CN105663107A - Compound amino acid capsule - Google Patents

Compound amino acid capsule Download PDF

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Publication number
CN105663107A
CN105663107A CN201610060208.1A CN201610060208A CN105663107A CN 105663107 A CN105663107 A CN 105663107A CN 201610060208 A CN201610060208 A CN 201610060208A CN 105663107 A CN105663107 A CN 105663107A
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vitamin
capsule
methionine
grain
weighting material
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CN105663107B (en
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李兴惠
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/606—Salicylic acid; Derivatives thereof having amino groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • 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
    • A61K9/4866—Organic macromolecular compounds

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention relates to a compound amino acid capsule. The compound amino acid capsule comprises a capsule shell and powdery or granular filler wrapped in the capsule shell, wherein the capsule shell is a hollow gelatin capsule prepared from gelatin as a main component; the filler comprises active substances and pharmaceutic adjuvants. The compound amino acid capsule adopts a scientific and reasonable ratio, has good product stability, is free of toxic and side effects, has high safety and good biological effect, and can be applied to preparation of drugs for treating chronic liver and kidney diseases and food for relieving and eliminating physical fatigue caused by exercise training. The capsule has the characteristics superior to those in the prior art.

Description

Compound amino acid capsule agent
Technical field
The present invention relates to a kind of capsule medicament and preparation method thereof, specifically, relate to a kind of comprise 8 seed amino acids and the capsule of 11 kinds of vitamin micro pills, also can be called and compound amino acid capsule also relate to the preparation method of this capsule.
Background technology
Protein is the basic substance of human life activity, the repairing effect of human body every physiological function, particularly immunologic function, cell injury and function of growing, and whether normal with its metabolism has extremely close relationship. Under normal circumstances, human body obtains each seed amino acid by the protein in food to ensure the normal of body protein metabolism. In 20 seed amino acids required for human body protein synthesis, wherein having 8 seed amino acids to be essential amino acid, this 8 seed amino acid itself can not synthesize and must depend on external supply in body. They are Isoleucine, leucine, Methionin, phenylalanine, Threonine, α-amino-isovaleric acid, methionine(Met) and tryptophane. For protein synthesis, this 8 seed amino acid is indispensable, and all can affect the synthesis of protein when content is not enough or proportioning is unbalanced.
In the process of the generation of disease, development and recovery from illness; due to various pathology and stress reaction; in addition improper diet or tract function is affected; usually there will be the disorder of protein metabolism, and the death that the disorder of protein metabolism often causes with disease, the generation of complication and the time length of disease are closely related. In clinical practice, therefore, the supply of nitrogen matter is treatment means indispensable, effective.
From World War II, the U.S. takes the lead in releasing protolysate, for the supply of nitrogen matter in disease process. The fifties, Japan achieves amino acid whose large scale fermentation and purification, ensures for crystal type amino acid transfusion provides favourable technology. Entering for the 's, 80, amino acid transfusion is constantly the treatment of clinical all kinds of acute disease, seriously disease, particularly to urgent patient and through the ingest treatment of patient of mouth, strong support can not be provided.
But the treatment for chronic disease, the treatment of the patient that particularly can ingest through mouth, the limitation of amino acid transfusion is obviously. From the feature of vivo acid metabolism, amino acid transfusion may cause that vivo acid proportioning is not normal, in infusion process serum amino acid excessive concentration, transfusion stop after serum amino acid concentration rapid decrease, the row's nitrogen burden that increases the weight of liver, the untoward reaction that simultaneously likely causes infusion reaction, vein blood vessel scorching etc. What is more important amino acid transfusion only has the effect promoting positive nitrogen balance in short, and life-time service result for the treatment of is not obvious.
Just because of this, while parenteral nutrition develops, development abroad the perfect multiple enteral nutrition preparation being made up of nitrogenous sources such as crystalline aminoacid, protolysate, complete proteins. Enteral nutrition preparation is mainly taken in through mouth, required nutrient substance is provided to meet the needs of body metabolism, enteral nutrition is conducive to keeping the integrity of enteron aisle structure and function compared with parenteral nutrition, prevent the intestinal mucosa atrophy caused by long-term parenteral nutrition and bacterium displacement, be conducive to improving the immunizing power of body.
At present, paying much attention to the treatment of enteral nutrition in domestic and international clinical practice, particularly in the long-term treatment of chronic disease, the ratio of enteral nutrition treatment greatly exceed the treatment of parenteral nutrition. As long as " gastrointestinal function allows, and adopts enteral nutrition " is the principle of clinic nutrition treatment as far as possible. Therefore, people are badly in need of solving the medicine for intestinal feeding treatment. Owing to amino acid is unstable, causes Amino Acid Oral Preparation product stability poor, govern the application of Amino Acid Oral Preparation product. For this reason, those skilled in the art attempt the new preparation comprising amino acid and VITAMIN of exploitation and successfully they are pushed to clinical.
Chinese Patent Application No. 021586195 (ten thousand Hes, CN1424027A) relates to a kind of composite amino acid capsule and its preparation method. This invention product comprises the multiple supplementary material such as 8 seed amino acids, 11 kinds of VITAMIN composition, concrete formula and preparation method, this invention product advantage is: reasonable ratio, science, have good biological effect, technique is unique, advanced, convenient oral, having no side effect, security height, obtains doctor and patient welcomes. Product of the present invention is used for chronic liver, kidney and other disease treatment.
Chinese Patent Application No. 200410100003.9 (holy and, CN1781486A) a kind of compound amino acid and vitamine capsule preparation is disclosed, it comprises amino acid coated granule and VITAMIN coated granule, wherein the weight ratio of amino acid coated granule and VITAMIN coated granule is 1: 0.68, wherein said amino acid coated granule comprises Isoleucine, leucine, lysine hydrochloride, phenylalanine, methionine(Met), Threonine, tryptophane, α-amino-isovaleric acid, and arginine hydrochloride, described VITAMIN coated granule comprises vitamin b1 nitrate, Lin Suanna Vitamin B2 Sodium Phosphate, vitamin B6, Vitamin E acetate and niacinamide. this invention additionally provides prepares the method for compound amino acid with vitamine capsule preparation.
Chinese Patent Application No. 200910153422.1 (Sai Li, CN102038691A) discloses a kind of VITAMIN amino acid composite preparation, carries out dressing by vitamin complex and aminoacids complex and is prepared into micro-ball and obtains. It is believed that the VITAMIN amino acid composite preparation of this invention gained, be compounded with multivitamin and amino acid easy to use, adopt micro-ball sustained release coating technology to improve bioavailability, steady quality, absorption of human body is fast.
Chinese Patent Application No. 201010102505.0 (ten thousand Hes, CN101773512A) a kind of 8 seed amino acids and 11 kinds of vitamin micro pill capsules and its preparation method is disclosed, comprising 7 kinds of microspheric granulas, described 7 kinds of microspheric granulas are made up of the raw material of following weight part: 2.66～9.9 parts, the micro-ball of thiamine mononitrate, vitamin micro pill a16.35～20.5 part, amino acid micro-ball a35.0～44.1 part, vitamin micro pill b11.4～14.4 part, amino acid micro-ball b6.65～10.5, vitamin C micro-pill 12.73～16.0 parts, 5.7～9.36 parts, the micro-pearl of vitamin AD.This invention proportioning science, rationally, the good stability of product, have no side effect, security height, has good biological effect, it is possible to be applied in preparation treatment chronic liver, kidney diaseases medicine, alleviates and eliminates in training muscle power fatigue food.
Chinese Patent Application No. 201310055941.0 (ten thousand Hes, CN103142633A) discloses a kind of compound amino acid capsule (8-11) and its preparation method. Specifically, it relates to a kind of comprise 8 seed amino acids and the capsule of 11 kinds of vitamin micro pills, the preparation method of this capsule is also related to. This capsule comprises 7 kinds of microspheric granulas, and described 7 kinds of microspheric granulas are made up of the raw material of following weight part: 2.66～9.9 parts, the micro-ball of thiamine mononitrate, vitamin micro pill a16.35～20.5 part, amino acid micro-ball a35.0～44.1 part, vitamin micro pill b11.4～14.4 part, amino acid micro-ball b6.65～10.5, vitamin C micro-pill 12.73～16.0 parts, 5.7～9.36 parts, the micro-pearl of vitamin AD. It is believed that this invention proportioning science, rationally, the good stability of product, have no side effect, security height, has good biological effect, it is possible to be applied in preparation treatment chronic liver, kidney diaseases medicine, alleviates and eliminates in training muscle power fatigue food. It is believed that this invention capsule has the advantages that to be better than prior art.
Regrettable, above-mentioned prior art, when preparing the preparation comprising 8 seed amino acids and 11 kinds of VITAMIN, is all that amino acid and/or VITAMIN are made piller, then by its dressing, is then divided in empty hard capsule shell by coated pellets. The encapsulated technique of the powder/granule in routine of this kind of preparation process ratio has significantly higher production cost, and this kind of production cost brings huge medical burden by for patient person's medication.
Therefore, develop a kind of drug standard that meet to require and compound amino acid capsule that production technique simply comprises 8 seed amino acids and 11 kinds of VITAMIN is that those skilled in the art extremely expect.
Summary of the invention
The goal of the invention of the present invention is to provide and a kind of contains 8 seed amino acids and the capsule of 11 kinds of VITAMIN, expects that this kind of capsule has production technique simple and have the feature of excellent pharmacy quality. The present invention has been surprisingly found that, it may also be useful to the capsule containing 8 seed amino acids and 11 kinds of VITAMIN that the inventive method prepares can realize above-mentioned purpose completely. The present invention finds based on this and is accomplished.
In the present invention, described capsule refers to the known hard capsule of art of pharmacy, to be different from the soft capsule that people know usually. The weighting material that hard capsule typically comprises capsule shell (being usually also called Capsules) and is wrapped in this capsule shell, described weighting material is powder or particulate state usually, the pharmaceutical excipient wherein comprising active constituents of medicine and adding if desired. Pharmaceutical field technician's public affairs are known, for capsule particularly hard capsule, the above-mentioned weighting material that its capsule shell inside is filled, is also called " content ". On the invention, hereafter in each embodiment, the various weighting materials prepared are filled in the Capsules of suitable size, make described content substantially be full of capsule body, then are sealed by capsule cap fit.
In a first aspect of the present invention, it provides a kind of capsule, in it comprises capsule shell and is wrapped in this capsule shell and in powder or the weighting material of particulate state; Described capsule shell take gelatin as the gelatin hollow capsule that main ingredient is made, and described weighting material comprises active substance and pharmaceutical excipient; Described active substance comprises:
Capsule according to the present invention, its each grain comprises the amount of active substance and is:
L-Leu 14.5～22mg ILE 4.5～7mg
LYS 20～30mg L-Phe 4～6mg
L-threonine 3.3～5mg Valine 5.3～8mg
L-Trp 4～6mg Such as, methionine(Met) (L-Methionine or DL-methionine) 14.5～22mg
Vitamin A 1600～2400IU Vitamin D2 160～240IU
VITMAIN B1 (or sulfuric acid thiamine) 4～6mg Lin Suanna Vitamin B2 Sodium Phosphate 2.4～3.6mg
Niacinamide 1.6～25mg Vitamin B6 2～3mg
Folic acid 0.16～0.24mg Calcium pantothenate 4～6mg
Vitamin B12 0.8～1.2ug Vitamins C 16～24mg
Vitamin-E 0.8～1.2mg 5-hydroxyl anthranilic acid hydrochloride 0.16～0.24mg
Capsule according to the present invention, its each grain comprises the amount of active substance and is:
L-Leu 16.5～20mg ILE 5.3～6.5mg
LYS 22.5～27.5mg L-Phe 4.5～5.5mg
L-threonine 3.7～4.6mg Valine 6～7.5mg
L-Trp 4.5～5.5mg Such as, methionine(Met) (L-Methionine or DL-methionine) 16.5～20mg
Vitamin A 1800～2200IU Vitamin D2 180～220IU
VITMAIN B1 (or sulfuric acid thiamine) 4.5～5.5mg Lin Suanna Vitamin B2 Sodium Phosphate 2.7～3.3mg
Niacinamide 1.8～22mg Vitamin B6 2.25～2.75mg
Folic acid 0.18～0.22mg Calcium pantothenate 4.5～5.5mg 3-->
Vitamin B12 0.9～1.1ug Vitamins C 18～22mg
Vitamin-E 0.9～1.1mg 5-hydroxyl anthranilic acid hydrochloride 0.18～0.22mg
Capsule according to the present invention, the amount that its each grain comprises active substance is about:
L-Leu 18.3mg ILE 5.9mg
LYS 25mg L-Phe 5mg
L-threonine 4.2mg Valine 6.7mg
L-Trp 5mg Such as, methionine(Met) (L-Methionine or DL-methionine) 18.4mg
Vitamin A 2000IU Vitamin D2 200IU
VITMAIN B1 (or sulfuric acid thiamine) 5mg Lin Suanna Vitamin B2 Sodium Phosphate 3mg
Niacinamide 2mg (or 20mg) Vitamin B6 2.5mg
Folic acid 0.2mg Calcium pantothenate 5mg
Vitamin B12 1ug Vitamins C 20mg
Vitamin-E 1mg 5-hydroxyl anthranilic acid hydrochloride 0.2mg
Capsule according to the present invention, wherein said pharmaceutical excipient is selected from following one or more: lactose, starch, Microcrystalline Cellulose, dextrin, sucrose, Magnesium Stearate, Vltra tears, carboxymethyl starch, sodium starch glycolate, methylcellulose gum, ethyl cellulose etc.
Capsule according to the present invention, the pharmaceutical excipient total amount comprised in its each grain is 80～400mg.
Capsule according to the present invention, the pharmaceutical excipient total amount comprised in its each grain is 100～350mg.
Capsule according to the present invention, the pharmaceutical excipient total amount comprised in its each grain is 100～300mg.
Capsule according to the present invention, wherein said pharmaceutical excipient comprises: starch and Magnesium Stearate.
Capsule according to the present invention, the amount of starch comprised in its each grain is 80～350mg.
Capsule according to the present invention, the amount of starch comprised in its each grain is 100～300mg.
Capsule according to the present invention, the amount of starch comprised in its each grain is 100～250mg.
Capsule according to the present invention, the Magnesium Stearate comprised in its each grain accounts for the 0.2～10% of described weighting material weight.
Capsule according to the present invention, the Magnesium Stearate comprised in its each grain accounts for the 0.5～5% of described weighting material weight.
Capsule according to the present invention, the Magnesium Stearate comprised in its each grain accounts for the 0.5～3% of described weighting material weight.
Capsule according to the present invention, the weight of the weighting material comprised in its each grain is 200～500mg.
Capsule according to the present invention, the weight of the weighting material comprised in its each grain is 225～450mg.
Capsule according to the present invention, the weight of the weighting material comprised in its each grain is 250～400mg.
Capsule according to the present invention, the granularity of its weighting material is: the particle of more than 99% sieves by 20 orders.
Capsule according to the present invention, the granularity of its weighting material is: the particle of more than 99% sieves by 24 orders.
Capsule according to the present invention, the granularity of its weighting material is: the particle of more than 95% sieves by 50 orders.
Capsule according to the present invention, the granularity of its weighting material is: the particle of more than 90% sieves by 65 orders.
Capsule according to the present invention, it is that the method by comprising the following steps prepares:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Can by even for each for the present invention mixing of materials by well-mixed technique. certainly, in order to improve mixing efficiency, also can by several components little for consumption, such as vitamin A, vitamin D2, folic acid, vitamin B12, vitamin-E, 5-hydroxyl anthranilic acid hydrochloride etc. are mixed outstanding with ethanol, it is sprayed in part or all of rest activity material and/or pharmaceutical excipient again, after solvent to be removed, mix with the active substance of surplus and/or pharmaceutical excipient. the present inventor is found by checking, different blending meanss except to mixture homogeneity ageing variant except, (whole capsules that hereafter each embodiment is obtained when content various in every capsules reaches calculating formula A+1.45S≤15.0 (Chinese Pharmacopoeia version in 2010 two the annex XE institute support methods) of uniformity of dosage units lower than the/active substance that equals 5mg, wherein various content lower than A+1.45S through calculating them of/active substance that equals 5mg all in 6.2～12.5 scopes), the capsule that these different mixing modes obtain does not demonstrate difference in stability test of the present invention detects, namely different mixing modes to the stability of product and has no significant effect.
Further, second aspect present invention provides the method preparing capsule, and described capsule comprises capsule shell and is wrapped in this capsule shell and in powder or the weighting material of particulate state; Described capsule shell take gelatin as the gelatin hollow capsule that main ingredient is made, and described weighting material comprises active substance and pharmaceutical excipient; Described active substance comprises:
L-Leu ILE
LYS L-Phe
L-threonine Valine
L-Trp Such as, methionine(Met) (L-Methionine or DL-methionine)
Vitamin A Vitamin D2
VITMAIN B1 (or sulfuric acid thiamine) Lin Suanna Vitamin B2 Sodium Phosphate
Niacinamide Vitamin B6
Folic acid Calcium pantothenate
Vitamin B12 Vitamins C
Vitamin-E 5-hydroxyl anthranilic acid hydrochloride;
The method comprises the following steps:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Method according to the present invention, each grain of described capsule comprises the amount of active substance and is:
L-Leu 14.5～22mg ILE 4.5～7mg
LYS 20～30mg L-Phe 4～6mg
L-threonine 3.3～5mg Valine 5.3～8mg
L-Trp 4～6mg Such as, methionine(Met) (L-Methionine or DL-methionine) 14.5～22mg
Vitamin A 1600～2400IU Vitamin D2 160～240IU
VITMAIN B1 (or sulfuric acid thiamine) 4～6mg Lin Suanna Vitamin B2 Sodium Phosphate 2.4～3.6mg
Niacinamide 1.6～25mg Vitamin B6 2～3mg
Folic acid 0.16～0.24mg Calcium pantothenate 4～6mg
Vitamin B12 0.8～1.2ug Vitamins C 16～24mg
Vitamin-E 0.8～1.2mg 5-hydroxyl anthranilic acid hydrochloride 0.16～0.24mg
Method according to the present invention, each grain of described capsule comprises the amount of active substance and is:
L-Leu 16.5～20mg ILE 5.3～6.5mg
LYS 22.5～27.5mg L-Phe 4.5～5.5mg
L-threonine 3.7～4.6mg Valine 6～7.5mg
L-Trp 4.5～5.5mg Such as, methionine(Met) (L-Methionine or DL-methionine) 16.5～20mg
Vitamin A 1800～2200IU Vitamin D2 180～220IU
VITMAIN B1 (or sulfuric acid thiamine) 4.5～5.5mg Lin Suanna Vitamin B2 Sodium Phosphate 2.7～3.3mg
Niacinamide 1.8～22mg Vitamin B6 2.25～2.75mg
Folic acid 0.18～0.22mg Calcium pantothenate 4.5～5.5mg
Vitamin B12 0.9～1.1ug Vitamins C 18～22mg
Vitamin-E 0.9～1.1mg 5-hydroxyl anthranilic acid hydrochloride 0.18～0.22mg
Method according to the present invention, the amount that each grain of described capsule comprises active substance is about:
Method according to the present invention, wherein said pharmaceutical excipient is selected from following one or more: lactose, starch, Microcrystalline Cellulose, dextrin, sucrose, Magnesium Stearate, Vltra tears, carboxymethyl starch, sodium starch glycolate, methylcellulose gum, ethyl cellulose etc.
Method according to the present invention, the pharmaceutical excipient total amount comprised in each grain of described capsule is 80～400mg.
Method according to the present invention, the pharmaceutical excipient total amount comprised in each grain of described capsule is 100～350mg.
Method according to the present invention, the pharmaceutical excipient total amount comprised in each grain of described capsule is 100～300mg.
Method according to the present invention, the pharmaceutical excipient described in described capsule comprises: starch and Magnesium Stearate.
Method according to the present invention, the amount of starch comprised in each grain of described capsule is 80～350mg.
Method according to the present invention, the amount of starch comprised in each grain of described capsule is 100～300mg.
Method according to the present invention, the amount of starch comprised in each grain of described capsule is 100～250mg.
Method according to the present invention, the Magnesium Stearate comprised in each grain of described capsule accounts for the 0.2～10% of described weighting material weight.
Method according to the present invention, the Magnesium Stearate comprised in each grain of described capsule accounts for the 0.5～5% of described weighting material weight.
Method according to the present invention, the Magnesium Stearate comprised in each grain of described capsule accounts for the 0.5～3% of described weighting material weight.
Method according to the present invention, the weight of the weighting material comprised in each grain of described capsule is 200～500mg.
Method according to the present invention, the weight of the weighting material comprised in each grain of described capsule is 225～450mg.
Method according to the present invention, the weight of the weighting material comprised in each grain of described capsule is 250～400mg.
Method according to the present invention, the granularity of described capsule weighting material is: the particle of more than 99% sieves by 20 orders.
Method according to the present invention, the granularity of described capsule weighting material is: the particle of more than 99% sieves by 24 orders.
Method according to the present invention, the granularity of described capsule weighting material is: the particle of more than 95% sieves by 50 orders.
Method according to the present invention, the granularity of described capsule weighting material is: the particle of more than 90% sieves by 65 orders.
Method according to the present invention, wherein vitamin A, vitamin D2, folic acid, vitamin B12, vitamin-E, 5-hydroxyl anthranilic acid hydrochloride etc. mix to hang with ethanol and are sprayed in part or all of rest activity material and/or pharmaceutical excipient again, after solvent to be removed, mix with the active substance of surplus and/or pharmaceutical excipient, make mixed powder eventually.
The gelatin hollow capsule that the present invention relates to typically has recorded version " Chinese Pharmacopoeia " two in 2010, and there are many products by the approval listing of state food pharmaceuticals administration general bureau, the gelatin hollow capsule of such as traditional Chinese medicines accurate word F20020009 (Renhe, Shaoxing), traditional Chinese medicines accurate word F20020035 (Zhejiang enlightening is raw) and traditional Chinese medicines accurate word F20030004 (the long standing grain in Jiangsu).
Capsule according to the present invention, it is that the directly encapsulated mode of powder prepares.
A kind of 8 seed amino acids of the present invention and 11 kinds of vitamin micro pill capsules are in preparation treatment chronic liver, kidney diaseases medicine, alleviation and the application eliminated in training muscle power fatigue food.
When chronic hepatic diseases, cell can be effectively improved to amino acid whose bioavailability on the basis not increasing patient's nitrogen matter excretion burden, 8 seed amino acids of the biosynthesizing of promotion protein and 11 kinds of vitamine capsule technique uniquenesses, advanced technology, validity period were more than 3 years, product of the present invention is used for chronic liver, kidney and other disease treatment, alleviates and eliminates muscle power fatigue.
The present invention, as the enteral nutrition preparation improving nitrogenous source amino acid composition, has outstanding advantage in chronic disease therapy. First, it does not need the dietary structure and other treatment plans that change patient, just can significantly improve amino acid and the protein metabolism of patient; Secondly, when chronic hepatic diseases, it can effectively improve cell to amino acid whose bioavailability on the basis not increasing patient's nitrogen matter excretion burden, promotes the biosynthesizing of protein. The present invention is compared with existing amino acid product technology, and tool has the following advantages:
1. reasonable ratio, science, there is good biological effect. The amino acid preparation that it is different and general, the ratio of its 8 kinds of indispensable amino acids combines Asian-Pacific area dietary protein structure, amino acid composition and the many-sided combined factors of absorption of human body and considers to determine, the wherein large percentage of branched-chain amino acid, Methionin, methionine(Met), add 11 kinds of VITAMIN simultaneously, give full play to the synergy of amino acid and VITAMIN, make amino acid balanced absorption in human body, ensure amino acid whose bioavailability.
2. technique is unique, advanced, solve the shortcoming of other Moriamin Forte preparations, 8 kinds of indispensable amino acids and the mixing of 11 kinds of VITAMIN can be ensured can not occur in storage period between each composition chemical reaction and degraded, it is to increase the stability of various activeconstituents in product.
3. convenient oral. Moriamin Forte preparation needs in the treatment of amino acid preparation chronic disease patient for a long time, it is possible to make up some deficiency of amino acid transfusion. The present invention is more suitable for the chronic disease patient for Long-term taking medicine, has both alleviated patient economy burden, which in turn improves the psychological bearing capability of patient simultaneously.
The capsule that various embodiments of the present invention prepare, it stays sample at ambient temperature for a long time, respectively at sampling in 0,3,6,9,12,18,24,36 month, by hereafter contained method, in conjunction with version Chinese Pharmacopoeia in 2010 two measuring methods recorded, the sample of different time is measured every index. Result shows, various embodiments of the present invention stay the sample of sample for 0 month to 36 months, the content of 8 seed amino acids remains in 93～105% scopes of labelled amount respectively within the time period of 3 years, the content of 11 kinds of VITAMIN remains on respectively in 95～105% scopes of labelled amount within the time period of 3 years, shows capsule of the present invention and meets drug standard requirement completely.
Embodiment
The following examples are used for illustrating further the present invention, but this and do not mean that any limitation of the invention. In following test, during preparation capsule of the present invention, every batch is prepared in the batch of capsule number at least 2 ten thousand amount, but when listing formula, all indicates with the amount of every. In following test, during preparation capsule of the present invention, if not otherwise indicated, the granularity of capsule weighting material is: the particle of more than 95% sieves by 50 orders. In following test, during preparation capsule of the present invention, if not otherwise indicated, Capsules used is gelatin hollow capsule.
Embodiment 1: prepare capsule
Formula:
L-Leu 18.3mg ILE 5.9mg
LYS 25mg L-Phe 5mg
L-threonine 4.2mg Valine 6.7mg
L-Trp 5mg DL-methionine 18.4mg
Vitamin A 2000IU Vitamin D2 200IU
VITMAIN B1 5mg Lin Suanna Vitamin B2 Sodium Phosphate 3mg
Niacinamide 2mg Vitamin B6 2.5mg
Folic acid 0.2mg Calcium pantothenate 5mg
Vitamin B12 1ug Vitamins C 20mg
Vitamin-E 1mg 5-hydroxyl anthranilic acid hydrochloride 0.2mg
Starch 170mg Magnesium Stearate * 2%
Note: * Magnesium Stearate throws material with the per-cent of capsule filling gross weight, lower same.
Method for making 1:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Method for making 2:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) outstanding it is sprayed in the starch of 1/3 amount again by mixed to vitamin A, vitamin D2, folic acid, vitamin B12, vitamin-E, 5-hydroxyl anthranilic acid hydrochloride ethanol 3 times of these 6 kinds of active material gross weights (consumption be), to be dried except after desolventizing, mix with the active substance of surplus and/or pharmaceutical excipient, make mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
By the obtained two batches of capsules of above two kinds of methods. All refer to method for making 1 gained capsule when hereafter each test example relating to embodiment 1 sample or it is prepared according to method for making 1; But method for making 1 and method for making 2 two kinds of capsule no significant differences in each test example.
The gelatin hollow capsule that the present embodiment uses is F20020009, when hereafter not illustrating in addition, also uses this Capsules
Embodiment 2: prepare capsule
Formula:
Method for making:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder (its granularity is: the particle of more than 90% sieves) eventually by 65 orders;
(iii) being filled in hard capsule case (F20020035) by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Embodiment 3: prepare capsule
Formula:
L-Leu 14.5mg ILE 4.5mg
LYS 30mg L-Phe 6mg
L-threonine 3.3mg Valine 5.3mg
L-Trp 6mg DL-methionine 22mg
Vitamin A 1600IU Vitamin D2 160IU
VITMAIN B1 6mg Lin Suanna Vitamin B2 Sodium Phosphate 2.4mg
Niacinamide 1.6mg Vitamin B6 3mg
Folic acid 0.24mg Calcium pantothenate 4mg
Vitamin B12 0.8ug Vitamins C 24mg
Vitamin-E 1.2mg 5-hydroxyl anthranilic acid hydrochloride 0.16mg
Starch 100mg Magnesium Stearate 5%
Method for making:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder (its granularity is: the particle of more than 95% sieves) eventually by 65 orders;
(iii) being filled in hard capsule case (F20030004) by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Embodiment 4: prepare capsule
Formula:
L-Leu 22mg ILE 7mg
LYS 20mg L-Phe 4mg
L-threonine 5mg Valine 8mg
L-Trp 4mg DL-methionine 14.5mg
Vitamin A 2400IU Vitamin D2 240IU
VITMAIN B1 4mg Lin Suanna Vitamin B2 Sodium Phosphate 3.6mg
Niacinamide 2.4mg Vitamin B6 2mg
Folic acid 0.16mg Calcium pantothenate 6mg
Vitamin B12 1.2ug Vitamins C 16mg
Vitamin-E 0.8mg 5-hydroxyl anthranilic acid hydrochloride 0.24mg
Starch 200mg Magnesium Stearate 0.2%
Method for making:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Embodiment 5: prepare capsule
Formula:
L-Leu 16.5mg ILE 5.3mg
LYS 27.5mg L-Phe 5.5mg
L-threonine 3.7mg Valine 6mg
L-Trp 5.5mg DL-methionine 20mg
Vitamin A 1800IU Vitamin D2 180IU
VITMAIN B1 5.5mg Lin Suanna Vitamin B2 Sodium Phosphate 3.3mg
Niacinamide 1.8mg Vitamin B6 2.25mg
Folic acid 0.22mg Calcium pantothenate 5.5mg
Vitamin B12 0.9ug Vitamins C 18mg
Vitamin-E 1.1mg 5-hydroxyl anthranilic acid hydrochloride 0.22mg
Starch 250mg Magnesium Stearate 5%
Method for making:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Embodiment 6: prepare capsule
Formula:
L-Leu 20mg ILE 6.5mg
LYS 22.5mg L-Phe 4.5mg 10 -->
L-threonine 4.6mg Valine 7.5mg
L-Trp 4.5mg DL-methionine 16.5mg
Vitamin A 2200IU Vitamin D2 220IU
VITMAIN B1 4.5mg Lin Suanna Vitamin B2 Sodium Phosphate 2.7mg
Niacinamide 2.2mg Vitamin B6 2.75mg
Folic acid 0.18mg Calcium pantothenate 4.5mg
Vitamin B12 1.1ug Vitamins C 22mg
Vitamin-E 0.9mg 5-hydroxyl anthranilic acid hydrochloride 0.18mg
Starch 150mg Magnesium Stearate 10%
Method for making:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Embodiment 7: prepare capsule
Formula:
L-Leu 14.5mg ILE 7mg
LYS 30mg L-Phe 4mg
L-threonine 3.3mg Valine 8mg
L-Trp 6mg L-Methionine 14.5mg
Vitamin A 1600IU Vitamin D2 240IU
Sulfuric acid thiamine 6mg Lin Suanna Vitamin B2 Sodium Phosphate 2.4mg
Niacinamide 16mg Vitamin B6 3mg
Folic acid 0.24mg Calcium pantothenate 4mg
Vitamin B12 0.8ug Vitamins C 24mg
Vitamin-E 1.2mg 5-hydroxyl anthranilic acid hydrochloride 0.16mg
Starch 150mg Magnesium Stearate 0.5%
Method for making:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Embodiment 8: prepare capsule
Formula:
L-Leu 22mg ILE 4.5mg
LYS 20mg L-Phe 6mg
L-threonine 5mg Valine 5.3mg
L-Trp 4mg L-Methionine 22mg
Vitamin A 2400IU Vitamin D2 160IU 11 -->
Sulfuric acid thiamine 4mg Lin Suanna Vitamin B2 Sodium Phosphate 3.6mg
Niacinamide 25mg Vitamin B6 2mg
Folic acid 0.16mg Calcium pantothenate 6mg
Vitamin B12 1.2ug Vitamins C 16mg
Vitamin-E 0.8mg 5-hydroxyl anthranilic acid hydrochloride 0.24mg
Starch 180mg Magnesium Stearate 3%
Method for making: be prepared according to embodiment 1 method for making 2.
Embodiment 9: prepare capsule
Formula:
Method for making:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Embodiment 10: prepare capsule
Formula:
L-Leu 16.5mg ILE 6.5mg
LYS 27.5mg L-Phe 4.5mg
L-threonine 3.7mg Valine 7.5mg
L-Trp 5.5mg L-Methionine 16.5mg
Vitamin A 1800IU Vitamin D2 220IU
Sulfuric acid thiamine 5.5mg Lin Suanna Vitamin B2 Sodium Phosphate 2.7mg
Niacinamide 18mg Vitamin B6 2.75mg
Folic acid 0.22mg Calcium pantothenate 4.5mg
Vitamin B12 0.9ug Vitamins C 22mg
Vitamin-E 1.1mg 5-hydroxyl anthranilic acid hydrochloride 0.18mg
Starch 150mg Magnesium Stearate 1%
Method for making:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
Test example 1: the general character of capsule is investigated
The whole capsules (weighting material in this area be usually also called content) obtained with foregoing embodiments 1-10 are investigated
1, [discriminating]
(1) getting capsule 1, add water 10ml, makes dissolving, filters, and filtrate adds ninhydrin solution 2ml, heating in water bath, and solution shows purple. After testing, whole capsule sample all presents above-mentioned detected result.
(2), in the chromatogram recorded under assay item, the retention time at each seed amino acid peak should be consistent to the retention time of each corresponding reference substance. After testing, whole capsule sample all presents above-mentioned detected result.
(3), in the chromatogram recorded under assay item, the retention time at various VITAMIN peak should be consistent to the retention time of each corresponding reference substance. After testing, whole capsule sample all presents above-mentioned detected result.
(4) fine powder appropriate (being about equivalent to vitamin B15 mg) of this product is got, hydro-oxidation sodium test solution 2.5ml, iron potassuim cyanide test liquid 0.5ml and propyl carbinol 5ml, powerful jolting 2 minutes, placement makes layering, upper strata alcohol liquid shows strong blue-fluorescence, and acid adding makes into acidity, and namely fluorescence disappear, adding alkali again and make alkalize, fluorescence shows again. After testing, whole capsule sample all presents above-mentioned detected result.
(5) getting the fine powder appropriate (being about equivalent to Lin Suanna Vitamin B2 Sodium Phosphate 1mg) of this product, add water 100ml, jolting, and solution is observed aobvious pistac in transmitted light and had yellow-green fluorescence, adds ore deposit acid or alkaline solution, and namely fluorescence disappear. After testing, whole capsule sample all presents above-mentioned detected result.
(6) getting Capsule content and be about 2.0g, add water 15ml, boils, and lets cool, the translucent gelling material of off-white color; Getting this gelling material and be about 1ml, add iodine test solution 1, namely aobvious blue, black-and-blue or atropurpureus, fades after heating gradually. Present method is the classical way checking and whether containing starch in preparation, warp compares with the amino acid-VITAMIN mixed powder not adding starch or compares the method with the mixed powder not adding amino acid-VITAMIN is still reliable, and other each component in prescription does not affect starch coloration and judges.After testing, whole capsule sample all presents above-mentioned detected result.
(7) qualitative/quantitative of Magnesium Stearate: with reference to the precious document (Wei Huizhen etc. of Wei Hui, micro-wave digestion flame) trace lead, nickel, cadmium in aas determination pharmaceutic adjuvant--magnesium stearate, Chinese experimental pharmacology of traditional Chinese medical formulae magazine, 2011,17 (5): 98) method in measures the content of magnesium ion in Capsule content; And, the content of Magnesium Stearate in Capsule content is measured with reference to the method in Yao Chong woods document (Yao Chonglin etc., Magnesium Stearate gas chromatography determination in food, Chinese public health, 2006,22 (2): 244). Measure, with above two kinds of known methods, the capsule sample that all with the addition of Magnesium Stearate all to show containing magnesium and Magnesium Stearate, and after measured, the Magnesium Stearate wherein comprised or the amount of magnesium are identical with the charging capacity of Magnesium Stearate in involved capsule.
(8) Capsules main the qualitative of material gelatin used is determined: the gelatin hollow capsule used for the present invention, can refer to the discrimination method in " the capsule gelatin " that version Chinese Pharmacopoeia four in 2015 records, it is easy to ground determines whether Capsules shell used is make taking gelatin as main material system.
2, [inspection]
(1) weight loss on drying: get this product 10, incline and content, after mixing, gets about 1g, and 105 DEG C of dryings 1 hour, less loss weight must not cross 4%. (Chinese Pharmacopoeia version in 2010 two annex VIIIL).
After testing, whole capsule sample less loss weight is all less than 2.8%.
Under other inspection item of capsule can refer to Chinese Pharmacopoeia version in 2010 two annex I E capsule agent items, relevant every regulation carries out, and all capsule detected result all meets the general regulation of pharmacopeia.
3, [assay]
(1) amino acid
Capsule is carried out content uniformity inspection; Get this product content under content uniformity item, mixed even, grind thin, precision takes in right amount, by water dissolution and dilute finite concentration, filtration, gets continuous filtrate as need testing solution, with suitable amino acidanalyser or high performance liquid chromatograph separation determination; Separately get corresponding amino acid reference substance, make the reference substance solution of respective concentration, be measured in the same method; By external standard method with each amino acid whose content of calculated by peak area.
(2) vitamins C, niacinamide, VITMAIN B1, vitamin B6
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD);
Chromatographic condition and system suitability: be weighting agent with octadecylsilane chemically bonded silica; Taking acetonitrile as mobile phase A, the pentanesulfonic acid sodium solution (Glacial acetic acid containing 0.4%) of 0.04% is Mobile phase B, carries out gradient elution by the regulation in following table; Flow velocity 1.0ml/min, determined wavelength is 275nm, post temperature 25 DEG C; Theoretical stage number calculates by vitamins C peak should be not less than 2000;
Time (minute) Mobile phase A (%) Mobile phase B (%)
-10～0 4 96
0～8 4 96
9～15 10 90
16～27 13 87
Assay method: get this product content under content uniformity item, grind thin, precision takes in right amount (being about equivalent to the amount of 1) and puts in 100ml measuring bottle, add 0.01mol/L hydrochloric acid soln (metaphosphoric acid containing 0.1%) about 80ml, supersound process 30 minutes, lets cool, is diluted to scale, shake even, filter; Precision measures continuous filtrate 10 μ l injection liquid chromatography, record color atlas; Separately get vitamins C, VITMAIN B1, vitamin B6 and niacinamide reference substance appropriate, accurately weighed, dissolve with 0.01mol/L hydrochloric acid soln (metaphosphoric acid containing 0.1%) and quantitatively dilute and make in every 1ml respectively containing the mixing solutions of 0.2mg, 0.05mg, 0.025mg and 0.02mg, product solution (interim brand-new), is measured in the same method in contrast;By external standard method with calculated by peak area, to obtain final product.
(3) Lin Suanna Vitamin B2 Sodium Phosphate
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD);
Chromatographic condition and system suitability: be weighting agent with octadecylsilane chemically bonded silica; Taking the pentanesulfonic acid sodium solution (Glacial acetic acid containing 0.4%) (13: 87) of acetonitrile-0.04% as moving phase, flow velocity 1.0ml/min, determined wavelength is 267nm, post temperature 25 DEG C; Theoretical stage number calculates by Lin Suanna Vitamin B2 Sodium Phosphate peak should be not less than 2000;
Assay method: lucifuge operates; Get this product content under content uniformity item, grind thin, precision takes in right amount (being about equivalent to the amount of 1) and puts in 100ml measuring bottle, add 0.01mol/L hydrochloric acid soln (metaphosphoric acid containing 0.1%) about 80ml, supersound process 10 minutes, put in water-bath and heat 30 minutes, and jolting constantly, let cool, it is diluted to scale, filter; Precision measures continuous filtrate 10 μ l injection liquid chromatography, record color atlas; Separately get Lin Suanna Vitamin B2 Sodium Phosphate reference substance appropriate, accurately weighed, make dissolving with 0.01mol/L hydrochloric acid soln (metaphosphoric acid containing 0.1%) heating in water bath, let cool, and quantitatively the solution about containing 0.03mg in every 1ml is made in dilution, product solution (interim brand-new), is measured in the same method in contrast. By external standard method with calculated by peak area, to obtain final product.
(4) calcium pantothenate
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD);
Chromatographic condition and system suitability: be weighting agent with octadecylsilane chemically bonded silica; Taking acetonitrile as mobile phase A, the phosphoric acid solution (v/v) of 0.1% is Mobile phase B, carries out gradient elution by the regulation in following table; Flow velocity 1.0ml/min, determined wavelength is 210nm, and post temperature is 25 DEG C; Theoretical stage number calculates by calcium pantothenate peak should be not less than 5000;
Time (minute) Mobile phase A (%) Mobile phase B (%)
-10～0 3 97
0～22 3 97
23～36 15 85
Assay method: get this product content under content uniformity item, grind thin, precision takes in right amount (being about equivalent to the amount of calcium pantothenate 12.5mg) and puts in 50ml measuring bottle, add phosphoric acid solution (v/v) the about 40ml of 0.1%, supersound process 20 minutes, lets cool, is diluted to scale, shake even, filter; Precision measures continuous filtrate 10 μ l injection liquid chromatography, record color atlas; Separately getting calcium pantothenate reference substance appropriate, accurately weighed, the phosphoric acid solution (v/v) with 0.1% dissolves, and quantitatively the solution about containing 0.25mg in every 1ml is made in dilution, and product solution in contrast, is measured in the same method; By external standard method with calculated by peak area, to obtain final product.
(5) folic acid
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD);
Chromatographic condition and system suitability: be weighting agent with octadecylsilane chemically bonded silica; Taking acetonitrile as mobile phase A, it is Mobile phase B that 0.05mol/L potassium dihydrogen phosphate (adjusts pH to 3.0 ± 0.2 with phosphoric acid), carries out gradient elution by the regulation in following table; Flow velocity 1.0ml/min, determined wavelength is 280nm, and post temperature is 35 DEG C, and theoretical stage number calculates by folic acid peak should be not less than 5000.
Time (minute) Mobile phase A (%) Mobile phase B (%)
0～17 9 91
18～25 15 85
26～30 9 91
Assay method: lucifuge operates; Get this product content under content uniformity item, grinding thin, precision takes in right amount (being about equivalent to the amount of folic acid 0.5mg) and puts in 25ml measuring bottle, adds 0.2% sodium carbonate solution and is about 20ml, jolting, make to be uniformly dispersed, place 30 minutes, supersound process 30 minutes, let cool, it is diluted to scale, shakes even, filter;Precision measures continuous filtrate 10 μ l injection liquid chromatography, record color atlas; Separately get folic acid reference substance and it is about 10mg, accurately weighed, put in 50ml measuring bottle, add 0.2% sodium carbonate solution 10ml and make dissolving, be diluted with water to scale, in contrast product concentrated wiring liquid; Precision measures reference substance concentrated wiring liquid 1.0ml, puts in 10ml measuring bottle, is diluted with water to scale, makes the solution about containing 0.02mg in every 1ml, and product solution (interim brand-new), is measured in the same method in contrast. By external standard method with calculated by peak area, to obtain final product.
(6) vitamin A, vitamin D2, vitamin-E
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD);
Chromatographic condition and system suitability: be weighting agent with octadecylsilane chemically bonded silica; Taking methanol-water (98: 2) as moving phase; Flow velocity is 0.6ml/min, and determined wavelength is 265nm, and post temperature is 25 DEG C; Theoretical stage number calculates should be not less than 2000 by vitamin A, vitamin D2, vitamin-E peak respectively;
Assay method: lucifuge operates, get this product content under content uniformity item, grind thin, precision takes and (is about equivalent to dehydroretinol 0000IU in right amount, vitamin D2 2000IU, vitamin e1 0.0mg) put in 100ml tool plug Erlenmeyer flask, precision adds 25ml normal hexane, weighed weight, put supersound process 30 minutes in ice bath, take out, weighed weight again, less loss weight is supplied with normal hexane, shake even, filter, precision measures continuous filtrate 10ml, blow dry with nitrogen, residue Virahol dissolves and is settled to 10ml, shake even, filter, precision measures continuous filtrate 10 μ l injection liquid chromatography, record color atlas, separately get, vitamin D2 and vitamin-E reference substance appropriate, accurately weighed, dissolve with Virahol and quantitatively dilute and make respectively containing the mixing solutions of 0.3mg, 2 μ g and 0.5mg in every 1ml, product solution in contrast, is measured in the same method. by external standard method with calculated by peak area, to obtain final product.
(7) 5-hydroxyl anthranilic acid
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD);
Chromatographic condition and system suitability: be weighting agent with octadecylsilane chemically bonded silica; Taking acetonitrile as mobile phase A, 0.05mol/L potassium dihydrogen phosphate (containing 0.04% sodium pentanesulfonate) is Mobile phase B, carries out gradient elution by the regulation in following table; Flow velocity 1.0ml/min, determined wavelength is 240nm, and post temperature is 25 DEG C; Theoretical stage number calculates by 5-hydroxyl anthranilic acid peak should be not less than 5000.
Time (minute) Mobile phase A (%) Mobile phase B (%)
0～10 0 100
10～20 20 80
21～30 0 100
Assay method: get this product content under content uniformity item, grinds thin, and precision takes in right amount (being about equivalent to 5-hydroxyl anthranilic acid 0.5mg) and puts in 25ml measuring bottle, adding 0.01mol/L hydrochloric acid soln and be about 20ml, supersound process 30 minutes, lets cool, it is diluted to scale, shakes even, filter; Precision measures continuous filtrate 10 μ l injection liquid chromatography, record color atlas; Separately get 5-hydroxyl anthranilic acid reference substance appropriate, accurately weighed, make dissolving with 0.01mol/L hydrochloric acid soln, and quantitatively the solution about containing 0.02mg in every 1ml is made in dilution, product solution in contrast, is measured in the same method. By external standard method with calculated by peak area, to obtain final product.
Each capsule of preparing above detects according to above-mentioned [assay] method, and the theoretical charging capacity of the measurement result of 8 seed amino acids and various VITAMIN active ingredient corresponding in capsule is coincide, all in 95～105% scopes of its theory charging capacity separately.
Test example 2: the study on the stability of capsule
The capsule with gelatin hollow capsule packing prepared above is placed in seal-packed aluminum-plastic composite membrane bag respectively, under being placed in 40 ° of C constant temperatures, places June, measure 0 month respectively and the content of each seed amino acid in each capsule during June and VITAMIN. For the same amino acid in same batch of capsule or VITAMIN, below examination calculates the residual content (%) of this activeconstituents:
Residual content (%)=(content ÷ 0 month content in June) × 100%
Ten kinds of capsules of above-described embodiment 1 to embodiment 10, after measured:
Their leucine, Isoleucine, Methionin, methionine(Met), α-amino-isovaleric acid, Threonine, the phenylalanine residual content when June is all greater than 94%, all in 94～98% scopes, meets the regulation that general requirements for pharmaceuticals residual content is greater than 90% completely;
Their vitamin A, vitamin D2, VITMAIN B1, Lin Suanna Vitamin B2 Sodium Phosphate, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin-E, the 5-hydroxyl anthranilic acid residual content when June is all greater than 92%, all in 92～98% scopes, meet the regulation that general requirements for pharmaceuticals residual content is greater than 90% completely;
The vitamins C of ten kinds of capsules, both tryptophanes residual content when June is respectively in 93～96% scopes and in 94～97% scopes.
Test example 21:
The content of the ten of above-described embodiment 1 to embodiment 10 kinds of capsules is taken out from capsule shell and directly uses vial packing, or directly with aluminum plastic compound membrane bag packing, or with hypromellose Capsules (the accurate word F20090002 of traditional Chinese medicines) packing, or with Sargassum polysaccharides Capsules (the accurate word F20050002 of traditional Chinese medicines) packing, or with pectin Capsules (obtaining according to 200910185990.X specification sheets 2 pages of embodiment 1 methods) packing, or with carboxymethyl cellulose Capsules (obtaining according to 200910116242.6 specification sheets, 3 pages of embodiment 1 methods) packing. ten kinds of Capsule content powder stability in these 6 kinds of internal packings directly contacted with medicine is measured according to method described in test example 2.
Result shows, and whole capsule 's content powder is in 6 kinds of packagings
Their leucine, Isoleucine, Methionin, methionine(Met), α-amino-isovaleric acid, Threonine, phenylalanine and the residual content of tryptophane when June are all greater than 94%, all in 94～98% scopes, meet the regulation that general requirements for pharmaceuticals residual content is greater than 90% completely;
This residual content when June of their vitamin A, vitamin D2, VITMAIN B1, Lin Suanna Vitamin B2 Sodium Phosphate, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin-E, 5-hydroxyl anthranilic acid and vitamins C is all greater than 93%, all in 93～98% scopes, meet the regulation that general requirements for pharmaceuticals residual content is greater than 90% completely; Do not appear at the vitamins C of appearance when packing in gelatine capsule agent, the situation of both tryptophanes instability.
Test example 22:
Respectively with reference to formula and the method for making of embodiment 1-10, different is only do not add starch and Magnesium Stearate, obtains 10 kinds of capsules filled by gelatin hollow capsule. Then leucine in 10 kinds of capsules, Isoleucine, Methionin, methionine(Met), α-amino-isovaleric acid, Threonine, phenylalanine and vitamin A, vitamin D2, VITMAIN B1, Lin Suanna Vitamin B2 Sodium Phosphate, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin-E, this residual content when June of 5-hydroxyl anthranilic acid is measured with reference to the method for test example 2, the residual content of whole components that result display comprises tryptophane when June is all greater than 92%, all in 92～97% scopes.Tryptophane and the vitamins C residual content when June is respectively in 77～85% scopes and in 80～84% scopes.
Test example 23:
Respectively with reference to formula and the method for making of embodiment 1-10, different is only do not add starch and Magnesium Stearate, obtain 10 kinds of mixed powders, respectively by these 10 kinds of mixed powders respectively with aluminum plastic compound membrane bag packing, vial packing, hypromellose Capsules or Sargassum polysaccharides Capsules packing. Ten kinds of content powder stability in these 4 kinds of internal packings directly contacted with medicine is measured according to method described in test example 2.
Result shows, and whole capsule 's content powder is in 4 kinds of packagings:
Their leucine, Isoleucine, Methionin, methionine(Met), α-amino-isovaleric acid, Threonine, phenylalanine, the tryptophane residual content when June is all greater than 94%, all in 94～98% scopes, meet the regulation that general requirements for pharmaceuticals residual content is greater than 90% completely;
This residual content when June of their vitamin A, vitamin D2, VITMAIN B1, Lin Suanna Vitamin B2 Sodium Phosphate, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin-E, 5-hydroxyl anthranilic acid, vitamins C is all greater than 93%, all in 93～98% scopes.
Visible, when not adding starch and Magnesium Stearate, composite grain is unstable in gelatin hollow capsule, and is stable in other internal packing material.
Test example 24:
Respectively with reference to formula and the method for making of embodiment 1-10, different is only do not add vitamins C in prescription, obtains 10 kinds of capsules filled by gelatin hollow capsule. Then leucine, Isoleucine, Methionin, methionine(Met), α-amino-isovaleric acid, Threonine, phenylalanine and tryptophane in 10 kinds of capsules and vitamin A, vitamin D2, VITMAIN B1, Lin Suanna Vitamin B2 Sodium Phosphate, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin-E, this residual content when June of 5-hydroxyl anthranilic acid is measured with reference to the method for test example 2, the residual content of whole components that result display comprises tryptophane when June is all greater than 92%, all in 92～97% scopes.
Test example 25:
Respectively with reference to formula and the method for making of embodiment 1-10, different is only do not add tryptophane in prescription, obtains 10 kinds of capsules filled by gelatin hollow capsule. Then leucine in 10 kinds of capsules, Isoleucine, Methionin, methionine(Met), α-amino-isovaleric acid, Threonine, phenylalanine and vitamin A, vitamin D2, VITMAIN B1, Lin Suanna Vitamin B2 Sodium Phosphate, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin-E, vitamins C, this residual content when June of 5-hydroxyl anthranilic acid is measured with reference to the method for test example 2, the residual content of whole components that result display comprises vitamins C when June is all greater than 93%, all in 93～97% scopes.
Test example 26:
Respectively with reference to the formula of embodiment 1-10 and method for making, different is only replaces the starch wherein used as lactose or Microcrystalline Cellulose or deduction do not add starch, obtains 30 kinds of capsules filled by gelatin hollow capsule. Then leucine in these 30 kinds of capsules, Isoleucine, Methionin, methionine(Met), α-amino-isovaleric acid, Threonine, phenylalanine, tryptophane and vitamin A, vitamin D2, VITMAIN B1, Lin Suanna Vitamin B2 Sodium Phosphate, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin-E, vitamins C, this residual content when June of 5-hydroxyl anthranilic acid is measured with reference to the method for test example 2.Result shows, and except tryptophane and vitamins C, the residual content of all other component when June is all greater than 93%, all in 93～98% scopes; But residual content when June of tryptophane and vitamins C is respectively in 79～84% scopes and in 81～86% scopes in these 30 kinds of capsules. This shows when not using starch or used instead the preparation performance that can not realize excellent stability when other auxiliary material is replaced.
Test example 27:
Respectively with reference to the formula of embodiment 1-10 and method for making, different is only replaces the Magnesium Stearate wherein used as stearic acid or Zinic stearas or deduction do not add Magnesium Stearate, obtains 30 kinds of capsules filled by gelatin hollow capsule. Then leucine in these 30 kinds of capsules, Isoleucine, Methionin, methionine(Met), α-amino-isovaleric acid, Threonine, phenylalanine, tryptophane and vitamin A, vitamin D2, VITMAIN B1, Lin Suanna Vitamin B2 Sodium Phosphate, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin-E, vitamins C, this residual content when June of 5-hydroxyl anthranilic acid is measured with reference to the method for test example 2. Result shows, and except tryptophane and vitamins C, the residual content of all other component when June is all greater than 93%, all in 93～98% scopes; But residual content when June of tryptophane and vitamins C is respectively in 82～86% scopes and in 81～84% scopes in these 30 kinds of capsules. This shows when not using Magnesium Stearate or used instead the preparation performance that can not realize excellent stability when other auxiliary material is replaced.
Above test example shows, loads the compound amino acid vitamin mixed powder filled in Capsules, and when taking gelatin as Capsules material, both vitamins C and tryptophane exist taboo, can overcome these taboos by the inventive method.
Test example 28: prepare capsule
Formula and method for making according to CN101773512B (ten thousand Hes) embodiment 1 make the capsule comprising 7 kinds of micro-balls, load by gelatin hollow capsule. Leucine in this kind of capsule, Isoleucine, Methionin, methionine(Met), α-amino-isovaleric acid, Threonine, phenylalanine, tryptophane and vitamin A, vitamin D2, VITMAIN B1, Lin Suanna Vitamin B2 Sodium Phosphate, niacinamide, vitamin B6, folic acid, calcium pantothenate, vitamin-E, vitamins C, this residual content when June of 5-hydroxyl anthranilic acid is measured according to the method above with reference to test example 2. Result display, comprises tryptophane and the residual content of ascorbic whole component when June is all greater than 93%, all in 93～98% scopes. Although capsule prepared by this kind of prior art is stable, but its needs to use extremely complicated production technique.
Test example 3: the water absorbability of capsule 's content powder is investigated
The water absorbability of capsule 's content powder is investigated: capsule 's content powder is placed in vial, January is placed under relative temperature 75%, temperature 25 DEG C of conditions, to powder weighing before and after disposal, the weight increased using 1 the end of month divided by the percentage ratio of initial powder weight as weightening finish percentage ratio (%), and using this weightening finish percentage ratio (%) as evaluation index.
Record,
The weightening finish percentage ratio (%) of whole Capsule content powder of embodiment 1-10 is all in 0.2～1.7% scope;
The weightening finish percentage ratio (%) of test example 22 gained 10 kinds of Capsule content powder is all in 8.6～13.2% scopes;
The weightening finish percentage ratio (%) of the whole Capsule content powder of test example 26 gained is all in 7.4～14.6% scopes;
Test example 27 without the weightening finish percentage ratio (%) of the Capsule content powder (namely only adding starch and do not add Magnesium Stearate) of Magnesium Stearate all in 6.8～9.4% scopes;
Respectively with reference to formula and the method for making of embodiment 1 and embodiment 2, different is only replaces the starch wherein used is dextrin, sucrose, Vltra tears, carboxymethyl starch, sodium starch glycolate, methylcellulose gum or ethyl cellulose, obtaining 14 kinds of capsules, the weightening finish percentage ratio (%) of its content powder is all in 9.2～13.8% scopes.
These results show, when preparation or not piller so that powder directly mixes, it is favourable for adding starch in compound amino acid/vitamine capsule for obtaining the capsule filling with agent of low hygroscopicity, but this kind of effect needs under Magnesium Stearate exists and could obtain.
Embodiments of the present invention are not limited to above-described embodiment, and the various changes made under the prerequisite not departing from objective of the present invention all belong within protection scope of the present invention.

Claims (10)

1. a capsule, it comprises capsule shell and is wrapped in this capsule shell and in powder or the weighting material of particulate state; Described capsule shell take gelatin as the gelatin hollow capsule that main ingredient is made, and described weighting material comprises active substance and pharmaceutical excipient; Described active substance comprises:
L-Leu ILE LYS L-Phe L-threonine Valine L-Trp Such as, methionine(Met) (L-Methionine or DL-methionine) Vitamin A Vitamin D2 VITMAIN B1 (or sulfuric acid thiamine) Lin Suanna Vitamin B2 Sodium Phosphate Niacinamide Vitamin B6 Folic acid Calcium pantothenate Vitamin B12 Vitamins C Vitamin-E 5-hydroxyl anthranilic acid hydrochloride.
2. capsule according to claim 1, its each grain comprises the amount of active substance and is:
L-Leu 14.5～22mg ILE 4.5～7mg LYS 20～30mg L-Phe 4～6mg L-threonine 3.3～5mg Valine 5.3～8mg L-Trp 4～6mg Such as, methionine(Met) (L-Methionine or DL-methionine) 14.5～22mg Vitamin A 1600～2400IU Vitamin D2 160～240IU VITMAIN B1 (or sulfuric acid thiamine) 4～6mg Lin Suanna Vitamin B2 Sodium Phosphate 2.4～3.6mg Niacinamide 1.6～25mg Vitamin B6 2～3mg Folic acid 0.16～0.24mg Calcium pantothenate 4～6mg Vitamin B12 0.8～1.2ug Vitamins C 16～24mg Vitamin-E 0.8～1.2mg 5-hydroxyl anthranilic acid hydrochloride 0.16～0.24mg
Or, its each grain comprises the amount of active substance and is:
L-Leu 16.5～20mg ILE 5.3～6.5mg LYS 22.5～27.5mg L-Phe 4.5～5.5mg L-threonine 3.7～4.6mg Valine 6～7.5mg L-Trp 4.5～5.5mg Such as, methionine(Met) (L-Methionine or DL-methionine) 16.5～20mg Vitamin A 1800～2200IU Vitamin D2 180～220IU VITMAIN B1 (or sulfuric acid thiamine) 4.5～5.5mg Lin Suanna Vitamin B2 Sodium Phosphate 2.7～3.3mg Niacinamide 1.8～22mg Vitamin B6 2.25～2.75mg Folic acid 0.18～0.22mg Calcium pantothenate 4.5～5.5mg Vitamin B12 0.9～1.1ug Vitamins C 18～22mg Vitamin-E 0.9～1.1mg 5-hydroxyl anthranilic acid hydrochloride 0.18～0.22mg
Or, the amount that its each grain comprises active substance is about:
L-Leu 18.3mg ILE 5.9mg LYS 25mg L-Phe 5mg L-threonine 4.2mg Valine 6.7mg L-Trp 5mg Such as, methionine(Met) (L-Methionine or DL-methionine) 18.4mg Vitamin A 2000IU Vitamin D2 200IU 1 --> VITMAIN B1 (or sulfuric acid thiamine) 5mg Lin Suanna Vitamin B2 Sodium Phosphate 3mg
Niacinamide 2mg (or 20mg) Vitamin B6 2.5mg Folic acid 0.2mg Calcium pantothenate 5mg Vitamin B12 1ug Vitamins C 20mg Vitamin-E 1mg 5-hydroxyl anthranilic acid hydrochloride 0.2mg
。
3. capsule according to claim 1, wherein said pharmaceutical excipient is selected from following one or more: lactose, starch, Microcrystalline Cellulose, dextrin, sucrose, Magnesium Stearate, Vltra tears, carboxymethyl starch, sodium starch glycolate, methylcellulose gum, ethyl cellulose etc.
4. capsule according to claim 1, it is characterised in that:
The pharmaceutical excipient total amount comprised in its each grain is 80～400mg, 100～350mg or 100～300mg;
Described in pharmaceutical excipient comprise: starch and Magnesium Stearate;
The amount of starch comprised in its each grain is 80～350mg, 100～300mg or 100～250mg;
The Magnesium Stearate comprised in its each grain accounts for 0.2～10%, 0.5～5% or the 0.5～3% of described weighting material weight;
The weight of the weighting material comprised in its each grain is 200～500mg, 225～450mg or 250～400mg;
The granularity of its weighting material is: the particle of more than 99% sieves by 20 orders, the particle of more than 99% sieves by 24 orders, the particle of more than 95% sieves by 65 orders by the particle of 50 orders sieves or more than 90%; And/or
It is that the directly encapsulated mode of powder prepares.
5. capsule according to claim 1, it is that the method by comprising the following steps prepares:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
6. preparing the method for capsule, described capsule comprises capsule shell and is wrapped in this capsule shell and in powder or the weighting material of particulate state; Described capsule shell take gelatin as the gelatin hollow capsule that main ingredient is made, and described weighting material comprises active substance and pharmaceutical excipient; Described active substance comprises:
L-Leu ILE LYS L-Phe L-threonine Valine L-Trp Such as, methionine(Met) (L-Methionine or DL-methionine) Vitamin A Vitamin D2 VITMAIN B1 (or sulfuric acid thiamine) Lin Suanna Vitamin B2 Sodium Phosphate Niacinamide Vitamin B6 Folic acid Calcium pantothenate Vitamin B12 Vitamins C Vitamin-E 5-hydroxyl anthranilic acid hydrochloride;
The method comprises the following steps:
I each solid materials is pulverized into the powder by 65 order sieves by () respectively;
(ii) each mixing of materials is even, become mixed powder eventually;
(iii) being filled in hard capsule case by mixed powder eventually, capsule body and capsule cap are set with, sealing, to obtain final product.
7. method according to claim 6, each grain of described capsule comprises the amount of active substance and is:
L-Leu 14.5～22mg ILE 4.5～7mg LYS 20～30mg L-Phe 4～6mg L-threonine 3.3～5mg Valine 5.3～8mg L-Trp 4～6mg Such as, methionine(Met) (L-Methionine or DL-methionine) 14.5～22mg Vitamin A 1600～2400IU Vitamin D2 160～240IU VITMAIN B1 (or sulfuric acid thiamine) 4～6mg Lin Suanna Vitamin B2 Sodium Phosphate 2.4～3.6mg Niacinamide 1.6～25mg Vitamin B6 2～3mg Folic acid 0.16～0.24mg Calcium pantothenate 4～6mg Vitamin B12 0.8～1.2ug Vitamins C 16～24mg Vitamin-E 0.8～1.2mg 5-hydroxyl anthranilic acid hydrochloride 0.16～0.24mg
Or, each grain of described capsule comprises the amount of active substance and is:
L-Leu 16.5～20mg ILE 5.3～6.5mg LYS 22.5～27.5mg L-Phe 4.5～5.5mg L-threonine 3.7～4.6mg Valine 6～7.5mg L-Trp 4.5～5.5mg Such as, methionine(Met) (L-Methionine or DL-methionine) 16.5～20mg Vitamin A 1800～2200IU Vitamin D2 180～220IU VITMAIN B1 (or sulfuric acid thiamine) 4.5～5.5mg Lin Suanna Vitamin B2 Sodium Phosphate 2.7～3.3mg Niacinamide 1.8～22mg Vitamin B6 2.25～2.75mg Folic acid 0.18～0.22mg Calcium pantothenate 4.5～5.5mg Vitamin B12 0.9～1.1ug Vitamins C 18～22mg Vitamin-E 0.9～1.1mg 5-hydroxyl anthranilic acid hydrochloride 0.18～0.22mg
Or, the amount that each grain of described capsule comprises active substance is about:
L-Leu 18.3mg ILE 5.9mg LYS 25mg L-Phe 5mg L-threonine 4.2mg Valine 6.7mg L-Trp 5mg Such as, methionine(Met) (L-Methionine or DL-methionine) 18.4mg Vitamin A 2000IU Vitamin D2 200IU VITMAIN B1 (or sulfuric acid thiamine) 5mg Lin Suanna Vitamin B2 Sodium Phosphate 3mg Niacinamide 2mg (or 20mg) Vitamin B6 2.5mg Folic acid 0.2mg Calcium pantothenate 5mg Vitamin B12 1ug Vitamins C 20mg Vitamin-E 1mg 5-hydroxyl anthranilic acid hydrochloride 0.2mg
。
8. method according to claim 6, wherein said pharmaceutical excipient is selected from following one or more: lactose, starch, Microcrystalline Cellulose, dextrin, sucrose, Magnesium Stearate, Vltra tears, carboxymethyl starch, sodium starch glycolate, methylcellulose gum, ethyl cellulose etc.
9. method according to claim 6, it is characterised in that:
The pharmaceutical excipient total amount comprised in each grain of described capsule is 80～400mg, 100～350mg, 100～300mg;
Pharmaceutical excipient described in described capsule comprises: starch and Magnesium Stearate;
The amount of starch comprised in each grain of described capsule is 80～350mg, 100～300mg, 100～250mg;
The Magnesium Stearate comprised in each grain of described capsule accounts for 0.2～10%, 0.5～5%, the 0.5～3% of described weighting material weight;
The weight of the weighting material comprised in each grain of described capsule is 200～500mg, 225～450mg or 250～400mg.
10. method according to claim 6, it is characterised in that:
The granularity of described capsule weighting material is: the particle of more than 99% sieves by 20 orders;
The granularity of described capsule weighting material is: the particle of more than 99% sieves by 24 orders;
The granularity of described capsule weighting material is: the particle of more than 95% sieves by 50 orders; And/or
The granularity of described capsule weighting material is: the particle of more than 90% sieves by 65 orders.
CN201610060208.1A 2016-01-28 2016-01-28 Compound amino acid capsule agent Active CN105663107B (en)

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