating material. The powder-shaped subcapsule composition is hard to use, and the average amount of added medicinal ingredients is (1). The representative picture of this case is: ________ Figure_1b) Brief description of the component representative symbols of the representative figure in this case: Name · METH0D F0R MANUFAC ™ ^ The present invention provides a method for manufacturing a non-gelatin hard capsule shell · The hard capsule shell is made by a he, a t-me 11 i ng method which involves heating a capsule forming composition (preferably in powdery form) in a mold, foil owed by insert a pestle into the mold to coat the melted forming composition onto the pestle. The hard capsule thus formed, after 200422162 IV. Abstract of Chinese Invention (Invention Name: Capsule of Non-Gelatin Material and Preparation Method thereof) ) Lu and English Abstracts of Invention (Invention Name: METHOD FOR MANUFACTURING HARD NON-GELATIN PHARMACEUTICAL CAPSULES) hardened and dried, is removed from the pestle. This method has the conventional '丨 dip molding method " for not requiring the capsule, forming · composition to be preOd i sso1ved in solution so that no solvent is used in preparing the capsule forming composition. Also, by inserting a pestle into a mold, a pressure is imposed so as to ensure uniform coating of the capsule forming composition Page 3 200422162 IV. Abstract of Chinese Invention (Invention Name: Capsules of Non-Gelatin Material and Preparation Method) Abstract in Chinese and English (Invention Name: METHOD FOR MANUFACTURING HARD NON-GELATIN PHARMACEUTICAL CAPSULES) to the pestle. The present invention also provides a capsule forming composition which includes a polymer and optionally a plasticizer and an apparatus for making the non-gelatin hard capsule shell. Page 4 200422162 VI. Application Patent Scope [Shen Jing Patent Scope 1 · A non-gelatin moulding compound for the preparation of non-mingled capsules and combined capsule bodies; adding each die to the capsules will be supplemented by v # ,, Composition: The glue has been cooled and dried to form a combination 2. If the application is made of rust steel 3. If the application is made of cellulose 4. If the application is made of at least one ester, fiber cellulose, and o-phenylene 5 Dilute acid 6. For example, a method for applying a diameter-shaped combination of pestle capsules to form a dry mortar pestle self-developed patented gelatin material capsule, the method includes: adding at least / openings with a shape of a capsule cap or glue; the capsule forming The composition is composed of a polymer, and the mortar smaller than the opening diameter of the mold is heated to the melting point of the high temperature object; the pressure is pressed into the heated mold to contact the capsule forming composition; The gelled composition on the gelatin; and the dried capsule pestle is removed. According to the method described in item 1, the mold and pestle are prepared by the method described in item 1 of the non-patent scope, and the polymer is cellulose or biological. The patent is selected from the cellulose or cellulose derivatives described in the third scope of the patent scope of the patented biological patent of cellulose triacetate ethyl cellulose, vitamins, cellulose vinegar, cellulose, cellulose nitrate, o-benzene Cellulose diformate (CA P), methyl vitamins, hydroxypropyl cellulose, hydroxypropyl, methyl cellulose " depropylmethyl cellulose. The method described in the item "," or "item" is a polymer or copolymer. Enclosing acrylic or acrylic creatures as described in item 5 Page 24 200422162 Sixth, the scope of the patent application The polymer or copolymer is at least one selected from polyacrylic acid, polymethacrylic acid, poly (acrylic acid-methacrylic acid), poly (methyl acrylate-methyl methacrylate), poly (Ethyl acrylate-methyl methacrylate), poly (gasified ethyl acrylate-methyl methacrylate-trimethyl amino methacrylate polymer. 7 · As described in the first patent application scope Method, the polymer of which is a polyolefin, and at least one selected from the group consisting of polyethylene hydrocarbons, polypropylene hydrocarbons, and polybutenes. 8. The method according to item 1 of the patent application, wherein the polymer is an ethylene polymer and at least One is selected from the group consisting of polyvinyl chloride, polyvinyl acetate, polyvinyl alcohol, polystyrene, and polypropylene. 9. The method according to item 1 of the scope of patent application, wherein the polymer is poly (2-ethyl-2- Hire the forest) or alginate. 1 0. The method described in item 1 of the scope of patent application, the polymer is mixed with a plasticizer. 1 1. The plasticity described in item 10 of the scope of patent application At least one agent selected from the group consisting of polypropylene glycol, polybutylene glycol, and polyethylene glycol (PEG) (200-6000), diethyl phthalate, dibutyl phthalate, dibutylsebacate, triethyl citrate, acetotriethylcitrate, acetotributyl Based citric acid, tributyl citrate, glyceryl triacetate, castor oil, acetylated monoglyceride, and coconut oil. 1 2. A non-gelatin material capsule shell includes: > It consists of polymer and plasticizer Capsule-forming composition; The polymer is not gelatin, and the above-mentioned capsule-forming group does not include a solvent; the plasticizer component is about 0 to 40% by weight of the capsule-forming composition. Page 25 200422162 VI. Application for patent scope 13. If the patent application scope item 12 adds the capsule forming composition to at least / of ^ month knee material capsule shell, it is the mold of the main body of the f capsule. The mold and: To win the sigh of sigh or heat to the sac of the sac, the combination point 1 has been added 2 = 2, the pestle has been added with # fr Α π contact capsule forming composition; the heated and Dosang e Shun capsule is formed, and the person :: "Panel draw-off; cool and dry the pestle on the pestle. ~, The dried capsule forming composition is moved from the pestle to the application of the non-gelatin material capsule shell as described in item 12 of the scope, which Cellulose, cellulose vinegar, cellulose ether, fiber: acid; at least one species; esters, o-jasmine-Tianshiluyue® Bunting purpose, fiber triacetate_cellulose, propylmethylcellulose ethyl Cellulose field-based cellulose. Τ ㈤ hydroxypropyl dicarboxylate · 15. The polymer made of non-gelatin as described in item 2 of the patent application scope is acrylic acid or acrylic acid derivative: capsule shell 1, and At least-a species selected from the polypropylene " methyl 1 copolymerization (co-methyl methacrylic acid), poly ( Acrylic acid acrylic acid ~ methyl acrylic green =, ethyl acrylic acid (ethyl acrylate-methyl methyl acrylate), poly (chlorine: methyl acrylic acid) ^ purpose ~ trimethyl amino methacrylate . Sour ethyl alcohol, its polypropylene, which is the non-gelatin material structure as described in the application scope of the patent, the polymer is a hydrocarbon, the truth is small-species selection, >, olefin and polybutene Header 1% hydrocarbons, 17 · Capsule shells of non-gelatin materials as described in item 12 of the scope of patent application Page 26 200422162 Sixth, the scope of the patent application The composition of the polymer is ethylene polymer, and at least one kind is selected from polyvinyl chloride, polyvinyl acetate, polyvinyl alcohol, polystyrene and polypropylene. 18. The capsule shell of a non-gelatin material as described in the scope of the patent application No. 丨 2 顼, the composition of which is poly (2-ethyl-2-oxaxline) or aginate. 19 ·· The capsule shell of non-gelatin material as described in item 12 of the scope of patent application, the plasticizer is at least one kind selected from polydiethylene glycol, polybutylene glycol, and polyethylene glycol (PEG) (2〇〇 -600), diethyl phthalate, dibutyl phthalate L ^ butyl sebacic acid, triethyl citrate, ethyl triethyl citrate, 3 Γ: ? Citric acid, tributyl citrate, 2 glyceryl acetate, castor oil acetylated monoglyceride and gardenia oil. 20. The capsule shell of a non-gelatin material as described in item 2 of the scope of the patent application, the speed of the plasticizer component is about 20% of the weight percentage of the capsule forming combination. · 21 · —A kind of capsule used for preparing capsule shells made of non-gelatin materials. 5 J, head and ham. Li Wang Shao has an opening and is in the shape of a capsule. 'First, the pestle with a diameter smaller than the opening of the mold mentioned above, the grinding into the S fork, the pestle and the mold are heated to be higher than the glue ^, π: "After that, the pestle prays to the mold to be fine", After dissolution, it is drawn out from the mold. / Capsule forming composition connection 2 2 · The device described in item 2 丨 of the patent application scope is made of stainless steel. Both the μ caster and the pestle 23. The device described in item 12 of the scope of the patent application is used to accelerate the curing and drying of the rubber molding composition on the pestle. ΙΗ p. 27 200422162 Page 28