CN106821998A - Prepare the method and its compound amino acid capsule composition of vitaminAD micropill - Google Patents

Prepare the method and its compound amino acid capsule composition of vitaminAD micropill Download PDF

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Publication number
CN106821998A
CN106821998A CN201710194040.8A CN201710194040A CN106821998A CN 106821998 A CN106821998 A CN 106821998A CN 201710194040 A CN201710194040 A CN 201710194040A CN 106821998 A CN106821998 A CN 106821998A
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Prior art keywords
micropill
vitamin
vitaminad
gram
amino acid
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Granted
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CN201710194040.8A
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CN106821998B (en
Inventor
彭潇波
马俊
陈广进
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Shenzhen Wanhe Pharmaceutical Co Ltd
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Shenzhen Wanhe Pharmaceutical Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1658—Proteins, e.g. albumin, gelatin
    • 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, 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
    • A61K31/185—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, pantothenic acid
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
    • 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
    • A61K31/519—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
    • A61K31/70—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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs

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  • Animal Behavior & Ethology (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Emergency Medicine (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Method and its compound amino acid capsule composition the present invention relates to prepare vitaminAD micropill.Specifically, on the one hand, the present invention relates to a kind of vitaminAD micropill, wherein comprising vitamin A and calciferol；2~200,000 I.U. vitamin As, 0.2~20,000 I.U. vitamin Ds are included in its every 1 gram of micropill2.Originally the preparation method for being related to the vitaminAD micropill is returned, the capsule of the compound recipe amino acid vitamin micro pill comprising the vitaminAD micropill.The characteristics of vitaminAD micropill of the present invention and the compound amino acid vitamin capsule prepared using it are had better than existing product.

Description

Prepare the method and its compound amino acid capsule composition of vitaminAD micropill
Technical field
The present invention relates to a kind of vitaminAD micropill, it is this with it is small and concentrate particle diameter and be particularly suitable for application as The filler or filler component of hard capsule.The invention further relates to the preparation method of this vitaminAD micropill.Other sheet Invention further relates to a kind of micro pill capsule and preparation method thereof, is to be related to one kind comprising 8 kinds of amino acid and 11 kinds of vitamins specifically The capsule of micropill, also referred to as compound amino acid capsule (8-11), further relate to the preparation method of the capsule.
Background technology
Protein is the material base of human life activity, and human body items physiological function, particularly immunologic function, cell are damaged The repair function of wound and function of growing, whether normal have extremely close relationship with it is metabolized.Under normal circumstances, people Body is to obtain various amino acid by the protein in food to ensure the normal of body protein metabolism.Closed in human body protein Into in 20 kinds of required amino acid, wherein having 8 kinds of amino acid for essential amino acid, this 8 kinds of amino acid are bodies interior originally Body can not synthesize and be necessarily dependent upon external supply.They are isoleucine, leucine, lysine, phenylalanine, Soviet Union's ammonia Acid, valine, methionine and tryptophan.For protein synthesis, this 8 kinds of amino acid are indispensable, and not enough in content Or the synthesis of protein can be all influenceed when matching unbalanced.
During generation in disease, development and recovery from illness, due to various pathology and stress reaction, it is in addition improper diet or Digestive tract function is affected, and the disorder of protein metabolism usually occurs, and the disorder of protein metabolism is often led with disease The duration of the death of cause, the generation of complication and disease is closely related.Therefore, in clinical practice, the supply of nitrogen matter is Indispensable, effective treatment means.
Since World War II, the U.S. takes the lead in releasing protein hydrolysate, for the supply of nitrogen matter in lysis.50 In the age, Japan realizes the large scale fermentation of amino acid and prepared by purifying, for crystal type amino acid transfusion provides favourable skill Art ensures.Into the 1970s and 1980s, amino acid transfusion is constantly the treatment of clinically all kinds of acute diseases, seriously disease, particularly right Urgent patient and be unable to oral consumption patient treatment provide strong support.
But for the treatment of chronic disease, particularly can oral consumption patient treatment, the limitation right and wrong of amino acid transfusion It is often obvious.In terms of the characteristics of being metabolized from vivo acid, amino acid transfusion may cause vivo acid match it is not normal, infused Serum amino acid excessive concentration in journey, transfusion stop after serum amino acid concentration decline rapidly, aggravates liver denitrogen bear, while It is possible to cause the adverse reactions such as infusion reaction, vein blood vessel inflammation.What is more important amino acid transfusion is only in short In play the role of to promote positive nitrogen equilibrium, long-term use therapeutic effect is obvious.
Just because of this, while parenteral nutrition develops, development abroad is simultaneously perfect by crystalline amino acid, hydrolysis egg In vain, various enteral nutrition preparations of the nitrogen source such as complete protein composition.Enteral nutrition preparation is mainly and is orally ingested, there is provided required Nutrient meet body metabolism the need for, EA be conducive to compared with parenteral nutrition keep enteron aisle 26S Proteasome Structure and Function it is complete Whole property, prevents intestinal mucosa atrophy and the bacterial translocation caused by long-term parenteral, is conducive to improving the immunity of body.
At present, the treatment of EA is paid much attention in domestic and international clinical practice, particularly in the long-term treatment of chronic disease In, the ratio of enteral nutrition treatment greatly exceed the treatment of parenteral nutrition.As long as " gastrointestinal function is allowed, as far as possible using enteral Nutrition " is the principle of clinic nutrition treatment.Therefore, people are badly in need of solving the medicine for enteral nutrition treatment.Due to amino acid It is unstable, cause Amino Acid Oral Preparation product stability poor, govern the application of Amino Acid Oral Preparation product.Chinese patent CN1781486, it is entitled：A kind of amino acid and vitamine capsule preparation and preparation method thereof, it is believed that the invention system Standby product stability is bad, and at 12 months, product appearance substantially changed colour and product content is decreased obviously.In addition, CN101773512A discloses a kind of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules and preparation method thereof, wherein in capsule shells Including 7 kinds of micropills, it is believed that 7 kinds of micropills in the micro pill capsule because performance is different and can caused by micropill mixing, encapsulating capsule when go out The existing substantially uneven phenomenon of indivedual micropill contents.Additionally, the vitaminAD microballon used in CN101773512A can directly from RIKEN CORPORATION buys, or can buy Riken Vitamin Co., Ltd.'s imports to the Riken of China from China Dry AD-B100/10P.However, the present inventor has found under study for action, using it is such manage the vitaminAD microballon that grinds with comprising After the vitamin micro pill a mixing of niacinamide, calcium pantothenate etc., vitamin A, D in these vitaminAD microballons have significantly The tendency of content reduction, overcomes this defect so as to clinically to provide a kind of amino acid and Wei Sheng with superior quality Cellulose product is that those skilled in the art urgently expect.
The content of the invention
Goal of the invention of the invention is to provide a kind of vitaminAD micropill.Another goal of the invention of the invention is to provide The preparation method of this vitaminAD micropill.Goal of the invention of the invention is to provide one kind to contain 8 kinds of amino acid and 11 kinds of dimensions The capsule of the micropill of raw element.Another goal of the invention of the invention is the preparation method for providing this capsule.It is unexpected Discovery, using vitaminAD micropill obtained in the inventive method, by its with of the present invention containing 8 kinds of amino acid and 11 kinds After the micropill mixing of vitamin, this mix preparation there is excellent chemical stability to be particularly show as vitamin A and Wei Sheng The chemical stability of plain D2.The present invention is accomplished based on upper discovery.
Specifically, first aspect present invention provides a kind of vitaminAD micropill, wherein comprising vitamin A and vitamin D2。
The vitaminAD micropill of any embodiment, includes 2~200,000 according to a first aspect of the present invention in its every 1 gram of micropill I.U. vitamin A, such as include 5~150,000 I.U. vitamin As in its every 1 gram of micropill, such as in its every 1 gram of micropill comprising 8~ 100,000 I.U. vitamin As are included in 120000 I.U. vitamin As, such as its every 1 gram of micropill.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein the vitamin A is to tie up life The form of other esters of plain A or Retinol Palmitate or vitamine A acetate or vitamin A is added to the dimension In raw element AD micropills.
The vitaminAD micropill of any embodiment, includes 0.2~2 according to a first aspect of the present invention in its every 1 gram of micropill Ten thousand I.U. vitamin Ds20.5~1.5 ten thousand I.U. are included in (it is also referred to as calciferol, ostelin etc.), such as its every 1 gram of micropill Vitamin D2, such as 0.8~1.2 ten thousand I.U. vitamin Ds are included in its every 1 gram of micropill2, such as 10,000 are included in its every 1 gram of micropill I.U. vitamin D2。
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also containing edible vegetable oil for example Corn oil, soybean oil, peanut oil, sunflower oil etc..
The vitaminAD micropill of any embodiment, plants in its every 1 gram of micropill comprising edible according to a first aspect of the present invention Thing 100~200mg of oil, such as such as 120~160mg, 130~150mg.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also containing sorbitan fatty Acid esters, such as span20 (i.e. Arlacel-20), span40 (i.e. Arlacel-40), span60 (i.e. Arlacel-60), span65 (i.e. sapn- 65), span80 (i.e. Arlacel-80), span85 (i.e. Arlacel-85).
The vitaminAD micropill of any embodiment, includes dehydration mountain according to a first aspect of the present invention in its every 1 gram of micropill Pears 2~20mg of alcohol fatty acid ester, such as such as 2~15mg, 2~12mg.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also containing gelatin.
The vitaminAD micropill of any embodiment, includes gelatin 400 according to a first aspect of the present invention in its every 1 gram of micropill ~700mg, such as 500~650mg, such as 550~600mg.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also containing sucrose.
The vitaminAD micropill of any embodiment, includes sucrose 100 according to a first aspect of the present invention in its every 1 gram of micropill ~300mg, such as 150~250mg, such as 180~240mg.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also containing preservative.At one In embodiment, the preservative is selected from Sodium Benzoate, dehydroactic acid sodium, sorbic acid, potassium sorbate, mud parker methyl ester, Ni Bo Golden ethyl ester, the golden propyl ester of mud pool and combinations thereof.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, in its every 1 gram of micropill comprising anti-corrosion 1~ 5mg, such as 1.5~3mg, such as 2~3mg.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein containing Sodium Benzoate, every 1 gram micro- 0.2~2mg of Sodium Benzoate, such as such as 0.5~1.5mg, 0.75~1mg are included in ball.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein contain dehydroactic acid sodium, every 1 gram 0.5~5mg of dehydroactic acid sodium, such as such as 1~3mg, 1.2~2mg are included in micropill.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, it is the method according to comprising the following steps Prepare：
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing are made into dissolving, obtains oil Property liquid；Separately gelatin and sucrose are dissolved in the water, preservative is added, is stirred to dissolve, obtain aqueous solution；
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing obtains emulsion；
(3) by step (2) gained LS, dry, obtain vitaminAD micropill.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein in step (1), described oiliness Liquid be it is obtained at a temperature of 35~100 DEG C, it is e.g. obtained at a temperature of 35~80 DEG C.It has been found that for example below In embodiment 1-5, effective dissolving of whole materials cannot be realized when this temperature is less than 30 DEG C.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein in step (1), described is aqueous Liquid be it is obtained at a temperature of 40~100 DEG C, it is e.g. obtained at a temperature of 50~85 DEG C.It has been found that for example below In embodiment 1-5, under above-mentioned treatment temperature, it is possible to use relatively more a small amount of water is to be capable of achieving overall preparation technology, such as The amount of water is 2~6 times of gelatin amount, e.g. the 3~6 of gelatin amount times.It has been found that for example below in embodiment 1-5, when This temperature cannot realize effective dissolving of whole materials when being less than 40 DEG C, or the water for needing particularly marked degree increases for example aobvious Work increases to more than 9 times of gelatin amount.
The vitaminAD micropill of any embodiment, wherein step (2) medium oil liquid and water according to a first aspect of the present invention Property liquid mixing temperature be 50~100 DEG C, such as 60~80 DEG C.It has been found that for example below in embodiment 1-5, temperature herein The emulsion of uniform particle sizes can be effectively formed in the range of degree.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, the wherein spraying described in step (3) are done Dry is to make LS to temperature be less than in 70 DEG C of environment and dry to make to form particulate.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, the wherein spraying described in step (3) are done Dry is to make in LS to the environment of 20~70 DEG C of temperature and drying makes to form particulate.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, the wherein spraying described in step (3) are done Dry is to make to make to form particulate in LS to the environment of 20~70 DEG C of temperature and through fluidized bed drying.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, the wherein spraying described in step (3) are done It is dry be make LS to temperature less than in -20 DEG C of environment then (optional in the case where state is fluidized) make into through lyophilization it is micro- Grain；
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, the wherein spraying described in step (3) are done It is dry be make LS to temperature less than in -30 DEG C of environment then (optional in the case where state is fluidized) make into through lyophilization it is micro- Grain；
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, the wherein spraying described in step (3) are done It is dry be make LS to temperature less than in -40 DEG C of environment then (optional in the case where state is fluidized) make into through lyophilization it is micro- Grain；
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein temperature is low described in step (3) It is space environment to be carried out by using liquid nitrogen cool down acquisition in -20 DEG C of environment.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also including lubricant.At one In embodiment, described lubricant is added before micropill drying, during drying or after drying.In an embodiment In, the lubricant be selected from magnesium stearate, stearic acid, calcium stearate, talcum powder, silica, molecular weight 4000-6000 it is poly- Ethylene glycol etc. and combinations thereof.In one embodiment, the lubricant accounts for the vitaminAD micropill weight after drying 0.005~1%, such as 0.1~0.5%.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein drying is described in step (3) So that the moisture in the micropill in terms of loss on drying less than 10%, be, for example, less than 7%.The loss on drying is 105 DEG C drying determines what is obtained in 2 hours.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, its average grain diameter is at 200~1200 μm In the range of, particularly its average grain diameter is in 300~900 μ ms.It has been found that for example passing through in embodiment 1-5 below The intensity adjustment of emulsification procedure can obtain desired average grain diameter in step (2), such as can be obtained when emulsion strength is high The smaller micropill of average grain diameter, and the average grain diameter of gained micropill is than larger when emulsion strength is relatively low.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein in the model of average grain diameter ± 50 μm Micropill number in enclosing accounts for more than the 60% of total micropill number, for example, account for more than the 70% of total micropill number, for example, account for total micropill number More than 80%.This performance shows that micropill of the present invention has very narrow particle size distribution.It has been had now surprisingly been found that, example Such as, when appropriate sucrose is added in micropill, the narrow particle size distribution of above-mentioned presentation can be obtained in embodiment 1-5 below Micropill；But when without sucrose (such as without sucrose in Examples below 1-5) or change plus other water solubilitys it is good Micropill number during good carbohydrate in the range of average grain diameter ± 50 μm accounts for total micropill number and is below 35%, show to be not added with sucrose or Using other carbohydrates instead can not obtain the micropill of narrow particle size distribution.
Further, second aspect present invention is provided and prepares the vitaminAD micropill any reality of such as first aspect present invention The method for applying vitaminAD micropill described in scheme, it comprises the following steps：
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing are made into dissolving, obtains oil Property liquid；Separately gelatin and sucrose are dissolved in the water, preservative is added, is stirred to dissolve, obtain aqueous solution；
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing obtains emulsion；
(3) by step (2) gained LS, dry, obtain vitaminAD micropill.
The method of any embodiment, includes 2~20 according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill 5~150,000 I.U. vitamin As are included in ten thousand I.U. vitamin As, such as its every 1 gram of micropill, such as 8 are included in its every 1 gram of micropill 100,000 I.U. vitamin As are included in~12 ten thousand I.U. vitamin As, such as its every 1 gram of micropill.
The method of any embodiment according to a second aspect of the present invention, wherein the vitamin A is with vitamin A or dimension The form of other esters of raw element A palmitates or vitamine A acetate or vitamin A is added to the vitaminAD micropill In.
The method of any embodiment according to a second aspect of the present invention, in every 1 gram of the vitaminAD micropill comprising 0.2~ 20000 I.U. vitamin Ds20.5~1.5 ten thousand are included in (it is also referred to as calciferol, ostelin etc.), such as its every 1 gram of micropill I.U. vitamin D2, such as 0.8~1.2 ten thousand I.U. vitamin Ds are included in its every 1 gram of micropill2, such as included in its every 1 gram of micropill 10000 I.U. vitamin Ds2。
The method of any embodiment according to a second aspect of the present invention, the edible vegetable oil for example corn oil, soybean oil, Peanut oil, sunflower oil etc..
The method of any embodiment, includes edible in every 1 gram of the vitaminAD micropill according to a second aspect of the present invention 100~200mg of vegetable oil, such as 120~160mg, such as 130~150mg.
The method of any embodiment according to a second aspect of the present invention, the sorbitan fatty acid ester, for example span20、span40、span60、span65、span80、span85。
The method of any embodiment, includes dehydration according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill 2~20mg of Span, such as 2~15mg, such as 2~12mg.
The method of any embodiment, includes gelatin according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill 400~700mg, such as 500~650mg, such as 550~600mg.
The method of any embodiment, includes sucrose according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill 100~300mg, such as 150~250mg, such as 180~240mg.
The method of any embodiment according to a second aspect of the present invention, the preservative is selected from Sodium Benzoate, dehydroactic acid Sodium, sorbic acid, potassium sorbate, mud parker methyl ester, mud moor gold ethyl ester, the golden propyl ester of mud pool and combinations thereof.
The method of any embodiment, includes anti-corrosion according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill 1~5mg of agent, such as 1.5~3mg, such as 2~3mg.
The method of any embodiment, includes benzene first according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill Sour 0.2~2mg of sodium, such as such as 0.5~1.5mg, 0.75~1mg.
The method of any embodiment, includes dehydrogenation according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill 0.5~5mg of sodium acetate, such as 1~3mg, such as 1.2~2mg.
The method of any embodiment according to a second aspect of the present invention, wherein in step (1), described oiliness liquid is 35 It is obtained at a temperature of~100 DEG C, it is e.g. obtained at a temperature of 35~80 DEG C.It has been found that when this temperature is less than 30 DEG C Effective dissolving of whole materials cannot be realized.
The method of any embodiment according to a second aspect of the present invention, wherein in step (1), described aqueous solution is 40 It is obtained at a temperature of~100 DEG C, it is e.g. obtained at a temperature of 50~85 DEG C.It has been found that under above-mentioned treatment temperature, can It is to be capable of achieving overall preparation technology with the water using fewer amount, the amount of such as water is 2~6 times of gelatin amount, e.g. bright 3~6 times of glue amount.It has been found that effective dissolving of whole materials cannot be realized when this temperature is less than 40 DEG C, or need Water particularly marked degree increases and is for example increased significantly to more than 9 times of gelatin amount.
The method of any embodiment according to a second aspect of the present invention, wherein step (2) medium oil liquid mixes with aqueous solution Temperature be 50~100 DEG C, such as 60~80 DEG C.It has been found that uniform particle sizes can be effectively formed in this temperature range Emulsion.
The method of any embodiment according to a second aspect of the present invention, wherein the spray drying described in step (3) is to make breast Liquid is sprayed in environment of the temperature less than 70 DEG C and drying makes to form particulate.
The method of any embodiment according to a second aspect of the present invention, wherein the spray drying described in step (3) is to make breast Liquid is sprayed in the environment of 20~70 DEG C of temperature and drying makes to form particulate.
The method of any embodiment according to a second aspect of the present invention, wherein the spray drying described in step (3) is to make breast Liquid is sprayed in the environment of 20~70 DEG C of temperature and makes to form particulate through fluidized bed drying.
The method of any embodiment according to a second aspect of the present invention, wherein the spray drying described in step (3) is to make breast Liquid is sprayed to temperature, and less than in -20 DEG C of environment, then (optional in the case where state is fluidized) makes into particulate through lyophilization；
The method of any embodiment according to a second aspect of the present invention, wherein the spray drying described in step (3) is to make breast Liquid is sprayed to temperature, and less than in -30 DEG C of environment, then (optional in the case where state is fluidized) makes into particulate through lyophilization；
The method of any embodiment according to a second aspect of the present invention, wherein the spray drying described in step (3) is to make breast Liquid is sprayed to temperature, and less than in -40 DEG C of environment, then (optional in the case where state is fluidized) makes into particulate through lyophilization；
The method of any embodiment according to a second aspect of the present invention, temperature is less than -20 DEG C wherein described in step (3) Environment is space environment to be carried out by using liquid nitrogen cool down acquisition.
The method of any embodiment, dries described in being so that wherein described in step (3) according to a second aspect of the present invention Moisture in micropill, less than 10%, is, for example, less than 7% in terms of loss on drying.The loss on drying is small in 105 DEG C of dryings 2 When determine and obtain.
The method of any embodiment according to a second aspect of the present invention, vitaminAD micropill its average grain diameter obtained by it In 200~1200 μ ms, particularly its average grain diameter is in 300~900 μ ms.It has been found that by step (2) The intensity adjustment of emulsification procedure can obtain desired average grain diameter, such as average grain diameter ratio can be obtained when emulsion strength is high Less micropill, and the average grain diameter of gained micropill is than larger when emulsion strength is relatively low.
The method of any embodiment according to a second aspect of the present invention, the vitaminAD micropill obtained by it, wherein flat Micropill number in the range of equal particle diameter ± 50 μm accounts for more than the 60% of total micropill number, for example, account for more than the 70% of total micropill number, example Such as account for more than the 80% of total micropill number.This performance shows that micropill of the present invention has very narrow particle size distribution.Go out The discovery that people expects, when appropriate sucrose is added in micropill, can obtain the micropill of narrow particle size distribution；But ought not Micropill number during addition sucrose or when changing the carbohydrate for adding other water solubilitys good in the range of average grain diameter ± 50 μm is accounted for always Micropill number is below 35%, shows to be not added with sucrose or use other carbohydrates instead that the micropill of narrow particle size distribution can not be obtained.
It has been found that vitaminAD micropill of the invention can substitute compound amino acid capsule composition completely for example including The vitaminAD microballon from RIKEN CORPORATION's import used in 8 kinds of amino acid and 11 kinds of capsules of vitamin micro pill.
Therefore, third aspect present invention provides a kind of capsule, it includes 7 kinds of spherical or almost spherical micropills, with And the capsule shells of these micropills are wrapped up, 8 kinds of amino acid and 11 kinds of vitamins, and 7 kinds of micropills are included in 7 kinds of micropills And its weight proportion (in parts by weight) is：
The capsule of any embodiment according to a third aspect of the present invention, wherein the thiamine mononitrate micropill, vitamin are micro- Ball a, vitamin micro pill b, amino acid micropill b, can be independently of one another known, for example, can be that CN101773512A is remembered Carry.
The capsule of any embodiment according to a third aspect of the present invention, wherein the vitaminAD micropill is such as the present invention Described in first aspect any embodiment, or as obtained by second aspect present invention any embodiment.
The capsule of any embodiment according to a third aspect of the present invention, wherein, described amino acid micropill a is included with weight Amount part meter：
The capsule of any embodiment according to a third aspect of the present invention, wherein, described amino acid micropill a is included with weight Amount part meter：
The capsule of any embodiment according to a third aspect of the present invention, wherein described vitamin C micro-pill is included with weight Amount part meter：
The capsule of any embodiment according to a third aspect of the present invention, wherein described vitamin C micro-pill is comprising following Weight portion meter：
The capsule of any embodiment according to a third aspect of the present invention, it includes 7 kinds of spherical or almost spherical micropills, And wrap up the capsule shells of these micropills, include 8 kinds of amino acid and 11 kinds of vitamins in 7 kinds of micropills, and it is described 7 kinds it is micro- Ball and its weight proportion (in parts by weight) are：
Wherein, described thiamine mononitrate micropill is included in parts by weight：
Described vitamin micro pill a is included in parts by weight：
Described amino acid micropill a is included in parts by weight：
Described vitamin micro pill b is included in parts by weight：
Described amino acid micropill b is included in parts by weight：
Described vitamin C micro-pill is included in parts by weight：
The capsule of any embodiment according to a third aspect of the present invention, wherein, 7 kinds of micropills and its weight proportion (in parts by weight) it is：
Wherein, described thiamine mononitrate micropill is included in parts by weight：
Described vitamin micro pill a is included in parts by weight：
Described amino acid micropill a is included in parts by weight：
Described vitamin micro pill b is included in parts by weight：
Amino acid micropill b is included in parts by weight：
Described vitamin C micro-pill includes following weight portion meter：
The capsule of any embodiment according to a third aspect of the present invention, wherein, 7 kinds of micropills and its weight proportion (in parts by weight) it is：
Thiamine mononitrate micropill 6.88
Vitamin micro pill a 17.1
Amino acid micropill a 36.8
Vitamin micro pill b 12
Amino acid micropill b 7.56
Vitamin C micro-pill 13.4
VitaminAD micropill 6.2
Wherein, described thiamine mononitrate micropill includes following weight portion meter：
Thiamine mononitrate 25
Lactose 45
Starch 4.5
Calcium carboxymethylcellulose 7.5
Methylcellulose 2.2
Hydroxypropyl cellulose 1.9
Titanium dioxide 2.3
Microcrystalline cellulose 11.6
Described vitamin micro pill a is included in parts by weight：
Niacinamide 36
Calcium pantothenate 10
Vitamin B6 4.3
Lactose 7.7
Calcium carboxymethylcellulose 14
Hydroxypropyl cellulose 1.8
Microcrystalline cellulose 20
Starch 8.3
Described amino acid micropill a is included in parts by weight：
ILE 4.6
L-Leu 14.2
LYS 19.3
L-phenylalanine 3.9
L-threonine 3.3
Valine 5.2
METHIONINE 14.3
Lactose 17.6
Starch 2.1
Methylcellulose 2.0
Hydroxypropyl cellulose 1.2
Microcrystalline cellulose 9.7
Uranidin 0.16
Calcium carboxymethylcellulose 2.44
Lauryl sodium sulfate 1.5
Described vitamin micro pill b is included in parts by weight：
5- hydroxyl anthranilic acid hydrochlorides 0.684
Vitamin B2 9.24
Folic acid 0.56
Vitamin B12 0.0028
Lactose 44.17
Microcrystalline cellulose 31.1
Macrogol 6000 0.57
Calcium carboxymethylcellulose 0.62
Starch 4.68
Described amino acid micropill b is included in parts by weight：
L-Trp 21.18
Vitamin E 4.56
Lactose 25.25
Starch 19.55
Calcium carboxymethylcellulose 1.66
Methylcellulose 1.785
Hydroxypropyl cellulose 1.15
Haematochrome 0.425
Uranidin 0.0425
Alumina silicate 15.39
Described vitamin C micro-pill is included in parts by weight：
Vitamin C 46.3
Lactose 27.1
Starch 6.03
Microcrystalline cellulose 7.56
Calcium carboxymethylcellulose 4.5
Macrogol 6000 3.8
Methylcellulose 1.8
Chocolate pigment 0.29
Hydroxypropyl cellulose 2.62
Citric acid 3。
The capsule of any embodiment according to a third aspect of the present invention, it has matching somebody with somebody described in specification any embodiment Square ratio.
Fourth aspect present invention provides the preparation method of capsule described in third aspect present invention any embodiment：First Thiamine mononitrate micropill, vitamin micro pill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, vitamin C are prepared respectively Micropill, vitaminAD micropill, then this seven kinds of micropills are mixed in proportion, load capsule；
Wherein,
Described vitaminAD micropill is as described in first aspect present invention any embodiment, or such as present invention second Aspect any embodiment methods described is prepared；
The preparation method of the circular micropill of described 6 kinds is comprised the following steps independently of one another：
(1) raw material is weighed in proportion, mixed material；
(2) it is that wetting agent prepares softwood with water, the kneading time is 4~10 minutes；
(3) circle ball is granulated, mesh size is 0.9 millimeter, and circle ball speed is 40~60 hertz；
(4) EAT be 45~65 DEG C fluidized drying or 50~60 DEG C under the conditions of be vacuum dried.
Method described in any embodiment according to a fourth aspect of the present invention, wherein the thiamine mononitrate micropill, vitamin The preparation method of micropill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b and vitamin C micro-pill is respectively：
(1) preparation method of thiamine mononitrate micropill is：Thiamine mononitrate and pharmaceutic adjuvant are mixed in proportion, is wetting with water Agent prepares softwood, integrates 4~6 minutes time；Granulation circle ball, granulates speed 0.3pm, 0.9 millimeter of mesh size, and circle ball speed is 50~60 hertz；Fluidized drying, 45~65 DEG C of EAT；Sieve to obtain thiamine mononitrate white micropill；
(2) preparation method of vitamin micro pill a is：Niacinamide, calcium pantothenate, vitamin B6 and auxiliary material are mixed, is with water Wetting agent prepares softwood, and the kneading time is 4~8 minutes；Granulation circle ball, granulates speed 0.3pm, 0.9 millimeter of mesh size, circle ball 50~60 hertz of speed；Fluidized drying, EAT is 45~65 DEG C；Sieve to obtain vitamins white micropill；
(3) preparation method of amino acid micropill a is：By ILE, L-Leu, LYS, L- phenylpropyl alcohols Propylhomoserin, L-threonine, Valine, METHIONINE and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, during kneading Between be 15~20 minutes, granulation circle ball granulates speed 0.3pm, and 0.9 millimeter of mesh size, circle ball speed is 40~50 hertz, It is vacuum dried under the conditions of 50 DEG C~60 DEG C；Sieve to obtain amino acid yellow micropill；
(4) preparation method of vitamin micro pill b is：By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, dimension Raw element B12 and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, and the kneading time is 4~6 minutes；Granulation circle ball, granulation Speed is 0.2pm, and 0.9 millimeter of mesh size, circle ball speed is 40~50 hertz；Fluidized drying, EAT is 45~65 DEG C； Sieve to obtain the orange-yellow micropill of vitamin；
(5) preparation method of amino acid micropill b is：L-Trp, vitamin E and auxiliary material mix in proportion, prepare softwood, The kneading time is 5~10 minutes；Granulation circle ball, granulation speed is 0.2pm, and 0.9 millimeter of mesh size, circle ball speed is 40~50 Hertz；It is vacuum dried under the conditions of 50 DEG C~60 DEG C；Sieve to obtain amino acid red micropill；
(6) preparation method of vitamin C micro-pill is：Vitamin C and auxiliary material are mixed in proportion, is prepared by wetting agent with water Softwood, the kneading time is 4~6 minutes；Granulation circle ball, granulation speed is 0.2pm, and 0.9 millimeter of mesh size, circle ball speed is 50 ~60 hertz；Fluidized drying, EAT is 45~65 DEG C；Sieve to obtain vitamin C brown micropill；
(7) vitaminAD micropill：Prepared according to described in second aspect present invention any embodiment.
Method described in any embodiment according to a fourth aspect of the present invention, wherein the thiamine mononitrate micropill, vitamin The preparation method difference of micropill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b and vitamin C micro-pill this 6 kinds of micropills For：
(1) preparation method of thiamine mononitrate micropill is：Thiamine mononitrate and pharmaceutic adjuvant are mixed in proportion, is wetting with water Agent prepares softwood, and the kneading time is 4.5~5 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 55~60 hertz Hereby；Fluidized drying, 50~60 DEG C of EAT；Sieve to obtain thiamine mononitrate white micropill；
(2) preparation method of vitamin micro pill a is：Niacinamide, calcium pantothenate, vitamin B6 and auxiliary material are mixed, is with water Wetting agent prepares softwood, and the kneading time is 5~7 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 55~60 hertz Hereby；Fluidized drying, EAT is 45~65 DEG C；Sieve to obtain vitamins white micropill；
(3) preparation method of amino acid micropill a is：ILE, L-Leu, LYS, L- phenylpropyl alcohol ammonia Acid, L-threonine, Valine, METHIONINE and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, integrate the time It is 18~20 minutes, granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 45~50 hertz, under the conditions of 50 DEG C~60 DEG C Vacuum drying；Sieve to obtain amino acid yellow micropill；
(4) preparation method of vitamin micro pill b is：By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, dimension Raw element B12 and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, and the kneading time is 5~6 minutes；Granulation circle ball, screen cloth 0.9 millimeter of aperture, circle ball speed is 45~50 hertz；Fluidized drying, EAT is 50~60 DEG C；Sieve vitamin is orange Color micropill；
(5) preparation method of amino acid micropill b is：L-Trp, vitamin E and auxiliary material mix in proportion, are profit with water Humectant prepares softwood, and the kneading time is 7~9 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 45~50 hertz Hereby；It is vacuum dried under the conditions of 50 DEG C~60 DEG C；Sieve to obtain amino acid red micropill；
(6) preparation method of vitamin C micro-pill is：Vitamin C and auxiliary material are mixed in proportion, is prepared by wetting agent with water Softwood, the kneading time is 5~6 minutes；Granulation circle ball, 0.9 millimeter of mesh size, 55~60 hertz of circle ball speed；Fluidized drying, EAT is 50~65 DEG C；Sieve to obtain vitamin C brown micropill；
(7) vitaminAD micropill：Prepared according to described in second aspect present invention any embodiment.
Further, fifth aspect present invention is micro- there is provided vitaminAD described in first aspect present invention any embodiment Ball or vitaminAD micropill is preparing amino acid glue obtained in second aspect present invention any embodiment methods described Purposes in capsule, wherein component of the compound amino acid capsule comprising following part by weight：
The vitamin A and calciferol are present in the vitaminAD micropill.
Any technical characteristic in any embodiment of the present invention can be combined in any embodiment of either side, As long as this combination is not in contradiction.
In the present invention, term micropill refers to piller of the diameter between 0.05mm~1.5mm, and preferably diameter exists Piller between 0.1mm~1.2mm.This bead can be spherical or almost spherical.In the present invention, term " approximate ball Shape " refers to that the minor axis/draw ratio of piller is (0.2~1):1, preferably (0.5~1):1.In embodiments below, whole the 7 of preparation Minor axis/the draw ratio of micropill is planted, after measured, in (0.5~1):In the range of 1, the obtained vitaminAD of such as present invention is micro- Minor axis/the draw ratio of ball reaches after measured can be readily controlled in (0.9~1):In the range of 1, as noted above by adjustment Technological parameter can be readily available micropill of the average major diameter in the range of 0.2~1.2mm, can for example be readily available minor axis/ The parameters such as draw ratio, the major diameter micropill essentially identical with commercially available vitaminAD microballon.For example, it is believed that commercially available vitaminAD is micro- Pearl minor axis/draw ratio is after measured up to 0.94:1, and major diameter is between 0.4~0.6mm；This commercially available vitaminAD microballon (vitamin-AD Beads) can directly buy from the market, for example, can be bought from RIKEN CORPORATION or from Riken Vitamin Co., Ltd.s are commercially available, and the equipment registration card number of such as Riken Vitamin Co., Ltd.s import to China has H20110103 (state food and drug administration issues, trade name Riken Dry AD-B 100/10P), it is per 1g In include the unit of retinol1 00000 and the unit of calciferol 10000.The vitaminAD microballon of RIKEN CORPORATION also have with Riken Vitamin Co., Ltd. product identical performances.
The various micropills of the present invention can be used and prepared well known to a person skilled in the art method.In the present invention, except dimension Outside raw element AD micropills, other various micropills can be prepared using extrusion spheronization pill making craft.In the present invention, as do not said in addition Bright, described micropill is to prepare micropill using RE/SP series extrusion spheronization machine (Guangzhou Xi Rui plant equipment Co., Ltd product).
8 kinds of amino acid of one kind of the invention and 11 kinds of vitamin micro pill capsules are preparing treatment Chronic Liver, kidney diaseases medicine, delay Application in solution and elimination training physical fatigue food.
In the case of chronic hepatic diseases, can be effectively improved on the basis of patient's nitrogen matter excretion burden is not increased Cell promotes 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules of the biosynthesis of protein to the bioavailability of amino acid Technique uniqueness, advanced technology, the term of validity more than 3 years, product of the present invention be used for Chronic Liver, kidney and other disease treatments, alleviate and Eliminate physical fatigue.
The present invention has protrusion excellent as the enteral nutrition preparation that nitrogen source amino acid is constituted is improved in chronic disease therapy Gesture.First, it need not change the dietary structure and other treatment schemes of patient, it becomes possible to significantly improve the amino acid of patient With protein metabolism；Secondly, in the case of chronic hepatic diseases, it can not increase the basis of patient's nitrogen matter excretion burden On effectively improve bioavailability of the cell to amino acid, promote the biosynthesis of protein.It is of the invention with existing amino acid Product technology compares, and has the following advantages that：
1. reasonable mixture ratio, science, with good biological effect.Its difference and general amino acid preparation, its 8 kinds must Need the ratio of amino acid to combine Asian-Pacific area dietary protein structure, amino acid composition and absorption of human body many factors comprehensively to examine Consider and determine, wherein the large percentage of branched-chain amino acid, lysine, methionine, while adding 11 kinds of vitamins, give full play to amino Acid and the synergy of vitamin, make amino acid balanced absorption in human body, it is ensured that the bioavailability of amino acid.
2. technique is unique, advanced, using extruder grain, circle ball production technology, solves other Moriamin Forte preparations 8 kinds of essential amino acids and 11 kinds of vitamins are respectively prepared seven kinds of micropills, it is ensured that each composition by shortcoming according to different physicochemical properties Between will not chemically react and degrade in storage period, improve the stability of various active components in product.
Most amino acid are more stable in the present invention, and wherein tryptophan is easier to decompose in preparation and storage, causes Content declines.Tryptophan has indole nucleus, meets light and changes colour, and stability is poor.Tryptophan is a kind of least stable amino acid.This In 8 kinds of involved essential amino acids of invention, because L-Trp property is unstable, be not suitable for and other 7 kinds of amino acid Mixing, the present invention is that L-Trp and vitamin E are made into individually red micropill, is effectively improved the stabilization of L-Trp Property, and other 7 kinds of amino acid are made yellow micropill so that the stability of product prepared by the present invention is significantly larger than like product. The term of validity of product can be more than 3 years.
3. convenient oral.Moriamin Forte preparation in the treatment that patients with chronic diseases needs amino acid preparation for a long time, energy Enough make up some deficiencies of amino acid transfusion.The present invention is particularly suited for the chronic of Long-term taking medicine, both alleviates patient Financial burden, while improving the psychological bearing capability of patient again.
Embodiment of the present invention 1-5 gained capsules keep sample for a long time at ambient temperature respectively, respectively at 0,3,6,9,12, 18th, sample within 24,36 months, the method as described in national drug standards WS1- (X-307) -2004Z, with reference to traditional Chinese medicines in version in 2010 Two assay methods of record of allusion quotation, the sample to different time is measured indices；Result shows, various embodiments of the present invention Capsule sample kept sample through 0 month to 36 months, disintegration time limited (by official method determine) between 10~18min, 8 kinds of amino acid Content be respectively maintained in the range of the 95~107% of labelled amount within the time period of 3 years, 11 kinds of contents of vitamin are 3 Respectively it is maintained in the range of the 95~105% of labelled amount in the time period in year, shows that capsule of the present invention fully meets medicine Quality criteria requirements.
Specific embodiment
The present invention can be conducted further description by the following examples, however, the scope of the present invention is not limited In following embodiments.One of skill in the art, can be with it is understood that on the premise of without departing substantially from the spirit and scope of the present invention Various change and modification are carried out to the present invention.The present invention to used in experiment to material and test method carry out generality And/or specific description.Although for realize many materials that the object of the invention used and operating method be it is known in the art that But the present invention is still described in detail as far as possible herein.Following examples further illustrate the present invention, rather than limiting this hair It is bright.In following experiment, when preparing micropill of the present invention, vitaminAD micropill is per batch with piller gross weight meter at least 2kg's Batch is prepared, and remaining micropill is prepared per batch with the piller gross weight meter at least batch of 10kg.
Embodiment 1
The formula of 8 kinds of amino acid of the invention and 11 kinds of vitamin micro pill capsules is：Wherein thiamine mononitrate micropill, vitamin Micropill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, vitamin C micro-pill and vitaminAD micropill this seven kinds of micropills The weight ratio of circular micropill is：
Thiamine mononitrate micropill 6.88
Vitamin micro pill a 17.1
Amino acid micropill a 36.8
Vitamin micro pill b 12
Amino acid micropill b 7.56
Vitamin C micro-pill 13.4
VitaminAD micropill 6.2
1st, the formula of thiamine mononitrate micropill is：
Thiamine mononitrate 250g
Lactose 450g
Starch 45g
Calcium carboxymethylcellulose 75g
Methylcellulose 22g
Hydroxypropyl cellulose 19g
Titanium dioxide 23g
Microcrystalline cellulose 116g
2nd, the formula of vitamin micro pill a is：
Niacinamide 360g
Calcium pantothenate 100g
Vitamin B6 43g
Lactose 77g
Calcium carboxymethylcellulose 140g
Hydroxypropyl cellulose 18g
Microcrystalline cellulose 200g
Starch 83g
3rd, the formula of amino acid micropill a is
ILE 46g
L-Leu 142g
LYS 193g
L-phenylalanine 39g
L-threonine 33g
Valine 52g
METHIONINE 143g
Lactose 176g
Starch 21g
Methylcellulose 20g
Hydroxypropyl cellulose 12g
Microcrystalline cellulose 97g
Uranidin 1.6g
Calcium carboxymethylcellulose 24.4g
Lauryl sodium sulfate 15g
4th, the formula of vitamin micro pill b is：
5- hydroxyl anthranilic acid hydrochlorides 6.84g
Vitamin B2 92.4g
Folic acid 5.6g
Vitamin B12 0.028g
Lactose 441.7g
Microcrystalline cellulose 311g
Macrogol 6000 5.7g
Calcium carboxymethylcellulose 6.2g
Starch 46.8
5th, the formula of amino acid micropill b is：
L-Trp 211.8g
Vitamin E 45.6g
Lactose 252.5g
Starch 195.5g
Calcium carboxymethylcellulose 16.6g
Methylcellulose 17.85g
Hydroxypropyl cellulose 11.5g
Haematochrome 4.25g
Uranidin 0.425g
Alumina silicate 153.9g
6th, the formula of vitamin C micro-pill is：
7th, the formula rate (per 1000mg) of vitaminAD micropill is：
Retinol Palmitate 58.8mg (100,000 iu vitamin As)
Corn oil 141.2mg
Calciferol 0.25mg (10,000 iu calciferols)
Span20 10mg
Gelatin 572mg
Sodium Benzoate 0.87mg
Dehydroactic acid sodium 1.45mg
Sucrose Plus make the micropill gross weight 1000mg being made in right amount
Wherein, 7 kinds of microsphere and its preparations are respectively：
(1) thiamine mononitrate micropill is prepared：By thiamine mononitrate, lactose, starch, calcium carboxymethylcellulose, methylcellulose, hydroxyl Propyl cellulose, titanium dioxide and microcrystalline cellulose are mixed with softwood in proportion, and the kneading time is 5 minutes；Granulation circle ball, screen cloth 0.9 millimeter of aperture, circle ball speed is 60 hertz；Fluidized drying, 60 DEG C of EAT dries 3 hours；Sieve to obtain thiamine mononitrate White micropill；
(2) vitamin micro pill a is prepared：By niacinamide, calcium pantothenate, vitamin B6, lactose, calcium carboxymethylcellulose, hydroxypropyl The mixing of base cellulose, microcrystalline cellulose and starch, prepares softwood, and the kneading time is 7 minutes；Granulation circle ball, the milli of mesh size 0.9 Rice, circle ball speed is 60 hertz；Fluidized drying, EAT is 65 DEG C, dries 5 hours；Sieve vitamins white is micro- Ball；
(3) amino acid micropill a is prepared：Each material mixes in proportion, prepares softwood, and the kneading time is 20 minutes, granulation circle Ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz, is vacuum dried 15 hours under the conditions of 60 DEG C；Sieve to obtain amino acid Huang Color micropill；
(4) vitamin micro pill b is prepared：By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, vitamin B12 and Lactose, microcrystalline cellulose, Macrogol 6000, calcium carboxymethylcellulose and starch mix in proportion, prepare softwood, integrate the time It is 6 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；Fluidized drying, dries 4 hours, enters wind-warm syndrome Spend is 60 DEG C；Sieve to obtain the orange-yellow micropill of vitamin；
(5) amino acid micropill b is prepared：L-Trp, vitamin E, lactose, starch, calcium carboxymethylcellulose, Methyl cellulose Element, hydroxypropyl cellulose, haematochrome, uranidin and alumina silicate mix in proportion, prepare softwood, and the kneading time is 7 minutes；Granulation Circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；20 hours are vacuum dried under the conditions of 60 DEG C；Sieve to obtain amino Sour red micropill；
(6) vitamin C micro-pill is prepared：Each material is mixed in proportion, softwood is prepared, the kneading time is 5~6 minutes；Make Grain circle ball, 0.9 millimeter of mesh size, 60 hertz of circle ball speed；3 hours of fluidized drying, EAT is 65 DEG C；Sieving to tie up Raw element C brown micropills；
(7) vitaminAD micropill：
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (45 DEG C) are made into dissolving, Obtain oiliness liquid；It is another that gelatin and sucrose are dissolved into (75 DEG C) in water (water compares 4: 1 with gelatin weight), preservative is added, stir Mixing makes dissolving, obtains aqueous solution；
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing (65 DEG C) obtains emulsion；
(3) by step (2) gained LS (65 DEG C of fluidisations), dry (be less than 7% to loss on drying), obtain final product vitamin AD micropills.
Finally the 7 kinds of micropills for preparing are mixed in proportion, loads capsule.
Embodiment 2
The formula of 8 kinds of amino acid of the invention and 11 kinds of vitamin micro pill capsules is：
Wherein thiamine mononitrate micropill, vitamin micro pill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, dimension life The weight ratio of plain C micropills and vitaminAD micropill this seven kinds of micropills circle micropills is：
Thiamine mononitrate micropill 2.66
Vitamin micro pill a 16.35
Amino acid micropill a 35.0
Vitamin micro pill b 11.4
Amino acid micropill b 6.65
Vitamin C micro-pill 12.73
VitaminAD micropill 5.7
1st, the formula of thiamine mononitrate micropill is：
Thiamine mononitrate 76g
Lactose 225g
Starch 9g
Calcium carboxymethylcellulose 15g
Methylcellulose 4.4g
Hydroxypropyl cellulose 3.8g
Titanium dioxide 4.6g
Microcrystalline cellulose 58g
2nd, the formula of vitamin micro pill a is：
Niacinamide 245g
Calcium pantothenate 62g
Vitamin B6 31g
Lactose 19.4g
Calcium carboxymethylcellulose 56g
Hydroxypropyl cellulose 3.6g
Microcrystalline cellulose 93.5g
Starch 16.6g
3rd, the formula of amino acid micropill a is：
4th, the formula of vitamin micro pill b is：
5- hydroxyl anthranilic acid hydrochlorides 3.6g
Vitamin B2 44g
Folic acid 3.6g
Vitamin B12 0.018g
Lactose 255g
Microcrystalline cellulose 157.5g
Macrogol 6000 1.7g
Calcium carboxymethylcellulose 1.84g
Starch 13.97g
5th, the formula of amino acid micropill b is：
L-Trp 151g
Vitamin E 31g
Lactose 148.5g
Starch 115g
Calcium carboxymethylcellulose 3.9g
Methylcellulose 4.2g
Hydroxypropyl cellulose 2.6g
Haematochrome 1g
Uranidin 0.1g
Alumina silicate 38.2g
6th, ascorbic formula is：
Vitamin C 315g
Lactose 135.5g
Starch 12.06g
Microcrystalline cellulose 15.12g
Calcium carboxymethylcellulose 9g
Macrogol 6000 7.6g
Methylcellulose 3.6g
Chocolate pigment 0.58g
Hydroxypropyl cellulose 10g
Citric acid 10g
7th, the formula rate (per 1000mg) of vitaminAD micropill is：
Vitamine A acetate Equivalent 150,000 VA
Soybean oil 120mg
Calciferol
Span40 2mg
Gelatin 400mg
Mud parker methyl ester 0.75mg
Mud moor gold ethyl ester 0.5mg
Sucrose Plus make the micropill gross weight 1000mg being made in right amount
Wherein, 7 kinds of microsphere and its preparations are respectively：
(1) thiamine mononitrate micropill is prepared：Thiamine mononitrate and pharmaceutic adjuvant are mixed with softwood in proportion, the kneading time is 4.5 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 550 hertz；Fluidized drying 5 hours, EAT 50~ 60℃；Sieve to obtain thiamine mononitrate white micropill；
(2) vitamin micro pill a is prepared：Niacinamide, calcium pantothenate, vitamin B6 and auxiliary material are mixed, softwood is prepared, during kneading Between be 6 clocks；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 55~60 hertz；Fluidized drying 4 hours, EAT It is 60 DEG C；Sieve to obtain vitamins white micropill；
(3) amino acid micropill a is prepared：ILE, L-Leu, LYS, L-phenylalanine, L- Soviet Unions ammonia Acid, Valine, METHIONINE and auxiliary material mix in proportion, prepare softwood, and the kneading time is 18 minutes, granulation circle ball, sieve 0.9 millimeter of screen distance, circle ball speed is 4 hertz, is vacuum dried 20 hours under the conditions of 60 DEG C；Sieve amino acid yellow is micro- Ball；
(4) vitamin micro pill b is prepared：By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, vitamin B12 and Auxiliary material mixes in proportion, prepares softwood, and the kneading time is 6 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 45 Hertz；Fluidized drying 3 hours, EAT is 50 DEG C；Sieve to obtain the orange-yellow micropill of vitamin；
(5) amino acid micropill b is prepared：L-Trp, vitamin E and auxiliary material mix in proportion, prepare softwood, integrate the time It is 8 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；It is vacuum dried 20 hours under the conditions of 60 DEG C； Sieve to obtain amino acid red micropill；
(6) vitamin C micro-pill is prepared：Vitamin C and auxiliary material are mixed in proportion, softwood is prepared, the kneading time is 5 points Clock；Granulation circle ball, 0.9 millimeter of mesh size, 60 hertz of circle ball speed；Fluidized drying 5 hours, EAT is 60 DEG C；Sieving Obtain vitamin C brown micropill；
(7) vitaminAD micropill：
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (35 DEG C) are made into dissolving, Obtain oiliness liquid；It is another that by gelatin and sucrose dissolving (100 DEG C), in water, (water compares 2 with gelatin weight：1) in, preservative is added, is stirred Mixing makes dissolving, obtains aqueous solution；
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing (100 DEG C) obtains emulsion；
(3) by step (2) gained LS (30 DEG C of fluidisations), dry (be less than 7% to loss on drying), obtain final product vitamin AD micropills.
Finally the 7 kinds of micropills for preparing are mixed in proportion, loads capsule.
Embodiment 3
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules is：
Thiamine mononitrate micropill, vitamin micro pill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, vitamin C The weight ratio of micropill and vitaminAD micropill this seven kinds of micropills circle micropills is：
Thiamine mononitrate micropill 9.9
Vitamin micro pill a 20.5
Amino acid micropill a 44.1
Vitamin micro pill b 14.4
Amino acid micropill b 10.5
Vitamin C micro-pill 16.0
VitaminAD micropill 9.36
1st, the formula of thiamine mononitrate micropill is：
2nd, the formula of vitamin micro pill a is：
Niacinamide 580g
Calcium pantothenate 145g
Vitamin B6 72g
Lactose 174.6g
Calcium carboxymethylcellulose 168g
Hydroxypropyl cellulose 32.4g
Microcrystalline cellulose 280.5g
Starch 149.4g
3rd, the formula of amino acid micropill a is：
ILE 80g
L-Leu 248g
LYS 338g
L-phenylalanine 67g
L-threonine 56g
Valine 90g
METHIONINE 245g
Lactose 264g
Starch 37.8g
Methylcellulose 36g
Hydroxypropyl cellulose 21.6g
Microcrystalline cellulose 174.6g
Uranidin 2.88g
Calcium carboxymethylcellulose 43.92g
Lauryl sodium sulfate 30g
4th, the formula that vitamin micro pill b is included is：
5- hydroxyl anthranilic acid hydrochlorides 8.3g
Vitamin B2 124g
Folic acid 8.3g
Vitamin B12 0.04g
Lactose 765g
Microcrystalline cellulose 472.5g
Macrogol 6000 15.3g
Calcium carboxymethylcellulose 16.56g
Starch 125.77g
5th, amino acid micropill b is included in parts by weight：
L-Trp 284g
Vitamin E 56g
Lactose 445.5g
Starch 345g
Calcium carboxymethylcellulose 35.1g
Methylcellulose 37.8g
Hydroxypropyl cellulose 23.4g
Haematochrome 9g
Uranidin 0.9g
Alumina silicate 271.5g
6th, the formula of vitamin C micro-pill is：
Vitamin C 745g
Lactose 406.5g
Starch 108.5g
Microcrystalline cellulose 136.08g
Calcium carboxymethylcellulose 81g
Macrogol 6000 68.4g
Methylcellulose 32.4g
Chocolate pigment 5.22g
Hydroxypropyl cellulose 50g
Citric acid 50g
7th, the formula rate (per 1000mg) of vitaminAD micropill is：
Vitamin A Equivalent 50,000 VA
Peanut oil 160mg
Calciferol
Span60 20mg
Gelatin 700mg
Sorbic acid 0.65mg
Potassium sorbate 1mg
Sucrose Plus make the micropill gross weight 1000mg being made in right amount
Wherein, 7 kinds of microsphere and its preparations are respectively：
(1) thiamine mononitrate micropill is prepared：Thiamine mononitrate and pharmaceutic adjuvant are mixed with softwood in proportion, the time 6 is integrated Minute；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 60 hertz；Fluidized drying 4 hours, 65 DEG C of EAT；Cross Sieve to obtain thiamine mononitrate white micropill；
(2) vitamin micro pill a is prepared：Niacinamide, calcium pantothenate, vitamin B6 and auxiliary material are mixed, softwood is prepared, during kneading Between be 8 minutes；Granulation circle ball, 0.9 millimeter of mesh size, 560 hertz of circle ball speed；Fluidized drying 3 hours, EAT is 65 ℃；Sieve to obtain vitamins white micropill；
(3) amino acid micropill a is prepared：By ILE, L-Leu, LYS, L-phenylalanine, L- Soviet Unions Propylhomoserin, Valine, METHIONINE and auxiliary material mix in proportion, prepare softwood, and the kneading time is 20 minutes, granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz, is vacuum dried 15 hours under the conditions of 60 DEG C；Sieve to obtain amino acid yellow Micropill；
(4) vitamin micro pill b is prepared：By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, vitamin B12 and Auxiliary material mixes in proportion, prepares softwood, and the kneading time is 6 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 Hertz；Fluidized drying 5 hours, EAT is 65 DEG C；Sieve to obtain the orange-yellow micropill of vitamin；
(5) amino acid micropill b is prepared：L-Trp, vitamin E and auxiliary material mix in proportion, prepare softwood, integrate the time It is 10 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；Vacuum drying 15 is small under the conditions of 60 DEG C When；Sieve to obtain amino acid red micropill；
(6) vitamin C micro-pill is prepared：Vitamin C and auxiliary material are mixed in proportion, softwood is prepared, the kneading time is 6 points Clock；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 60 hertz；Fluidized drying 4 hours, EAT is 65 DEG C；Cross Sieve to obtain vitamin C brown micropill；
(7) vitaminAD micropill：
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (100 DEG C) are made into dissolving, Obtain oiliness liquid；It is another that by gelatin and sucrose dissolving (40 DEG C), in water, (water compares 6 with gelatin weight：1) in, preservative is added, is stirred Mixing makes dissolving, obtains aqueous solution；
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing (50 DEG C) obtains emulsion；
(3) by step (2) gained LS (- 25 DEG C of liquid nitrogen atmosphere/fluidisation/distillations), talcum powder is added (to account for final gained VitaminAD micropill weight 0.2%), dry (to loss on drying be less than 7%), obtain final product vitaminAD micropill.
Finally the 7 kinds of micropills for preparing are mixed in proportion, loads capsule.
Embodiment 4
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules is：
Thiamine mononitrate micropill, vitamin micro pill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, vitamin C The weight ratio of micropill and vitaminAD micropill this seven kinds of micropills circle micropills is：
Thiamine mononitrate micropill 47.7
Vitamin micro pill a 167.2
Amino acid micropill a 358.8
Vitamin micro pill b 117
Amino acid micropill b 70.05
Vitamin C micro-pill 130.65
VitaminAD micropill 60.9
1st, the formula of thiamine mononitrate micropill is：(unit：Kilogram)
Thiamine mononitrate 16.3
Lactose 33.75
Starch 2.7
Calcium carboxymethylcellulose 4.5
Methylcellulose 1.32
Hydroxypropyl cellulose 1.14
Titanium dioxide 1.38
Microcrystalline cellulose 8.7
2nd, the formula of vitamin micro pill a is：(unit：Kilogram)
Niacinamide 30.25
Calcium pantothenate 8.1
Vitamin B6 3.7
Lactose 4.1
Calcium carboxymethylcellulose 11.8
Hydroxypropyl cellulose 0.76
Microcrystalline cellulose 19.73
Starch 3.5
3rd, the formula of amino acid micropill a is：(unit：Kilogram)
4th, the formula of vitamin micro pill b is：(unit：Kilogram)
5- hydroxyl anthranilic acid hydrochlorides 0.465
Vitamin B2 6.05
Folic acid 0.415
Vitamin B12 0.002
Lactose 38.25
Microcrystalline cellulose 23.625
Macrogol 6000 0.51
Calcium carboxymethylcellulose 0.552
Starch 4.19215
5th, the formula of amino acid micropill b is：(unit：Kilogram)
L-Trp 17.1
Vitamin E 3.65
Lactose 22.275
Starch 17.25
Calcium carboxymethylcellulose 1.17
Methylcellulose 1.26
Hydroxypropyl cellulose 0.78
Haematochrome 0.3
Uranidin 0.03
Alumina silicate 13.575
6th, the formula of vitamin C micro-pill is：(unit：Kilogram)
Vitamin C 38.9
Lactose 20.325
Starch 3.618
Microcrystalline cellulose 4.536
Calcium carboxymethylcellulose 2.7
Macrogol 6000 2.28
Methylcellulose 1.08
Chocolate pigment 0.174
Hydroxypropyl cellulose 1.572
Citric acid 2
7th, the formula rate (per 1000mg) of vitaminAD micropill is：
Retinol Palmitate Equivalent 20,000 VA
Sunflower oil 100mg
Calciferol
Span80 15mg
Gelatin 500mg
Sodium Benzoate 1mg
Sucrose Plus make the micropill gross weight 1000mg being made in right amount
Wherein, 7 kinds of microsphere and its preparations are respectively：
(1) thiamine mononitrate micropill is prepared：Thiamine mononitrate and pharmaceutic adjuvant are mixed with softwood in proportion, the time 4 is integrated Minute；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；Fluidized drying 3 hours, 65 DEG C of EAT；Cross Sieve to obtain thiamine mononitrate white micropill；
(2) vitamin micro pill a is prepared：Niacinamide, calcium pantothenate, vitamin B6 and auxiliary material are mixed, softwood is prepared, during kneading Between be 4 minutes；Granulation circle ball, 0.9 millimeter of mesh size, 50 hertz of circle ball speed；Fluidized drying 3 hours, EAT is 45 ℃；Sieve to obtain vitamins white micropill；
(3) amino acid micropill a is prepared：By ILE, L-Leu, LYS, L-phenylalanine, L- Soviet Unions Propylhomoserin, Valine, METHIONINE and auxiliary material mix in proportion, prepare softwood, and the kneading time is 15 minutes, granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 40 hertz, is vacuum dried 17 hours under the conditions of 50 DEG C；Sieve to obtain amino acid yellow Micropill；
(4) vitamin micro pill b is prepared：By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, vitamin B12 and Auxiliary material mixes in proportion, prepares softwood, and the kneading time is 4 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 40 Hertz；Fluidized drying 5 hours, EAT is 45 DEG C；Sieve to obtain the orange-yellow micropill of vitamin；
(5) amino acid micropill b is prepared：L-Trp, vitamin E and auxiliary material mix in proportion, prepare softwood, integrate the time It is 5 minutes；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 40 hertz；It is vacuum dried 18 hours under the conditions of 50 DEG C； Sieve to obtain amino acid red micropill；
(6) vitamin C micro-pill is prepared：Vitamin C and auxiliary material are mixed in proportion, softwood is prepared, the kneading time is 4~6 Minute；Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；Fluidized drying 3 hours, EAT is 45 DEG C； Sieve to obtain vitamin C brown micropill；
(7) vitaminAD micropill：
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (80 DEG C) are made into dissolving, Obtain oiliness liquid；It is another that by gelatin and sucrose dissolving (50 DEG C), in water, (water compares 3 with gelatin weight：1) in, preservative is added, is stirred Mixing makes dissolving, obtains aqueous solution；
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing (60 DEG C) obtains emulsion；
(3) by step (2) gained LS (- 35 DEG C of liquid nitrogen atmosphere/fluidisation/distillations), drying (is less than to loss on drying 7%) silica (accounting for the 0.1% of final gained vitaminAD micropill weight) is added during, vitaminAD micropill is obtained final product.
Finally the 7 kinds of micropills for preparing are mixed in proportion, loads capsule.
Embodiment 5
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules is：
Thiamine mononitrate micropill, vitamin micro pill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, vitamin C The weight ratio of micropill and vitaminAD micropill this seven kinds of micropills circle micropills is：
Thiamine mononitrate micropill 8.4
Vitamin micro pill a 18.83
Amino acid micropill a 40.48
Vitamin micro pill b 13.2
Amino acid micropill b 8.96
Vitamin C micro-pill 14.74
VitaminAD micropill 7.92
1st, the formula of thiamine mononitrate micropill bag is：(unit：Kilogram)
Thiamine mononitrate 27.5
Lactose 56.25
Starch 6.3
Calcium carboxymethylcellulose 10.5
Methylcellulose 3.08
Hydroxypropyl cellulose 2.66
Titanium dioxide 3.22
Microcrystalline cellulose 14.5
2nd, the formula of vitamin micro pill a is：(unit：Kilogram)
Niacinamide 47
Calcium pantothenate 12.25
Vitamin B6 5.75
Lactose 16.76
Calcium carboxymethylcellulose 16.1
Hydroxypropyl cellulose 3.0
Microcrystalline cellulose 25
Starch 14
3rd, the formula of amino acid micropill a is：(unit：Kilogram)
ILE 6.3
L-Leu 19.5
LYS 26.55
L-phenylalanine 5.3
L-threonine 4.45
Valine 7.1
METHIONINE 19.4
Lactose 22
Starch 2.94
Methylcellulose 2.8
Hydroxypropyl cellulose 1.68
Microcrystalline cellulose 13.58
Uranidin 0.224
Calcium carboxymethylcellulose 3.416
Lauryl sodium sulfate 2.5
4th, the formula of vitamin micro pill b is：(unit：Kilogram)
5- hydroxyl anthranilic acid hydrochlorides 0.7
Vitamin B2 10.05
Folic acid 0.65
Vitamin B12 0.003
Lactose 63.75
Microcrystalline cellulose 39.375
Macrogol 6000 1.19
Calcium carboxymethylcellulose 1.288
Starch 9.78215
5th, the formula of amino acid micropill b is：(unit：Kilogram)
6th, the formula of vitamin C micro-pill is：(unit：Kilogram)
Vitamin C 60.4
Lactose 33.875
Starch 8.44
Microcrystalline cellulose 10.584
Calcium carboxymethylcellulose 6.3
Macrogol 6000 5.32
Methylcellulose 2.52
Chocolate pigment 0.406
Hydroxypropyl cellulose 3.668
Citric acid 4
7th, the formula rate (per 1000mg) of vitaminAD micropill is：
Vitamine A acetate Equivalent 200,000 VA
Corn oil 200mg
Calciferol
Span40 12mg
Gelatin 650mg
Dehydroactic acid sodium 3mg
Sucrose Plus make the micropill gross weight 1000mg being made in right amount
Wherein, preceding 6 kinds of microsphere and its preparations are referring to embodiment 1, and vitaminAD micropill preparation method is as follows：
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (55 DEG C) are made into dissolving, Obtain oiliness liquid；It is another that by gelatin and sucrose dissolving (85 DEG C), in water, (water compares 5 with gelatin weight：1) in, preservative is added, is stirred Mixing makes dissolving, obtains aqueous solution；
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing (80 DEG C) obtains emulsion；
(3) by step (2) gained LS (- 45 DEG C of liquid nitrogen atmosphere/fluidisation/distillations), drying (is less than to loss on drying 7%) magnesium stearate (accounting for the 0.2% of final gained vitaminAD micropill weight) is added after, drying, vitaminAD micropill is obtained final product.
Finally the 7 kinds of micropills for preparing are mixed in proportion, loads capsule.
Test example 1：
In the various embodiments described above, make wherein gained vitamin micro pill a with vitaminAD micropill according to capsule formula respectively In the mixing of the two ratio, then the mixture is put 40 DEG C of placement June, vitamin A contains when determining 0 month and during June in mixture Amount and vitamin D content (are surveyed according to method contained in Chinese Pharmacopoeia two vitaminAD soft capsules of version in 2015 or drops respectively It is fixed), for vitamin A or D in per a collection of biased sample, during with its June content divided by content at 0 month multiplied by with 100% institute Obtain percentage, the remaining percentage that vitamin A or D are postponed at through 40 DEG C-June in as this batch mixture；Result shows, right Mix gained mixture with vitaminAD micropill in vitamin micro pill a obtained in example 1 above -5, their vitamin A is residual In the range of 97.3~99.0%, vitamin D remnants percentages show this to remaining percentage in the range of 97.6~99.3% Vitamin A and D in a little mixtures are respectively provided with excellent stability；In addition, including 8 kinds of amino to embodiment 1-5 gained simultaneously Acid and 11 kinds of vitamin micro pill capsule agent carry out above-mentioned 40 DEG C-June dispose and determine vitamin A, D remnants percentages, as a result tie up In the range of 97.5~99.4%, vitamin D remnants percentages are in 97.6~99.2% scopes for raw element A remnants percentages It is interior；This shows, vitaminAD micropill individually with vitamin micro pill a or when jointly mixing with remaining 6 kinds of micropill, wherein tieing up The stability of raw element A, D is presented essentially identical result.Then, the vitaminAD microballon produced purchased from RIKEN CORPORATION is used (Riken Dry AD-B 100/10P, by Riken Vitamin Co., Ltd.'s imports to China, contain in every 1 gram of microballon Vitamin A is 10 million international units, and the plain element D2 of dimension is 1 million international units), it is micro- with the gained vitamin of example 1 above -5 respectively Ball a is according to the two ratio mixing in capsule formula, then the mixture is put 40 DEG C of placement June, mixed when determining 0 month and during June Vitamin A content and vitamin D content are (respectively according to Chinese Pharmacopoeia two vitaminAD soft capsules of version in 2015 or drops in compound In contained method determine), for vitamin A or D in per a collection of biased sample, content is divided by content at 0 month during with its June Multiplied by with 100% gained percentage, the remaining percentage that vitamin A or D are postponed at through 40 DEG C-June in as this batch mixture Number；Result shown, institute is mixed with Riken Dry AD-B 100/10P for vitamin micro pill a obtained in example 1 above -5 Mixture is obtained, in the range of 86.6~89.4%, vitamin D remnants percentages exist their vitamin A remnants percentages In the range of 83.6~88.7%, show that vitamin A and D stability in these mixtures are undesirable；In addition, making the Riken Dry AD-B 100/10P such as replace at the vitaminAD micropill in the embodiment 1-5 of weight respectively, capsule are made, while carrying out 40 DEG C-June disposes and determines vitamin A, D remnants percentages, and as a result vitamin A remnants percentages are in 87.1~88.9% models In enclosing, vitamin D remnants percentages are in the range of 84.6~89.3%；This shows, commercially available Riken Dry AD-B 100/ 10P individually with vitamin micro pill a or when jointly mixing with remaining 6 kinds of micropill, wherein vitamin A, the stability of D are paid no attention to Think.Followed by according to the method for disposal of above-mentioned 40 DEG C-June, the five kinds of vitaminADs investigated obtained by embodiment of the present invention 1-5 are micro- The stability of ball and commercially available Riken Dry AD-B100/10P, determines their vitamin A remnants percentages and Wei Sheng respectively Plain D remnants percentages, as a result show that the vitamin A remnants percentages and vitamin D of this 6 batches of vitaminAD micropill/microballons are remaining Percentage is in the range of 97.7~99.4%.In this experiment in the remaining percentage of vitamin A or vitamin D and following experiment " labelled amount " has different implications, and the two is with reference to difference from without positive connection.
Comprising 8 kinds of amino acid and 11 kinds of loaded national drug standards of vitamin micro pill capsule agent, its standard No. is WS1- (X-307) -2004Z, the standard is applied to the present invention and includes 8 kinds of amino acid and 11 kinds of vitamin micro pill capsule agent, and is applicable VitaminAD micropill replaces with Japan's reason and grinds the capsule produced obtained by vitaminAD microballon in capsule of the present invention；In the present invention Literary embodiment 1-5 gained capsule shines the standard detection, it has been found that indices meet standard regulation.
Test example 2：
In the present invention, term micropill refers to piller of the diameter between 0.05mm~1.5mm, and preferably diameter exists Piller between 0.1mm~1.2mm.This bead can be spherical or almost spherical.In the present invention, term " approximate ball Shape " refers to that the minor axis/draw ratio of piller is (0.2~1):1, preferably (0.5~1):1.In embodiment hereof 1-5, preparation it is complete Minor axis/the draw ratio of 7 kinds of portion micropill, after measured, in (0.5~1):In the range of 1, the obtained vitaminAD of such as present invention Minor axis/the draw ratio of micropill reaches after measured can be readily controlled in (0.9~1):In the range of 1, as noted above by tune Whole technological parameter can be readily available micropill of the average major diameter in the range of 0.2~1.2mm, for example, can be readily available short The parameters such as footpath/draw ratio, the major diameter micropill essentially identical with commercially available vitaminAD microballon.For example, it is believed that commercially available vitamin AD microballons minor axis/draw ratio is after measured up to 0.94:1, and major diameter is between 0.4~0.6mm.
As described above, the present invention can be readily available averagely when vitaminAD micropill is prepared by adjusting process parameter Particle diameter in 200~1200 μ ms, particularly micropill of its average grain diameter in 300~900 μ ms.For example, by step Suddenly the intensity adjustment of emulsification procedure can obtain desired average grain diameter in (2), such as can obtain flat when emulsion strength is high The smaller micropill of equal particle diameter, and the average grain diameter of gained micropill is than larger when emulsion strength is relatively low.With average grain diameter ± Micropill number in the range of 50 μm accounts for the percentage of total micropill number for index to judge the width of micropill size distribution, and display is real In applying each processing step that vitaminAD micropill is prepared in a 1-5, technological parameter therein is made to meet present invention provide that it is suitable After adjustment, this percentage is all higher than 70%, and both greater than 80% particularly in the case of the overwhelming majority, this performance shows this hair Bright micropill has very narrow particle size distribution.
When example 1 above -5 prepares vitaminAD micropill, by the drying of step (3), can cause described micro- Moisture (in terms of 105 DEG C of dryings, 2 hours gained loss on drying results) in ball is respectively less than 7%.In addition, the inventive method system Standby vitaminAD micropill, does not use organic solvent, in the absence of the problem of organic solvent residual.

Claims (10)

1. a kind of vitaminAD micropill, wherein comprising vitamin A and calciferol；2~200,000 I.U. are included in its every 1 gram of micropill Vitamin A, 0.2~20,000 I.U. vitamin Ds2。
2. vitaminAD micropill according to claim 1, it is characterised in that：
5~150,000 I.U. vitamin As are included in its every 1 gram of micropill；
8~120,000 I.U. vitamin As are included in its every 1 gram of micropill；
100,000 I.U. vitamin As are included in its every 1 gram of micropill；
0.5~1.5 ten thousand I.U. vitamin Ds are included in its every 1 gram of micropill2；
0.8~1.2 ten thousand I.U. vitamin Ds are included in its every 1 gram of micropill2；
10,000 I.U. vitamin Ds are included in its every 1 gram of micropill2；And/or
The vitamin A be with vitamin A or Retinol Palmitate or vitamine A acetate or vitamin A its The form of its ester is added in the vitaminAD micropill.
3. vitaminAD micropill according to claim 1, it is characterised in that：
Wherein also contain edible vegetable oil such as corn oil, soybean oil, peanut oil, sunflower oil etc.；
100~200mg of edible vegetable oil, such as such as 120~160mg, 130~150mg are included in its every 1 gram of micropill；
Wherein also contain sorbitan fatty acid ester, such as span20 (i.e. Arlacel-20), span40 (i.e. Arlacel-40), Span60 (i.e. Arlacel-60), span65 (i.e. Arlacel-65), span80 (i.e. Arlacel-80), span85 (i.e. Arlacel-85)；
2~20mg of sorbitan fatty acid ester, such as such as 2~15mg, 2~12mg are included in its every 1 gram of micropill；
Wherein also contain gelatin；
400~700mg of gelatin, such as such as 500~650mg, 550~600mg are included in its every 1 gram of micropill；
Wherein also contain sucrose；
100~300mg of sucrose, such as such as 150~250mg, 180~240mg are included in its every 1 gram of micropill；
Wherein also contain preservative；In one embodiment, the preservative is selected from Sodium Benzoate, dehydroactic acid sodium, sorb Acid, potassium sorbate, mud parker methyl ester, mud moor gold ethyl ester, the golden propyl ester of mud pool and combinations thereof；
1~5mg of anti-corrosion, such as such as 1.5~3mg, 2~3mg are included in its every 1 gram of micropill；
Wherein contain Sodium Benzoate, 0.2~2mg of Sodium Benzoate, such as 0.5~1.5mg, such as 0.75 are included in every 1 gram of micropill ~1mg；And/or
Wherein contain dehydroactic acid sodium, in every 1 gram of micropill comprising 0.5~5mg of dehydroactic acid sodium, such as 1~3mg, such as 1.2~ 2mg。
4. vitaminAD micropill according to claim 1, it is prepared according to the method for comprising the following steps：
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing are made into dissolving, obtains oiliness liquid； Separately gelatin and sucrose are dissolved in the water, preservative is added, is stirred to dissolve, obtain aqueous solution；
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing obtains emulsion；
(3) by step (2) gained LS, dry, obtain vitaminAD micropill.
5. vitaminAD micropill according to claim 1, it is characterised in that：
In step (1), described oiliness liquid is obtained at a temperature of 35~100 DEG C, is made e.g. at a temperature of 35~80 DEG C ；
In step (1), described aqueous solution is obtained at a temperature of 40~100 DEG C, is made e.g. at a temperature of 50~85 DEG C ；
The temperature that step (2) medium oil liquid mixes with aqueous solution is 50~100 DEG C, such as 60~80 DEG C；
Spray drying described in step (3) is to make LS to temperature be less than in 70 DEG C of environment and dry to make to form particulate；
Spray drying described in step (3) is to make in LS to the environment of 20~70 DEG C of temperature and drying makes to form particulate；
Spray drying described in step (3) is to make to make shape in LS to the environment of 20~70 DEG C of temperature and through fluidized bed drying Into particulate；
Spray drying described in step (3) is to make LS then (optional in fluidisation less than in -20 DEG C of environment to temperature Under state) make into particulate through lyophilization；
Spray drying described in step (3) is to make LS then (optional in fluidisation less than in -30 DEG C of environment to temperature Under state) make into particulate through lyophilization；
Spray drying described in step (3) is to make LS then (optional in fluidisation less than in -40 DEG C of environment to temperature Under state) make into particulate through lyophilization；
Environment of the temperature described in step (3) less than -20 DEG C is space environment to be carried out by using liquid nitrogen cool down acquisition；
Wherein also include lubricant；
Described lubricant is added before micropill drying, during drying or after drying；
The lubricant is selected from magnesium stearate, stearic acid, calcium stearate, talcum powder, silica, molecular weight 4000-6000 Polyethylene glycol etc. and combinations thereof；And/or
The lubricant accounts for 0.005~1%, such as the 0.1~0.5% of the vitaminAD micropill weight after drying.
6. vitaminAD micropill according to claim 1, it is characterised in that：
Its moisture, less than 10%, is, for example, less than 7% in terms of loss on drying；The loss on drying is in 105 DEG C of dryings 2 hours What measure was obtained；
In 200~1200 μ ms, particularly its average grain diameter is in 300~900 μ ms for its average grain diameter；And/or
Micropill number wherein in the range of average grain diameter ± 50 μm accounts for more than the 60% of total micropill number, for example, account for total micropill number More than 70%, for example account for more than the 80% of total micropill number.
7. the method for preparing vitaminAD micropill, it comprises the following steps：
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing are made into dissolving, obtains oiliness liquid； Separately gelatin and sucrose are dissolved in the water, preservative is added, is stirred to dissolve, obtain aqueous solution；
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing obtains emulsion；
(3) by step (2) gained LS, dry, obtain vitaminAD micropill.
8. method according to claim 7, it is characterised in that：
2~200,000 I.U. vitamin As are included in every 1 gram of the vitaminAD micropill, such as 5~15 are included in its every 1 gram of micropill 8~120,000 I.U. vitamin As are included in ten thousand I.U. vitamin As, such as its every 1 gram of micropill, such as 10 are included in its every 1 gram of micropill Ten thousand I.U. vitamin As；
The vitamin A be with vitamin A or Retinol Palmitate or vitamine A acetate or vitamin A its The form of its ester is added in the vitaminAD micropill；
0.2~20,000 I.U. vitamin Ds are included in every 1 gram of the vitaminAD micropill2, such as in its every 1 gram of micropill comprising 0.5~ 1.5 ten thousand I.U. vitamin Ds2, such as 0.8~1.2 ten thousand I.U. vitamin Ds are included in its every 1 gram of micropill2, such as its every 1 gram of micropill In include 10,000 I.U. vitamin Ds2；
The edible vegetable oil such as corn oil, soybean oil, peanut oil, sunflower oil etc.；
In every 1 gram of the vitaminAD micropill comprising 100~200mg of edible vegetable oil, such as 120~160mg, such as 130~ 150mg；
The sorbitan fatty acid ester, such as span20, span40, span60, span65, span80, span85；
In every 1 gram of the vitaminAD micropill comprising 2~20mg of sorbitan fatty acid ester, such as 2~15mg, such as 2~ 12mg；
400~700mg of gelatin, such as such as 500~650mg, 550~600mg are included in every 1 gram of the vitaminAD micropill；
100~300mg of sucrose, such as such as 150~250mg, 180~240mg are included in every 1 gram of the vitaminAD micropill；
The preservative be selected from Sodium Benzoate, dehydroactic acid sodium, sorbic acid, potassium sorbate, mud parker methyl ester, mud moor gold ethyl ester, Golden propyl ester of mud pool and combinations thereof；
1~5mg of preservative, such as such as 1.5~3mg, 2~3mg are included in every 1 gram of the vitaminAD micropill；
0.2~2mg of Sodium Benzoate, such as such as 0.5~1.5mg, 0.75~1mg are included in every 1 gram of the vitaminAD micropill；
0.5~5mg of dehydroactic acid sodium, such as such as 1~3mg, 1.2~2mg are included in every 1 gram of the vitaminAD micropill；
In step (1), described oiliness liquid is obtained at a temperature of 35~100 DEG C, is made e.g. at a temperature of 35~80 DEG C ；
In step (1), described aqueous solution is obtained at a temperature of 40~100 DEG C, is made e.g. at a temperature of 50~85 DEG C ；
The temperature that step (2) medium oil liquid mixes with aqueous solution is 50~100 DEG C, such as 60~80 DEG C；
Spray drying described in step (3) is to make LS to temperature be less than in 70 DEG C of environment and dry to make to form particulate；
Spray drying described in step (3) is to make in LS to the environment of 20~70 DEG C of temperature and drying makes to form particulate；
Spray drying described in step (3) is to make to make shape in LS to the environment of 20~70 DEG C of temperature and through fluidized bed drying Into particulate；
Spray drying described in step (3) is to make LS then (optional in fluidisation less than in -20 DEG C of environment to temperature Under state) make into particulate through lyophilization；
Spray drying described in step (3) is to make LS then (optional in fluidisation less than in -30 DEG C of environment to temperature Under state) make into particulate through lyophilization；
Spray drying described in step (3) is to make LS then (optional in fluidisation less than in -40 DEG C of environment to temperature Under state) make into particulate through lyophilization；
Environment of the temperature described in step (3) less than -20 DEG C is space environment to be carried out by using liquid nitrogen cool down acquisition；
The dry moisture being so that in the micropill is, for example, less than less than 10% in terms of loss on drying described in step (3) 7%；The loss on drying is determined and obtained for 2 hours in 105 DEG C of dryings；
In 200~1200 μ ms, particularly its average grain diameter is 300 for vitaminAD micropill its average grain diameter obtained by it In~900 μ ms；And/or
VitaminAD micropill obtained by it, wherein the micropill number in the range of average grain diameter ± 50 μm accounts for total micropill number More than 60%, more than the 70% of total micropill number is for example accounted for, for example account for more than the 80% of total micropill number.
9. a kind of capsule, it includes 7 kinds of spherical or almost spherical micropills, and wraps up the capsule shells of these micropills, described 7 8 kinds of amino acid and 11 kinds of vitamins are included in kind micropill, and 7 kinds of micropills and its weight proportion are in parts by weight：
Wherein：
The vitaminAD micropill is as described in claim any one of 1-6, or as described in claim any one of 7-8 Obtained in method；
Described thiamine mononitrate micropill is included in parts by weight：
Described vitamin micro pill a is included in parts by weight：
Described amino acid micropill a is included in parts by weight：
Described vitamin micro pill b is included in parts by weight：
Described amino acid micropill b is included in parts by weight：
Described vitamin C micro-pill is included in parts by weight：
10. obtained in vitaminAD micropill described in any one of claim 1-6, or claim 7-8 any one methods describeds Purposes of the vitaminAD micropill in compound amino acid capsule is prepared, wherein the compound amino acid capsule includes following weight ratio The component of example：
The vitamin A and calciferol are present in the vitaminAD micropill.
CN201710194040.8A 2017-03-28 2017-03-28 Method for preparing vitamin AD micro-pills and compound amino acid capsule composition thereof Active CN106821998B (en)

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