CN106902100B - VitaminAD pellet and compound amino acid capsule composition comprising it - Google Patents

VitaminAD pellet and compound amino acid capsule composition comprising it Download PDF

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Publication number
CN106902100B
CN106902100B CN201710194320.9A CN201710194320A CN106902100B CN 106902100 B CN106902100 B CN 106902100B CN 201710194320 A CN201710194320 A CN 201710194320A CN 106902100 B CN106902100 B CN 106902100B
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pellet
vitamin
vitaminad
amino acid
oil
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CN106902100A (en
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马俊
彭潇波
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
    • 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
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—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
    • A61K9/14—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
    • 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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Abstract

The present invention relates to vitaminAD pellet and include its compound amino acid capsule composition.Specifically, on the one hand, the present invention relates to a kind of vitaminAD pellets, wherein including vitamin A and calciferol；It include 2~200,000 I.U. vitamin As, 0.2~20,000 I.U. vitamin Ds in its every 1 gram of pellet2.The invention further relates to the preparation method of the vitaminAD pellet, the capsules of the compound recipe amino acid vitamin micro pill comprising the vitaminAD pellet.VitaminAD pellet of the present invention and its capsule obtained have the characteristics that better than existing product.

Description

VitaminAD pellet and compound amino acid capsule composition comprising it
Technical field
It is this that there is partial size that is small and concentrating and be particularly suitable for application as the present invention relates to a kind of vitaminAD pellet The filler or filler component of hard capsule.The invention further relates to the preparation methods of this vitaminAD pellet.In addition sheet Invention further relates to a kind of micro pill capsule and preparation method thereof, specifically, be related to it is a kind of comprising 8 kinds of amino acid and 11 kinds of vitamins The capsule of pellet, also referred to as compound amino acid capsule (8-11), further relate to the preparation method of the capsule.
Background technique
Protein is the material base of human life activity, human body items physiological function, especially immune function, cell damage The repair function and growth and development function of wound, with its be metabolized it is normal whether have extremely close relationship.Under normal circumstances, people Body is to obtain various amino acid by the protein in food to guarantee the normal of body protein metabolism.It is closed in human body protein At in required 20 kinds of amino acid, wherein having 8 kinds of amino acid is essential amino acid, this 8 kinds of amino acid are that body is interior originally Body cannot synthesize and be necessarily dependent upon external supply.They are isoleucine, leucine, lysine, phenylalanine, Soviet Union's ammonia Acid, valine, methionine and tryptophan.Protein is synthesized, this 8 kinds of amino acid are indispensable, and in content deficiency Or the synthesis of protein can be all influenced when matching unbalanced.
The generation of disease, development and recovery from illness during, due to various pathology and stress reaction, it is in addition improper diet or Digestive tract function is affected, and usually will appear the disorder of protein metabolism, 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, the supply for nitrogen matter in lysis.50 Age, Japan realize large scale fermentation and the purifying preparation of amino acid, provide advantageous skill for crystal type amino acid transfusion Art guarantees.Into the 1970s and 1980s, amino acid transfusion is constantly the treatment of clinically all kinds of acute diseases, seriously disease, especially pair Urgent patient and the treatment for being unable to oral consumption patient provide strong support.
But the treatment for chronic disease, especially can oral consumption patient treatment, the limitation right and wrong of amino acid transfusion It is often apparent.From vivo acid be metabolized the characteristics of in terms of, amino acid transfusion may cause vivo acid proportion it is not normal, be infused Serum amino acid concentration decline rapidly, aggravates liver denitrogen and bear, simultaneously after serum amino acid excessive concentration in journey, infusion stop It is possible that causing the adverse reactions such as infusion reaction, vein blood vessel inflammation.More importantly amino acid transfusion is only in short In play the role of promote positive nitrogen equilibrium, be used for a long time therapeutic effect it is unobvious.
Just because of this, while parenteral nutrition develops, development abroad is simultaneously perfect by crystalline amino acid, hydrolysis egg A variety of enteral nutrition preparations of the nitrogen sources such as white, complete protein composition.Enteral nutrition preparation is mainly orally ingested, and it is required to provide Nutrient meet the needs of body metabolism, enteral nutrition is conducive to keep the complete of enteron aisle structure and function compared with parenteral nutrition Whole property prevents intestinal mucosa atrophy and bacterial translocation caused by long-term parenteral, is conducive to the immunity for improving body.
Currently, the treatment of enteral nutrition is paid much attention in clinical practice both at home and abroad, especially in the long-term treatment of chronic disease In, the ratio of enteral nutrition treatment greatly exceeds the treatment of parenteral nutrition.As long as " gastrointestinal function allows, and uses enteral as far as possible Nutrition " is the principle of clinic nutrition treatment.Therefore, people are badly in need of solving the drug for enteral nutrition treatment.Due to amino acid It is unstable, it causes Amino Acid Oral Preparation product stability poor, restricts the application of Amino Acid Oral Preparation product.Chinese patent CN1781486, denomination of invention are as follows: 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 obviously changes 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 pellets, it is believed that 7 kinds of pellets in the micro pill capsule go out when will cause because of performance difference in pellet mixing, encapsulating capsule The now obvious uneven phenomenon of individual pellet contents.In addition, vitaminAD microballon used in CN101773512A can directly from RIKEN CORPORATION buys, or can be from China and buy Riken Vitamin Co., Ltd.'s import to Chinese Riken Dry AD-B 100/10P.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 are had significantly The tendency that content reduces overcomes this defect to be 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.
Summary of the invention
Goal of the invention of the invention is to provide a kind of vitaminAD pellet.Another goal of the invention of the invention is to provide The preparation method of this vitaminAD pellet.Goal of the invention of the invention is to provide a kind of containing 8 kinds of amino acid and 11 kinds of dimensions The capsule of the pellet of raw element.Another goal of the invention of the invention is to provide the preparation method of this capsule.It is unexpected Discovery it is contained into 8 kinds of amino acid and 11 kinds with of the present invention using vitaminAD pellet made from the method for the present invention After the pellet mixing of vitamin, there is this mix preparation excellent chemical stability especially to show as vitamin A and Wei Sheng The chemical stability of plain D2.It is accomplished the present invention is based on upper discovery.
Specifically, first aspect present invention provides a kind of vitaminAD pellet, wherein including vitamin A and vitamin D2。
The vitaminAD pellet of any embodiment according to a first aspect of the present invention includes 2~200,000 in every 1 gram of pellet I.U. in vitamin A, such as its every 1 gram of pellet comprising in 5~150,000 I.U. vitamin As, such as its every 1 gram of pellet comprising 8~ It include 100,000 I.U. vitamin As in 120000 I.U. vitamin As, such as its every 1 gram of pellet.
The vitaminAD pellet 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 pellet.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention includes 0.2~2 in every 1 gram of pellet Ten thousand I.U. vitamin Ds2It include 0.5~1.5 ten thousand I.U. in (it is also referred to as calciferol, ostelin etc.), such as its every 1 gram of pellet Vitamin D2, such as include 0.8~1.2 ten thousand I.U. vitamin Ds in its every 1 gram of pellet2, such as include 10,000 in its every 1 gram of pellet I.U. vitamin D2。
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, wherein also for example containing edible vegetable oil Corn oil, soybean oil, peanut oil, sunflower oil etc..
The vitaminAD pellet of any embodiment according to a first aspect of the present invention is planted comprising edible in every 1 gram of pellet Object 100~200mg of oil, such as 120~160mg, such as 130~150mg.
The vitaminAD pellet 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 pellet of any embodiment according to a first aspect of the present invention includes dehydration mountain in every 1 gram of pellet Pears 2~20mg of alcohol fatty acid ester, such as 2~15mg, such as 2~12mg.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, wherein also containing gelatin.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention includes gelatin 400 in every 1 gram of pellet ~700mg, such as 500~650mg, such as 550~600mg.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, wherein also containing sucrose.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention includes sucrose 100 in every 1 gram of pellet ~300mg, such as 150~250mg, such as 180~240mg.
The vitaminAD pellet 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, mud moor golden propyl ester and combinations thereof.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, in every 1 gram of pellet comprising anti-corrosion 1~ 5mg, such as 1.5~3mg, such as 2~3mg.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, wherein containing sodium benzoate, every 1 gram micro- It include 0.2~2mg of sodium benzoate, such as 0.5~1.5mg, such as 0.75~1mg in ball.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, wherein contain dehydroactic acid sodium, every 1 gram It include 0.5~5mg of dehydroactic acid sodium, such as 1~3mg, such as 1.2~2mg in pellet.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention is according to the method included the following steps It is prepared:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing are made to dissolve, obtains oil Property liquid；Separately gelatin and sucrose are dissolved in the water, add preservative, is stirred to dissolve, aqueous solution is obtained；
(2) oiliness liquid obtained by step (1) is added in the aqueous solution of stirring, is stirred, obtains lotion；
(3) lotion obtained by step (2) is added dropwise in the solidified oil of stirring, it is cooling, make the cream being dispersed in the solidified oil Drop solidification then filters out piller to form piller,
(4) gained piller organic solvent washing is removed to the solidified oil on surface, it is dry to get vitaminAD pellet.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, wherein in step (1), the 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 dissolution of whole materials cannot achieve when this temperature is lower than 30 DEG C.
The vitaminAD pellet 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, a small amount of water of comparison, which can be used, can be realized whole preparation process, 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 in such as below embodiment 1-5, when This temperature cannot achieve effective dissolutions of whole materials when being lower than 40 DEG C, or the water needed increase especially significantly it is for example aobvious Work increases to 9 times of gelatin amount or more.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, the wherein medium oil liquid of step (2) and water Property liquid mixing temperature be 50~100 DEG C, such as 60~80 DEG C.It has been found that in such as below embodiment 1-5, it is warm herein The lotion of uniform particle sizes can be effectively formed in degree range.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, wherein solidified oil described in step (3) Selected from vegetable oil, dimeticone, atoleine or combinations thereof.The vegetable oil such as edible vegetable oil such as corn oil, soybean Oil, peanut oil, sunflower oil etc..For example, solidification used in the step of when Examples below 1-5 prepares vitaminAD pellet (3) Oil is not soybean oil, corn oil, peanut oil, dimeticone, atoleine.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, wherein stirring described in step (3) The temperature of solidified oil is 35~100 DEG C, such as 35~70 DEG C.It has been found that in such as below embodiment 1-5, in this temperature Can pellet uniformly be solidified in range, and will cause solidified oil when temperature is lower than 30 DEG C and wash difficulty from pellet.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention is wherein cooled to 40 DEG C in step (3) Temperature below, such as 35 DEG C of temperature below are cooled to, such as be cooled to 30 DEG C of temperature below.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, it is wherein organic molten described in step (4) Agent is selected from ethyl alcohol, petroleum ether, isopropanol etc..
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, wherein drying described in step (4) are So that the moisture content in the pellet in terms of loss on drying less than 10%, be, for example, less than 7%.The loss on drying is 105 It DEG C measures within dry 2 hours and to obtain.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, average grain diameter is at 200~1200 μm In range, especially its average grain diameter is in 300~900 μ ms.It has been found that passing through in such as below embodiment 1-5 The intensity adjustment of emulsification procedure can obtain desired average grain diameter in step (2), such as can obtain when emulsion strength is high The smaller pellet of average grain diameter, and the average grain diameter of gained pellet is bigger when emulsion strength is relatively low.
The vitaminAD pellet of any embodiment according to a first aspect of the present invention, wherein the model in average grain diameter ± 50 μm 60% or more of the total pellet number of pellet number Zhan in enclosing, for example, the total pellet number of Zhan 70% or more, such as the total pellet number of Zhan 80% or more.This performance shows that pellet of the present invention has very narrow particle size distribution.It has been had now surprisingly been found that, example In such as below embodiment 1-5, when adding suitable sucrose into pellet, the narrow particle size distribution of above-mentioned presentation can be obtained Pellet；But when not adding sucrose (such as not adding sucrose in Examples below 1-5) or change plus other water solubilitys it is good The total pellet number of pellet number Zhan when good carbohydrate in the range of average grain diameter ± 50 μm is below 38%, show to be not added sucrose or The pellet of narrow particle size distribution cannot be obtained by using other carbohydrates instead.
Further, second aspect of the present invention, which provides, prepares any reality of vitaminAD pellet such as first aspect present invention The method for applying vitaminAD pellet described in scheme comprising following steps:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing are made to dissolve, obtains oil Property liquid；Separately gelatin and sucrose are dissolved in the water, add preservative, is stirred to dissolve, aqueous solution is obtained；
(2) oiliness liquid obtained by step (1) is added in the aqueous solution of stirring, is stirred, obtains lotion；
(3) lotion obtained by step (2) is added dropwise in the solidified oil of stirring, it is cooling, make the cream being dispersed in the solidified oil Drop solidification then filters out piller to form piller,
(4) gained piller organic solvent washing is removed to the solidified oil on surface, it is dry to get vitaminAD pellet.
The method of any embodiment according to a second aspect of the present invention includes 2~20 in every 1 gram of the vitaminAD pellet Comprising including 8 in 5~150,000 I.U. vitamin As, such as its every 1 gram of pellet in ten thousand I.U. vitamin As, such as its every 1 gram of pellet It include 100,000 I.U. vitamin As in~12 ten thousand I.U. vitamin As, such as its every 1 gram of pellet.
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 palmitate or vitamine A acetate or vitamin A is added to the vitaminAD pellet In.
The method of any embodiment according to a second aspect of the present invention, in every 1 gram of the vitaminAD pellet comprising 0.2~ 20000 I.U. vitamin Ds2It include 0.5~1.5 ten thousand in (it is also referred to as calciferol, ostelin etc.), such as its every 1 gram of pellet I.U. vitamin D2, such as include 0.8~1.2 ten thousand I.U. vitamin Ds in its every 1 gram of pellet2, such as in its every 1 gram of pellet include 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 according to a second aspect of the present invention, comprising edible in every 1 gram of the vitaminAD pellet 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, such as span20、span40、span60、span65、span80、span85。
The method of any embodiment according to a second aspect of the present invention includes dehydration in every 1 gram of the vitaminAD pellet 2~20mg of Span, such as 2~15mg, such as 2~12mg.
The method of any embodiment according to a second aspect of the present invention includes gelatin in every 1 gram of the vitaminAD pellet 400~700mg, such as 500~650mg, such as 550~600mg.
The method of any embodiment according to a second aspect of the present invention includes sucrose in every 1 gram of the vitaminAD pellet 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 are selected from sodium benzoate, dehydroactic acid Sodium, sorbic acid, potassium sorbate, mud parker methyl ester, mud moor gold ethyl ester, mud moor golden propyl ester and combinations thereof.
The method of any embodiment according to a second aspect of the present invention includes anti-corrosion in every 1 gram of the vitaminAD pellet 1~5mg of agent, such as 1.5~3mg, such as 2~3mg.
The method of any embodiment according to a second aspect of the present invention includes benzene first in every 1 gram of the vitaminAD pellet Sour 0.2~2mg of sodium, such as 0.5~1.5mg, such as 0.75~1mg.
The method of any embodiment according to a second aspect of the present invention includes dehydrogenation in every 1 gram of the vitaminAD pellet 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), the 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 lower than 30 DEG C It cannot achieve effective dissolution of whole materials.
The method of any embodiment according to a second aspect of the present invention, wherein in step (1), the 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, it can To use the water of fewer amount to can be realized whole preparation process, such as the amount of water is 2~6 times of gelatin amount, e.g. bright 3~6 times of glue amount.It has been found that cannot achieve effective dissolution of whole materials when this temperature is lower than 40 DEG C, or need Water increases especially significantly is for example increased significantly to 9 times of gelatin amount or more.
The method of any embodiment according to a second aspect of the present invention, wherein step (2) medium oil liquid is mixed 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 Lotion.
The method of any embodiment according to a second aspect of the present invention, wherein solidified oil described in step (3) is selected from plant Oil, dimeticone, atoleine or combinations thereof.The vegetable oil such as edible vegetable oil such as corn oil, soybean oil, peanut Oil, sunflower oil etc..
The method of any embodiment according to a second aspect of the present invention, the wherein solidified oil of stirring described in step (3) Temperature is 35~100 DEG C, such as 35~70 DEG C.It has been found that pellet can be made uniformly to solidify in this temperature range, and It will cause solidified oil when temperature is lower than 30 DEG C and wash difficulty from pellet.
The method of any embodiment according to a second aspect of the present invention is wherein cooled to 40 DEG C of temperature below in step (3) Degree, such as 35 DEG C of temperature below are cooled to, such as be cooled to 30 DEG C of temperature below.
The method of any embodiment according to a second aspect of the present invention, wherein organic solvent described in step (4) is selected from second Alcohol, petroleum ether, isopropanol etc..
The method of any embodiment according to a second aspect of the present invention, wherein drying described in step (4) is so that described Moisture content in pellet, 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 measure.
The method of any embodiment according to a second aspect of the present invention, obtained by vitaminAD pellet its average grain diameter In 200~1200 μ ms, especially 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 Lesser pellet, and the average grain diameter of gained pellet is bigger when emulsion strength is relatively low.
The method of any embodiment according to a second aspect of the present invention, obtained by vitaminAD pellet, wherein flat 60% or more of the total pellet number of pellet number Zhan in the range of equal partial size ± 50 μm, for example, the total pellet number of Zhan 70% or more, example Such as 80% or more of the total pellet number of Zhan.This performance shows that pellet of the present invention has very narrow particle size distribution.Go out The discovery of people's will material can obtain the pellet of narrow particle size distribution when adding suitable sucrose into pellet；But it ought not When adding sucrose or change plus pellet number Zhan when other water-soluble good carbohydrates in the range of average grain diameter ± 50 μm is total Pellet number is below 38%, shows that sucrose is not added or uses other carbohydrates instead to obtain the pellet of narrow particle size distribution.
It has been found that vitaminAD pellet of the invention can substitute completely compound amino acid capsule composition for example comprising From the vitaminAD microballon of RIKEN CORPORATION's import used in the capsule of 8 kinds of amino acid and 11 kinds of vitamin micro pills.
For this purpose, third aspect present invention provides a kind of capsule comprising the pellet of 7 kinds of spherical shapes or almost spherical, with And the capsule shells of these pellets are wrapped up, it include 8 kinds of amino acid and 11 kinds of vitamins, and 7 kinds of pellets in 7 kinds of pellets And its weight proportion (in parts by weight) are as follows:
The capsule of any embodiment according to a third aspect of the present invention, wherein the thiamine mononitrate pellet, vitamin are micro- Ball a, it vitamin micro pill b, amino acid pellet b, can be each independently known, such as can be CN101773512A and remembered It carries.
The capsule of any embodiment according to a third aspect of the present invention, wherein the vitaminAD pellet is such as the present invention Described in first aspect any embodiment, or as obtained by second aspect of the present invention any embodiment.
The capsule of any embodiment according to a third aspect of the present invention, wherein the amino acid pellet a includes with weight Measure part meter:
The capsule of any embodiment according to a third aspect of the present invention, wherein the amino acid pellet a includes with weight Measure part meter:
The capsule of any embodiment according to a third aspect of the present invention, wherein the vitamin C micro-pill includes with weight Measure part meter:
The capsule of any embodiment according to a third aspect of the present invention, wherein the vitamin C micro-pill includes following Parts by weight meter:
The capsule of any embodiment according to a third aspect of the present invention comprising the pellet of 7 kinds of spherical shapes or almost spherical, And wrap up the capsule shells of these pellets, in 7 kinds of pellets include 8 kinds of amino acid and 11 kinds of vitamins, and it is described 7 kinds it is micro- Ball and its weight proportion (in parts by weight) are as follows:
Wherein, the thiamine mononitrate pellet includes in parts by weight:
The vitamin micro pill a includes in parts by weight:
The amino acid pellet a includes in parts by weight:
The vitamin micro pill b includes in parts by weight:
The amino acid pellet b includes in parts by weight:
The vitamin C micro-pill includes in parts by weight:
The capsule of any embodiment according to a third aspect of the present invention, wherein 7 kinds of pellets and its weight proportion (in parts by weight) are as follows:
Wherein, the thiamine mononitrate pellet includes in parts by weight:
The vitamin micro pill a includes in parts by weight:
The amino acid pellet a includes in parts by weight:
The vitamin micro pill b includes in parts by weight:
Amino acid pellet b includes in parts by weight:
The vitamin C micro-pill includes following parts by weight meter:
The capsule of any embodiment according to a third aspect of the present invention, wherein 7 kinds of pellets and its weight proportion (in parts by weight) are as follows:
Thiamine mononitrate pellet 6.88
Vitamin micro pill a 17.1
Amino acid pellet a 36.8
Vitamin micro pill b 12
Amino acid pellet b 7.56
Vitamin C micro-pill 13.4
VitaminAD pellet 6.2
Wherein, the thiamine mononitrate pellet includes following parts by weight 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
The vitamin micro pill a includes 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
The amino acid pellet a includes in parts by weight:
The vitamin micro pill b includes in parts by weight:
5- hydroxyl anthranilic acid hydrochloride 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
The amino acid pellet b includes 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
The vitamin C micro-pill includes 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, with matching 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 pellet, vitamin micro pill a, amino acid pellet a, vitamin micro pill b, amino acid pellet b, vitamin C are prepared respectively Pellet, vitaminAD pellet, then this seven kinds of pellets are mixed in proportion, it is packed into capsule；
Wherein,
The vitaminAD pellet is as described in first aspect present invention any embodiment, or such as present invention second Aspect any embodiment the method is prepared；
The preparation method of described 6 kinds round pellets each independently the following steps are included:
(1) raw material is weighed in proportion, mixed raw material；
It (2) is that wetting agent prepares softwood with water, the kneading time is 4~10 minutes；
(3) it is granulated circle ball, mesh size is 0.9 millimeter, and circle ball speed is 40~60 hertz；
(4) inlet air temperature be 45~65 DEG C fluidized drying or 50~60 DEG C under the conditions of be dried in vacuo.
Method described in any embodiment according to a fourth aspect of the present invention, wherein the thiamine mononitrate pellet, vitamin Pellet a, amino acid pellet a, vitamin micro pill b, amino acid pellet b and vitamin C micro-pill preparation method be respectively as follows:
(1) thiamine mononitrate pellet the preparation method comprises the following steps: thiamine mononitrate and pharmaceutic adjuvant are mixed in proportion, be wetting with water Agent prepares softwood, integrates the time 4~6 minutes；It is granulated and justifies ball, be granulated speed 0.3pm, 0.9 millimeter of mesh size, justifying ball speed is 50~60 hertz；Fluidized drying, 45~65 DEG C of inlet air temperature；Be sieved to obtain thiamine mononitrate white pellet；
(2) vitamin micro pill a's the preparation method comprises the following steps: by niacinamide, calcium pantothenate, vitamin B6 and auxiliary material mix, be with water Wetting agent prepares softwood, and the kneading time is 4~8 minutes；It is granulated and justifies ball, be granulated speed 0.3pm, 0.9 millimeter of mesh size, justify ball 50~60 hertz of speed；Fluidized drying, inlet air temperature are 45~65 DEG C；Be sieved to obtain vitamins white pellet；
(3) amino acid pellet a's the preparation method comprises the following steps: by l-Isoleucine, L-Leu, l-Lysine hydrochloride, L- phenylpropyl alcohol Propylhomoserin, L-threonine, Valine, l-methionine and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, when kneading Between be 15~20 minutes, be granulated circle ball, be granulated speed 0.3pm, 0.9 millimeter of mesh size, circle ball speed be 40~50 hertz, In It is dried in vacuo under the conditions of 50 DEG C~60 DEG C；Be sieved to obtain amino acid yellow pellet；
(4) vitamin micro pill b's the preparation method comprises the following steps: by 5- hydroxyl anthranilic acid hydrochloride, vitamin B2, folic acid, dimension Raw element B12 and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, the kneading time is 4~6 minutes；It is granulated circle ball, is granulated Speed is 0.2pm, and 0.9 millimeter of mesh size, circle ball speed is 40~50 hertz；Fluidized drying, inlet air temperature are 45~65 DEG C； Be sieved to obtain the orange-yellow pellet of vitamin；
(5) amino acid pellet b's the preparation method comprises the following steps: L-Trp, vitamin E and auxiliary material mix in proportion, prepares softwood, Integrating the time is 5~10 minutes；It is granulated circle ball, granulation speed is 0.2pm, and 0.9 millimeter of mesh size, circle ball speed is 40~50 Hertz；It is dried in vacuo under the conditions of 50 DEG C~60 DEG C；Be sieved to obtain amino acid red pellet；
(6) vitamin C micro-pill the preparation method comprises the following steps: vitamin C and auxiliary material are mixed in proportion, be wetting agent preparation with water Softwood, kneading time are 4~6 minutes；It is granulated circle ball, granulation speed is 0.2pm, and 0.9 millimeter of mesh size, circle ball speed is 50 ~60 hertz；Fluidized drying, inlet air temperature are 45~65 DEG C；Be sieved to obtain vitamin C brown pellet；
(7) it vitaminAD pellet: is prepared according to described in second aspect of the present invention any embodiment.
Method described in any embodiment according to a fourth aspect of the present invention, wherein the thiamine mononitrate pellet, vitamin The preparation method difference of pellet a, amino acid pellet a, vitamin micro pill b, amino acid pellet b and vitamin C micro-pill this 6 kinds of pellets Are as follows:
(1) thiamine mononitrate pellet the preparation method comprises the following steps: thiamine mononitrate and pharmaceutic adjuvant are mixed in proportion, be wetting with water Agent prepares softwood, and the kneading time is 4.5~5 minutes；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 55~60 hertz Hereby；Fluidized drying, 50~60 DEG C of inlet air temperature；Be sieved to obtain thiamine mononitrate white pellet；
(2) vitamin micro pill a's the preparation method comprises the following steps: by niacinamide, calcium pantothenate, vitamin B6 and auxiliary material mix, be with water Wetting agent prepares softwood, and the kneading time is 5~7 minutes；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 55~60 hertz Hereby；Fluidized drying, inlet air temperature are 45~65 DEG C；Be sieved to obtain vitamins white pellet；
(3) amino acid pellet a's the preparation method comprises the following steps: l-Isoleucine, L-Leu, l-Lysine hydrochloride, L- phenylpropyl alcohol ammonia Acid, L-threonine, Valine, l-methionine and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, integrate the time It is 18~20 minutes, is granulated 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；Be sieved to obtain amino acid yellow pellet；
(4) vitamin micro pill b's the preparation method comprises the following steps: by 5- hydroxyl anthranilic acid hydrochloride, vitamin B2, folic acid, dimension Raw element B12 and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, the kneading time is 5~6 minutes；It is granulated circle ball, sieve 0.9 millimeter of aperture, circle ball speed are 45~50 hertz；Fluidized drying, inlet air temperature are 50~60 DEG C；Be sieved vitamin is orange Color pellet；
(5) amino acid pellet b's the preparation method comprises the following steps: L-Trp, vitamin E and auxiliary material mix in proportion, is profit with water Humectant prepares softwood, and the kneading time is 7~9 minutes；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 45~50 hertz Hereby；It is dried in vacuo under the conditions of 50 DEG C~60 DEG C；Be sieved to obtain amino acid red pellet；
(6) vitamin C micro-pill the preparation method comprises the following steps: vitamin C and auxiliary material are mixed in proportion, be wetting agent preparation with water Softwood, kneading time are 5~6 minutes；Granulation circle ball, 0.9 millimeter of mesh size, 55~60 hertz of ball speed of circle；Fluidized drying, Inlet air temperature is 50~65 DEG C；Be sieved to obtain vitamin C brown pellet；
(7) it vitaminAD pellet: is prepared according to described in second aspect of the present invention any embodiment.
Further, it is micro- to provide vitaminAD described in first aspect present invention any embodiment for fifth aspect present invention VitaminAD pellet made from ball or second aspect of the present invention any embodiment the method is preparing amino acid glue Purposes in capsule, wherein the compound amino acid capsule includes the component of following weight ratio:
The vitamin A and calciferol are present in the vitaminAD pellet.
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 pellet refers to that piller of the diameter between 0.05mm~1.5mm, preferably diameter exist 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 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/draw ratio of kind pellet, after measured, in (0.5~1): in the range of 1, such as vitaminAD produced by the present invention is micro- Minor axis/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 pellet of the average major diameter within the scope of 0.2~1.2mm, for example, can be easy to get minor axis/ The parameters such as draw ratio, major diameter and the essentially identical pellet of commercially available vitaminAD microballon.For example, it is believed that commercially available vitaminAD is micro- Pearl minor axis/draw ratio reaches 0.94:1 after measured, and major diameter is between 0.4~0.6mm；This commercially available vitaminAD microballon (vitamin-AD Beads) can directly be bought from the market, such as can be bought from RIKEN CORPORATION or from Riken Vitamin Co., Ltd. is commercially available, such as the equipment registration card number of Riken Vitamin Co., Ltd.'s import to China has H20110103 (state food and drug administration issues, trade name Riken Dry AD-B 100/10P), every 1g In include 10000 unit of 00000 unit of retinol1 and calciferol.The vitaminAD microballon of RIKEN CORPORATION also have with The identical performance of Riken Vitamin Co., Ltd. product.
The various pellets of the present invention can be used that well known to a person skilled in the art method preparations.In the present invention, in addition to dimension Outside raw element AD pellet, the preparation of extrusion spheronization pill making craft is can be used in various other pellets.In the present invention, as in addition do not said Bright, the pellet is to prepare pellet using RE/SP series extrusion spheronization machine (production of Guangzhou Xi Rui mechanical equipment Co., Ltd).
8 kinds of amino acid of one kind of the invention and 11 kinds of vitamin micro pill capsules delay in preparation treatment Chronic Liver, kidney diaseases drug Application in solution and elimination training physical fatigue food.
In the case where chronic hepatic diseases, it can be effectively improved on the basis of not increasing patient's nitrogen matter excretion burden Cell promotes the 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 is unique, technologically advanced, validity period is 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 for improving nitrogen source amino acid composition in chronic disease therapy Gesture.Firstly, it haves no need to change the dietary structure and other treatment schemes of patient, it will be able to significantly improve the amino acid of patient With protein metabolism；Secondly, it can be on the basis for not increasing patient's nitrogen matter excretion burden in the case where chronic hepatic diseases On effectively improve cell to the bioavailability of amino acid, promote the biosynthesis of protein.The present invention and existing amino acid Product technology compares, and has the advantages that
1. proportion is reasonable, science, there is good biological effect.Its different and general amino acid preparation, 8 kinds must It needs the ratio of amino acid to combine Asian-Pacific area dietary protein structure, amino acid composition and absorption of human body many factors synthesis to examine Consider and determine, wherein the large percentage of branched-chain amino acid, lysine, methionine, while adding 11 kinds of vitamins, gives full play to amino The synergistic effect of acid and vitamin makes amino acid is balanced in human body to absorb, guarantees the bioavailability of amino acid.
2. technique is unique, advanced, using extrusion granulation, circle ball production technology, solve other Moriamin Forte preparations 8 kinds of essential amino acids and 11 kinds of vitamins are respectively prepared seven kinds of pellets according to different physicochemical properties, ensure that each ingredient by disadvantage Between will not occur in storage period chemically react and degrade, improve the stability of various active constituents 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 decline.Tryptophan has indole nucleus, meets light and changes colour, stability is poor.Tryptophan is a kind of most unstable amino acid.This In 8 kinds of essential amino acids involved in inventing, since L-Trp property is unstable, be not suitable for and other 7 kinds of amino acid Mixing, the present invention are that L-Trp and vitamin E are made to individually red pellet, effectively improve the stabilization of L-Trp Property, and yellow pellet is made in other 7 kinds of amino acid, so that the stability of products of the present invention is significantly larger than similar product. The validity period of product can be more than 3 years.
3. convenient oral.Moriamin Forte preparation is in the treatment that patients with chronic diseases needs amino acid preparation for a long time, energy Enough make up certain 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 the psychological bearing capability of patient is improved again.
Capsule obtained by 1-5 of the embodiment of the present invention keeps sample for a long time at room temperature respectively, respectively at 0,3,6,9,12, 18, it samples within 24,36 months, by the method recorded in national drug standards WS1- (X-307) -2004Z, in conjunction with traditional Chinese medicines in version in 2010 The measuring method of allusion quotation two records, is measured indices to the sample of different time；The results show that various embodiments of the present invention Capsule sample kept sample through 0 month to 36 months, disintegration time limited (by official method measure) between 10~18min, 8 kinds of amino acid Content be kept within 3 years periods in 95~107% ranges of labelled amount, the content of 11 kinds of vitamin is 3 It is kept in 94~105% ranges of labelled amount in the period in year, shows that capsule of the present invention fully meets drug Quality criteria requirements.
Specific embodiment
The present invention can be further described by the following examples, however, the scope of the present invention and unlimited In following embodiments.One of skill in the art, can be with it is understood that under 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 carries out the material and test method arrived used in test general And/or specific description.Although to realize the present invention many materials and operating method used in purpose be it is known in the art that But the present invention is still described in this detail as much as possible.Following embodiment further illustrates the present invention, rather than limits this hair It is bright.In following test, when preparing pellet of the present invention, the every batch of vitaminAD pellet is with piller total weight at least 1kg's Prepared by batch, the every batch of remaining pellet is prepared with the piller total weight at least batch of 10kg.
Embodiment 1
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules of the invention are as follows: wherein thiamine mononitrate pellet, vitamin This seven kinds of pellets of pellet a, amino acid pellet a, vitamin micro pill b, amino acid pellet b, vitamin C micro-pill and vitaminAD pellet The weight ratio of round pellet are as follows:
Thiamine mononitrate pellet 6.88
Vitamin micro pill a 17.1
Amino acid pellet a 36.8
Vitamin micro pill b 12
Amino acid pellet b 7.56
Vitamin C micro-pill 13.4
VitaminAD pellet 6.2
1, the formula of thiamine mononitrate pellet are as follows:
Thiamine mononitrate 250g
Lactose 450g
Starch 45g
Calcium carboxymethylcellulose 75g
Methylcellulose 22g
Hydroxypropyl cellulose 19g
Titanium dioxide 23g
Microcrystalline cellulose 116g
2, the formula of vitamin micro pill a are as follows:
Niacinamide 360g
Calcium pantothenate 100g
Vitamin B6 43g
Lactose 77g
Calcium carboxymethylcellulose 140g
Hydroxypropyl cellulose 18g
Microcrystalline cellulose 200g
Starch 83g
3, the formula of amino acid pellet a is
L-Isoleucine 46g
L-Leu 142g
L-Lysine hydrochloride 193g
L-phenylalanine 39g
L-threonine 33g
Valine 52g
L-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
4, the formula of vitamin micro pill b are as follows:
5- hydroxyl anthranilic acid hydrochloride 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
5, the formula of amino acid pellet b are as follows:
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
6, the formula of vitamin C micro-pill are as follows:
Vitamin C 463g
Lactose 271g
Starch 60.3g
Microcrystalline cellulose 75.6g
Calcium carboxymethylcellulose 45g
Macrogol 6000 38g
Methylcellulose 18g
Chocolate pigment 2.9g
Hydroxypropyl cellulose 26.2g
Citric acid 30g
7, the formula rate (every 1000mg) of vitaminAD pellet are as follows:
Retinol Palmitate 58.8mg (100,000 iu vitamin A)
Corn oil 141.2mg
Calciferol 0.25mg (10,000 iu calciferol)
Span20 10mg
Gelatin 572mg
Sodium benzoate 0.87mg
Dehydroactic acid sodium 1.45mg
Sucrose Add pellet total weight 1000mg made of making in right amount
Wherein, 7 kinds of microsphere and its preparations are respectively as follows:
(1) thiamine mononitrate pellet 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；It is granulated circle ball, sieve 0.9 millimeter of aperture, circle ball speed are 60 hertz；Fluidized drying, 60 DEG C of inlet air temperature, dry 3 hours；Be sieved to obtain thiamine mononitrate White pellet；
(2) vitamin micro pill a is prepared: by niacinamide, calcium pantothenate, vitamin B6, lactose, calcium carboxymethylcellulose, hydroxypropyl Base cellulose, microcrystalline cellulose and starch mixing prepare softwood, and the kneading time is 7 minutes；It is granulated circle ball, 0.9 milli of mesh size Rice, circle ball speed are 60 hertz；Fluidized drying, inlet air temperature are 65 DEG C, dry 5 hours；Be sieved vitamins white is micro- Ball；
(3) prepare amino acid pellet a: each material mixes in proportion, prepares softwood, and the kneading time is 20 minutes, is granulated circle Ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz, is dried in vacuo 15 hours under the conditions of 60 DEG C；Be sieved to obtain amino acid Huang Color pellet；
(4) prepare vitamin micro pill b: by 5- hydroxyl anthranilic acid 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；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；Fluidized drying, dry 4 hours, air inlet temperature Degree is 60 DEG C；Be sieved to obtain the orange-yellow pellet of vitamin；
(5) amino acid pellet b:L- tryptophan, vitamin E, lactose, starch, calcium carboxymethylcellulose, Methyl cellulose are prepared Element, hydroxypropyl cellulose, haematochrome, uranidin and alumina silicate mix in proportion, prepare softwood, and the kneading time is 7 minutes；It is granulated Circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；20 hours are dried in vacuo under the conditions of 60 DEG C；Be sieved to obtain amino Sour red pellet；
(6) it prepares vitamin C micro-pill: each material is mixed in proportion, prepare softwood, the kneading time is 5~6 minutes；It makes Grain circle ball, 0.9 millimeter of mesh size, 60 hertz of ball speed of circle；3 hours of fluidized drying, inlet air temperature are 65 DEG C；It is sieved to obtain and tie up Raw element C brown pellet；
(7) vitaminAD pellet:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (45 DEG C) are made to dissolve, Obtain oiliness liquid；Separately by gelatin and sucrose dissolution (75 DEG C) Yu Shui (water and gelatin weight ratio 4:1), preservative is added, is stirred Mixing makes to dissolve, and obtains aqueous solution；
(2) oiliness liquid obtained by step (1) is added in the aqueous solution of stirring, is stirred (65 DEG C), obtains lotion；
(3) lotion obtained by step (2) is added dropwise in the solidified oil (55 DEG C) of stirring, it is cooling (to being lower than 30 DEG C), make point The emulsion droplet being dispersed in the solidified oil is solidified to form piller, then filters out piller,
(4) gained piller is washed with organic solvent (isopropanol) to remove the solidified oil on surface, it is dry (to loss on drying Less than 7%) to get vitaminAD pellet.
7 kinds of pellets of preparation are mixed in proportion finally, are packed into capsule.
Embodiment 2
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules of the invention are as follows:
Wherein thiamine mononitrate pellet, vitamin micro pill a, amino acid pellet a, vitamin micro pill b, amino acid pellet b, dimension life The weight ratio of this seven kinds of pellet circle pellets of plain C pellet and vitaminAD pellet are as follows:
Thiamine mononitrate pellet 2.66
Vitamin micro pill a 16.35
Amino acid pellet a 35.0
Vitamin micro pill b 11.4
Amino acid pellet b 6.65
Vitamin C micro-pill 12.73
VitaminAD pellet 5.7
1, the formula of thiamine mononitrate pellet are as follows:
Thiamine mononitrate 76g
Lactose 225g
Starch 9g
Calcium carboxymethylcellulose 15g
Methylcellulose 4.4g
Hydroxypropyl cellulose 3.8g
Titanium dioxide 4.6g
Microcrystalline cellulose 58g
2, the formula of vitamin micro pill a are as follows:
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
3, the formula of amino acid pellet a are as follows:
L-Isoleucine 34g
L-Leu 105g
L-Lysine hydrochloride 144g
L-phenylalanine 29g
L-threonine 24.5g
Valine 39g
L-methionine 106g
Lactose 87g
Starch 4.2g
Methylcellulose 4g
Hydroxypropyl cellulose 2.4g
Microcrystalline cellulose 19.4g
Uranidin 0.32g
Calcium carboxymethylcellulose 4.88g
Lauryl sodium sulfate 5g
4, the formula of vitamin micro pill b are as follows:
5, the formula of amino acid pellet b are as follows:
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
6, ascorbic formula are as follows:
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
7, the formula rate (every 1000mg) of vitaminAD pellet are as follows:
Vitamine A acetate Equivalent 150,000 VA
Soybean oil 120mg
Calciferol 1.5 ten thousand VD2
Span40 2mg
Gelatin 400mg
Mud parker methyl ester 0.75mg
Mud moor gold ethyl ester 0.5mg
Sucrose Add pellet total weight 1000mg made of making in right amount
Wherein, 7 kinds of microsphere and its preparations are respectively as follows:
(1) it prepares thiamine mononitrate pellet: thiamine mononitrate and pharmaceutic adjuvant is mixed with softwood in proportion, the kneading time is 4.5 minute；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 550 hertz；Fluidized drying 5 hours, inlet air temperature 50~ 60℃；Be sieved to obtain thiamine mononitrate white pellet；
(2) it prepares vitamin micro pill a: niacinamide, calcium pantothenate, vitamin B6 and auxiliary material being mixed, prepare softwood, when kneading Between be 6 clocks；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 55~60 hertz；Fluidized drying 4 hours, inlet air temperature It is 60 DEG C；Be sieved to obtain vitamins white pellet；
(3) amino acid pellet a:L- isoleucine, L-Leu, l-Lysine hydrochloride, L-phenylalanine, L- Soviet Union ammonia are prepared Acid, Valine, l-methionine and auxiliary material mix in proportion, prepare softwood, and the kneading time is 18 minutes, are granulated circle ball, sieve 0.9 millimeter of screen distance, circle ball speed is 4 hertz, is dried in vacuo 20 hours under the conditions of 60 DEG C；Be sieved amino acid yellow is micro- Ball；
(4) prepare vitamin micro pill b: by 5- hydroxyl anthranilic acid hydrochloride, vitamin B2, folic acid, vitamin B12 and Auxiliary material mixes in proportion, prepares softwood, and the kneading time is 6 minutes；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 45 Hertz；Fluidized drying 3 hours, inlet air temperature was 50 DEG C；Be sieved to obtain the orange-yellow pellet of vitamin；
(5) amino acid pellet b:L- tryptophan, vitamin E and auxiliary material are prepared to mix in proportion, prepares softwood, integrates the time It is 8 minutes；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；It is dried in vacuo 20 hours under the conditions of 60 DEG C； Be sieved to obtain amino acid red pellet；
(6) it prepares vitamin C micro-pill: vitamin C and auxiliary material is mixed in proportion, prepare softwood, the kneading time is 5 points Clock；Granulation circle ball, 0.9 millimeter of mesh size, 60 hertz of ball speed of circle；Fluidized drying 5 hours, inlet air temperature was 60 DEG C；Sieving Obtain vitamin C brown pellet；
(7) vitaminAD pellet:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (35 DEG C) are made to dissolve, Obtain oiliness liquid；Separately by gelatin and sucrose dissolution (100 DEG C) Yu Shui (water and gelatin weight ratio 2:1), preservative is added, is stirred Mixing makes to dissolve, and obtains aqueous solution；
(2) oiliness liquid obtained by step (1) is added in the aqueous solution of stirring, is stirred (100 DEG C), obtains lotion；
(3) lotion obtained by step (2) is added dropwise in the solidified oil (50 DEG C) of stirring, it is cooling (to being lower than 25 DEG C), make point The emulsion droplet being dispersed in the solidified oil is solidified to form piller, then filters out piller,
(4) gained piller is washed with organic solvent (ethyl alcohol) to remove the solidified oil on surface, drying is (small to loss on drying In 7%) to get vitaminAD pellet.
7 kinds of pellets of preparation are mixed in proportion finally, are packed into capsule.
Embodiment 3
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules are as follows:
Thiamine mononitrate pellet, vitamin micro pill a, amino acid pellet a, vitamin micro pill b, amino acid pellet b, vitamin C The weight ratio of this seven kinds of pellet circle pellets of pellet and vitaminAD pellet are as follows:
Thiamine mononitrate pellet 9.9
Vitamin micro pill a 20.5
Amino acid pellet a 44.1
Vitamin micro pill b 14.4
Amino acid pellet b 10.5
Vitamin C micro-pill 16.0
VitaminAD pellet 9.36
1, the formula of thiamine mononitrate pellet are as follows:
2, the formula of vitamin micro pill a are as follows:
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
3, the formula of amino acid pellet a are as follows:
L-Isoleucine 80g
L-Leu 248g
L-Lysine hydrochloride 338g
L-phenylalanine 67g
L-threonine 56g
Valine 90g
L-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
4, the formula that vitamin micro pill b includes are as follows:
5- hydroxyl anthranilic acid hydrochloride 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
5, amino acid pellet b includes 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
6, the formula of vitamin C micro-pill are as follows:
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
7, the formula rate (every 1000mg) of vitaminAD pellet are as follows:
Vitamin A Equivalent 50,000 VA
Peanut oil 160mg
Calciferol 0.5 ten thousand VD2
Span60 20mg
Gelatin 700mg
Sorbic acid 0.65mg
Potassium sorbate 1mg
Sucrose Add pellet total weight 1000mg made of making in right amount
Wherein, 7 kinds of microsphere and its preparations are respectively as follows:
(1) it prepares thiamine mononitrate pellet: thiamine mononitrate and pharmaceutic adjuvant being mixed with softwood in proportion, integrate the time 6 Minute；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 60 hertz；Fluidized drying 4 hours, 65 DEG C of inlet air temperature；It crosses Sieve to obtain thiamine mononitrate white pellet；
(2) it prepares vitamin micro pill a: niacinamide, calcium pantothenate, vitamin B6 and auxiliary material being mixed, prepare softwood, when kneading Between be 8 minutes；Granulation circle ball, 0.9 millimeter of mesh size, 560 hertz of ball speed of circle；Fluidized drying 3 hours, inlet air temperature 65 ℃；Be sieved to obtain vitamins white pellet；
(3) it prepares amino acid pellet a: l-Isoleucine, L-Leu, l-Lysine hydrochloride, L-phenylalanine, L- is revived Propylhomoserin, Valine, l-methionine and auxiliary material mix in proportion, prepare softwood, and the kneading time is 20 minutes, are granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz, is dried in vacuo 15 hours under the conditions of 60 DEG C；It is sieved to obtain amino acid yellow Pellet；
(4) prepare vitamin micro pill b: by 5- hydroxyl anthranilic acid hydrochloride, vitamin B2, folic acid, vitamin B12 and Auxiliary material mixes in proportion, prepares softwood, and the kneading time is 6 minutes；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 Hertz；Fluidized drying 5 hours, inlet air temperature was 65 DEG C；Be sieved to obtain the orange-yellow pellet of vitamin；
(5) amino acid pellet b:L- tryptophan, vitamin E and auxiliary material are prepared to mix in proportion, prepares softwood, integrates the time It is 10 minutes；It is granulated 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；Be sieved to obtain amino acid red pellet；
(6) it prepares vitamin C micro-pill: vitamin C and auxiliary material is mixed in proportion, prepare softwood, the kneading time is 6 points Clock；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 60 hertz；Fluidized drying 4 hours, inlet air temperature was 65 DEG C；It crosses Sieve to obtain vitamin C brown pellet；
(7) vitaminAD pellet:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (100 DEG C) are made to dissolve, Obtain oiliness liquid；Separately by gelatin and sucrose dissolution (40 DEG C) Yu Shui (water and gelatin weight ratio 6:1), preservative is added, is stirred Mixing makes to dissolve, and obtains aqueous solution；
(2) oiliness liquid obtained by step (1) is added in the aqueous solution of stirring, is stirred (50 DEG C), obtains lotion；
(3) lotion obtained by step (2) is added dropwise in the solidified oil (70 DEG C) of stirring, it is cooling (to being lower than 40 DEG C), make point The emulsion droplet being dispersed in the solidified oil is solidified to form piller, then filters out piller,
(4) gained piller is washed with organic solvent (petroleum ether) to remove the solidified oil on surface, it is dry (to loss on drying Less than 7%) to get vitaminAD pellet.
7 kinds of pellets of preparation are mixed in proportion finally, are packed into capsule.
Embodiment 4
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules are as follows:
Thiamine mononitrate pellet, vitamin micro pill a, amino acid pellet a, vitamin micro pill b, amino acid pellet b, vitamin C The weight ratio of this seven kinds of pellet circle pellets of pellet and vitaminAD pellet are as follows:
Thiamine mononitrate pellet 47.7
Vitamin micro pill a 167.2
Amino acid pellet a 358.8
Vitamin micro pill b 117
Amino acid pellet b 70.05
Vitamin C micro-pill 130.65
VitaminAD pellet 60.9
1, the formula of thiamine mononitrate pellet are as follows: (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
2, the formula of vitamin micro pill a are as follows: (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
3, the formula of amino acid pellet a are as follows: (unit: kilogram)
4, the formula of vitamin micro pill b are as follows: (unit: kilogram)
5- hydroxyl anthranilic acid hydrochloride 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
5, the formula of amino acid pellet b are as follows: (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
6, the formula of vitamin C micro-pill are as follows: (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
7, the formula rate (every 1000mg) of vitaminAD pellet are as follows:
Wherein, 7 kinds of microsphere and its preparations are respectively as follows:
(1) it prepares thiamine mononitrate pellet: thiamine mononitrate and pharmaceutic adjuvant being mixed with softwood in proportion, integrate the time 4 Minute；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；Fluidized drying 3 hours, 65 DEG C of inlet air temperature；It crosses Sieve to obtain thiamine mononitrate white pellet；
(2) it prepares vitamin micro pill a: niacinamide, calcium pantothenate, vitamin B6 and auxiliary material being mixed, prepare softwood, when kneading Between be 4 minutes；Granulation circle ball, 0.9 millimeter of mesh size, 50 hertz of ball speed of circle；Fluidized drying 3 hours, inlet air temperature 45 ℃；Be sieved to obtain vitamins white pellet；
(3) it prepares amino acid pellet a: l-Isoleucine, L-Leu, l-Lysine hydrochloride, L-phenylalanine, L- is revived Propylhomoserin, Valine, l-methionine and auxiliary material mix in proportion, prepare softwood, and the kneading time is 15 minutes, are granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 40 hertz, is dried in vacuo 17 hours under the conditions of 50 DEG C；It is sieved to obtain amino acid yellow Pellet；
(4) prepare vitamin micro pill b: by 5- hydroxyl anthranilic acid hydrochloride, vitamin B2, folic acid, vitamin B12 and Auxiliary material mixes in proportion, prepares softwood, and the kneading time is 4 minutes；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 40 Hertz；Fluidized drying 5 hours, inlet air temperature was 45 DEG C；Be sieved to obtain the orange-yellow pellet of vitamin；
(5) amino acid pellet b:L- tryptophan, vitamin E and auxiliary material are prepared to mix in proportion, prepares softwood, integrates the time It is 5 minutes；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 40 hertz；It is dried in vacuo 18 hours under the conditions of 50 DEG C； Be sieved to obtain amino acid red pellet；
(6) it prepares vitamin C micro-pill: vitamin C and auxiliary material is mixed in proportion, prepare softwood, the kneading time is 4~6 Minute；It is granulated circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz；Fluidized drying 3 hours, inlet air temperature was 45 DEG C； Be sieved to obtain vitamin C brown pellet；
(7) vitaminAD pellet:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (80 DEG C) are made to dissolve, Obtain oiliness liquid；Separately by gelatin and sucrose dissolution (50 DEG C) Yu Shui (water and gelatin weight ratio 3:1), preservative is added, is stirred Mixing makes to dissolve, and obtains aqueous solution；
(2) oiliness liquid obtained by step (1) is added in the aqueous solution of stirring, is stirred (60 DEG C), obtains lotion；
(3) lotion obtained by step (2) is added dropwise in the solidified oil (100 DEG C) of stirring, it is cooling (to being lower than 35 DEG C), make point The emulsion droplet being dispersed in the solidified oil is solidified to form piller, then filters out piller,
(4) gained piller is washed with organic solvent (isopropanol) to remove the solidified oil on surface, it is dry (to loss on drying Less than 7%) to get vitaminAD pellet.
7 kinds of pellets of preparation are mixed in proportion finally, are packed into capsule.
Embodiment 5
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules are as follows:
Thiamine mononitrate pellet, vitamin micro pill a, amino acid pellet a, vitamin micro pill b, amino acid pellet b, vitamin C The weight ratio of this seven kinds of pellet circle pellets of pellet and vitaminAD pellet are as follows:
1, the formula of thiamine mononitrate pellet packet are as follows: (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
2, the formula of vitamin micro pill a are as follows: (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
3, the formula of amino acid pellet a are as follows: (unit: kilogram)
L-Isoleucine 6.3
L-Leu 19.5
L-Lysine hydrochloride 26.55
L-phenylalanine 5.3
L-threonine 4.45
Valine 7.1
L-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
4, the formula of vitamin micro pill b are as follows: (unit: kilogram)
5- hydroxyl anthranilic acid hydrochloride 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
5, the formula of amino acid pellet b are as follows: (unit: kilogram)
L-Trp 23.75
Vitamin E 4.9
Lactose 37.125
Starch 28.75
Calcium carboxymethylcellulose 2.73
Methylcellulose 2.985
Hydroxypropyl cellulose 1.82
Haematochrome 0.7
Uranidin 0.07
Alumina silicate 22.625
6, the formula of vitamin C micro-pill are as follows: (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
7, the formula rate (every 1000mg) of vitaminAD pellet are as follows:
Vitamine A acetate Equivalent 200,000 VA
Corn oil 200mg
Calciferol 0.2 ten thousand VD2
Span40 12mg
Gelatin 650mg
Dehydroactic acid sodium 3mg
Sucrose Add pellet total weight 1000mg made of making in right amount
Wherein, for preceding 6 kinds of microsphere and its preparations referring to embodiment 1, vitaminAD pellet preparation method is as follows:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (55 DEG C) are made to dissolve, Obtain oiliness liquid；Separately by gelatin and sucrose dissolution (85 DEG C) Yu Shui (water and gelatin weight ratio 5:1), preservative is added, is stirred Mixing makes to dissolve, and obtains aqueous solution；
(2) oiliness liquid obtained by step (1) is added in the aqueous solution of stirring, is stirred (80 DEG C), obtains lotion；
(3) lotion obtained by step (2) is added dropwise in the solidified oil (35 DEG C) of stirring, it is cooling (to being lower than 30 DEG C), make point The emulsion droplet being dispersed in the solidified oil is solidified to form piller, then filters out piller,
(4) gained piller is washed with organic solvent (ethyl alcohol) to remove the solidified oil on surface, drying is (small to loss on drying In 7%) to get vitaminAD pellet.
7 kinds of pellets of preparation are mixed in proportion finally, are packed into capsule.
Test example 1:
In the above embodiments, make wherein gained vitamin micro pill a and vitaminAD pellet according to capsule formula respectively Both of ratio mixing, then the mixture is made to set 40 DEG C of placement June, when measuring 0 month and vitamin A contains in mixture when June 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 the vitamin A or D in every a collection of aggregate sample product, with content when its June divided by content at 0 month multiplied by 100% institute Percentage is obtained, vitamin A or D are in the remaining percentage after disposition in 40 DEG C-June in as this batch of mixture；The results show that right The vitamin micro pill a made from example 1 above -5 mixes gained mixture with vitaminAD pellet, their vitamin A is residual For remaining percentage in 97.4~99.1% ranges, vitamin D remnants percentage shows this in 97.1~99.2% ranges Vitamin A and D in a little mixtures all have excellent stability；In addition, including simultaneously 8 kinds of amino to embodiment 1-5 gained Acid and 11 kinds of vitamin micro pill capsule agent carry out disposing and measure vitamin A, D remnants' percentage above-mentioned 40 DEG C-June, as a result tie up Raw element A remnants' percentage is in 97.6~99.2% ranges, and vitamin D remnants percentage is in 97.2~99.0% ranges It is interior；When this shows that vitaminAD pellet is individually mixed with vitamin micro pill a or jointly with remaining 6 kinds of pellet, wherein tieing up Essentially identical result is presented in the stability of raw element A, D.Then, using the vitaminAD microballon produced purchased from RIKEN CORPORATION (Riken Dry AD-B 100/10P contains by Riken Vitamin Co., Ltd.'s import to China, in every 1 gram of microballon Vitamin A is 10 million international units, and dimension element element D2 is 1 million international units), it is micro- with -5 gained vitamin of example 1 above respectively Ball a is according to the ratio mixing of both of capsule formula, then the mixture is made to set 40 DEG C of placements June, mixed when measuring 0 month and when 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 conjunction object In contained method measurement), for the vitamin A or D in every a collection of aggregate sample product, with content when its June divided by 0 month Shi Hanliang Multiplied by 100% gained percentage, vitamin A or D are in the remaining percentage after disposing 40 DEG C-June in as this batch of mixture Number；The results show that mixing institute with Riken Dry AD-B 100/10P for vitamin micro pill a made from example 1 above -5 Mixture is obtained, in 86.6~89.4% ranges, vitamin D remnants percentage exists their vitamin A remnants percentage In 83.6~88.7% ranges, show that vitamin A in these mixtures and D stability are undesirable；In addition, making the Riken Dry AD-B 100/10P such as replaces at the vitaminAD pellet in the embodiment 1-5 of weight respectively, and capsule is made, carries out simultaneously Dispose and measure vitamin A, D remnants' percentage 40 DEG C-June, as a result vitamin A remnants percentage is in 87.1~88.9% models In enclosing, vitamin D remnants percentage is in 84.6~89.3% ranges；This shows commercially available Riken Dry AD-B 100/ When 10P is individually mixed with vitamin micro pill a or jointly with remaining 6 kinds of pellet, wherein vitamin A, D stability pay no attention to Think.Followed by according to the method for disposition in above-mentioned 40 DEG C-June, five kinds of vitaminADs obtained by investigation 1-5 of the embodiment of the present invention are micro- The stability of ball and commercially available Riken Dry AD-B 100/10P measures their vitamin A remnants percentage and dimension respectively Raw element D remnants' percentage, this 6 batches of vitaminAD pellet/microballon vitamin A remnants percentages and vitamin D are residual as the result is shown Remaining percentage is in 97.9~99.4% ranges.The remaining percentage of vitamin A or vitamin D and following test in this test In " labelled amount " have different meanings, the two referring to difference from without positive connection.
Include 8 kinds of amino acid and 11 kinds of loaded national drug standards of vitamin micro pill capsule agent, standard No. WS1- (X-307) -2004Z, it includes 8 kinds of amino acid and 11 kinds of vitamin micro pill capsule agent which, which is suitable for the present invention, and is applicable in VitaminAD pellet replaces with Japan's reason and grinds the production resulting capsule of vitaminAD microballon in capsule of the present invention；In the present invention Capsule obtained by literary embodiment 1-5 shines the standard detection, it has been found that indices meet standard regulation.
Test example 2:
In the present invention, term pellet refers to that piller of the diameter between 0.05mm~1.5mm, preferably diameter exist 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 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/draw ratio of 7 kinds of portion pellet, after measured, in (0.5~1): in the range of 1, such as vitaminAD produced by the present invention Minor axis/draw ratio of pellet 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 pellet of the average major diameter within the scope of 0.2~1.2mm, such as can be easy to get short The parameters such as diameter/draw ratio, major diameter and the essentially identical pellet of commercially available vitaminAD microballon.For example, it is believed that commercially available vitamin AD microballon minor axis/draw ratio reaches 0.94:1 after measured, and major diameter is between 0.4~0.6mm.
As described above, the present invention can be readily available averagely when preparing vitaminAD pellet by adjusting technological parameter Partial size is in 200~1200 μ ms, especially pellet of its average grain diameter in 300~900 μ ms.For example, passing through step Suddenly the intensity adjustment of emulsification procedure can obtain desired average grain diameter in (2), such as can obtain when emulsion strength is high flat The smaller pellet of equal partial size, and the average grain diameter of gained pellet is bigger when emulsion strength is relatively low.With average grain diameter ± The percentage of the total pellet number of pellet number Zhan in the range of 50 μm is index, and to judge the width of pellet size distribution, display is real Apply in each processing step for preparing vitaminAD pellet in a 1-5, technological parameter therein is made to meet present invention provide that it is suitable After adjustment, this percentage is all larger than 70%, and both greater than 80% in especially most situations, this performance shows this hair Bright pellet has very narrow particle size distribution.
When example 1 above -5 prepares vitaminAD pellet, by drying (40~60 DEG C of hot air dryings of step (4) It is dry), it can make the moisture content (in terms of 105 DEG C of dry 2 hours gained loss on drying results) in the pellet be respectively less than 7%.In addition, it has been found that measuring the organic solvent of the possible remnants of gained vitaminAD pellet after this drying, as the result is shown These organic solvents can not be detected with vapor phase method, that is, be below its detection limit, shown vitaminAD pellet obtained by the present invention The basic residual organic solvent introduced without technique.

Claims (27)

1. a kind of vitaminAD pellet, every 1 gram of pellet is by 2~200,000 I.U. vitamin As, 0.2~20,000 I.U. vitamin Ds2, with And edible vegetable oil, sorbitan fatty acid ester, gelatin, sucrose, preservative composition；The vitaminAD pellet is according to including such as What the method for lower step was prepared:
(1) at a temperature of 35~100 DEG C, vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester are mixed Make to dissolve, obtains oiliness liquid；Separately at a temperature of 40~100 DEG C, gelatin and sucrose are dissolved in the water, preservative is added, is stirred Mixing makes to dissolve, and obtains aqueous solution；
(2) oiliness liquid obtained by step (1) is added in the aqueous solution of stirring, is stirred at a temperature of 50~100 DEG C, obtains cream Liquid；
(3) lotion obtained by step (2) is added dropwise in 35~100 DEG C of solidified oil of stirring, is cooled to 40 DEG C of temperature below, Make the emulsion droplet being dispersed in solidified oil solidification to form piller, then filters out piller；The solidified oil is selected from vegetable oil, diformazan Silicone oil, atoleine or combinations thereof；
(4) gained piller organic solvent washing is removed to the solidified oil on surface, it is dry to get vitaminAD pellet；It is described Organic solvent is selected from ethyl alcohol, petroleum ether, isopropanol；
Wherein,
Corn oil, soybean oil, peanut oil, sunflower oil are selected from as the vegetable oil of solidified oil in step (3)；
The preservative be selected from sodium benzoate, dehydroactic acid sodium, sorbic acid, potassium sorbate, mud parker methyl ester, mud moor gold ethyl ester, Mud moors golden propyl ester and combinations thereof.
2. vitaminAD pellet according to claim 1, in step (1), the oiliness liquid is in 35~80 DEG C of at a temperature of systems .
3. vitaminAD pellet according to claim 1, in step (1), the aqueous solution is in 50~85 DEG C of at a temperature of systems .
4. vitaminAD pellet according to claim 1, the temperature that step (2) medium oil liquid is mixed with aqueous solution is 60~80 ℃。
5. vitaminAD pellet according to claim 1, the temperature of the solidified oil of stirring described in step (3) is 35~70 DEG C.
6. vitaminAD pellet according to claim 1,35 DEG C of temperature below are cooled in step (3).
It include 5~150,000 I.U. vitamin As in every 1 gram of pellet 7. vitaminAD pellet according to claim 1.
It include 8~120,000 I.U. vitamin As in every 1 gram of pellet 8. vitaminAD pellet according to claim 1.
It include 100,000 I.U. vitamin As in every 1 gram of pellet 9. vitaminAD pellet according to claim 1.
It include 0.5~1.5 ten thousand I.U. vitamin Ds in every 1 gram of pellet 10. vitaminAD pellet according to claim 12。
It include 0.8~1.2 ten thousand I.U. vitamin Ds in every 1 gram of pellet 11. vitaminAD pellet according to claim 12。
It include 10,000 I.U. vitamin Ds in every 1 gram of pellet 12. vitaminAD pellet according to claim 12。
13. vitaminAD pellet according to claim 1, the vitamin A is with vitamin A or Retinol Palmitate Or the form of vitamine A acetate is added in the vitaminAD pellet.
14. vitaminAD pellet according to claim 1, edible vegetable oil is selected from corn oil, soybean oil, peanut oil, sunflower seeds Oil.
It include 100~200mg of edible vegetable oil in every 1 gram of pellet 15. vitaminAD pellet according to claim 1.
16. vitaminAD pellet according to claim 1, wherein sorbitan fatty acid ester be selected from Arlacel-20, Arlacel-40, Arlacel-60, Arlacel-65, Arlacel-80, Arlacel-85.
17. vitaminAD pellet according to claim 1, in every 1 gram of pellet comprising sorbitan fatty acid ester 2~ 20mg。
It include 400~700mg of gelatin in every 1 gram of pellet 18. vitaminAD pellet according to claim 1.
It include 100~300mg of sucrose in every 1 gram of pellet 19. vitaminAD pellet according to claim 1.
It include 1~5mg of preservative in every 1 gram of pellet 20. vitaminAD pellet according to claim 1.
It include 0.2~2mg of sodium benzoate in every 1 gram of pellet 21. vitaminAD pellet according to claim 1.
It include 0.5~5mg of dehydroactic acid sodium in every 1 gram of pellet 22. vitaminAD pellet according to claim 1.
23. vitaminAD pellet according to claim 1, moisture content is in terms of loss on drying less than 10%.
24. vitaminAD pellet according to claim 1, average grain diameter is in 200~1200 μ ms.
25. vitaminAD pellet according to claim 1, wherein pellet number Zhan Zongwei in the range of average grain diameter ± 50 μm 60% or more of ball number.
26. a kind of capsule comprising the pellet of 7 kinds of spherical shapes or almost spherical, and the capsule shells of these pellets are wrapped up, it is described It include 8 kinds of amino acid and 11 kinds of vitamins in 7 kinds of pellets, and 7 kinds of pellets and its weight proportion are in parts by weight are as follows:
Thiamine mononitrate pellet 2.66~9.9 Vitamin micro pill a 16.35~20.5 Amino acid pellet a 35.0~44.1 Vitamin micro pill b 11.4~14.4 Amino acid pellet b 6.65~10.5 Vitamin C micro-pill 12.73~16.0 VitaminAD pellet 5.7~9.36；
Wherein:
The vitaminAD pellet is as claim 1-25 is described in any item；
The thiamine mononitrate pellet includes in parts by weight:
Thiamine mononitrate 7.6~30 Lactose 22.5~67.5 Starch 0.9~8.1 Calcium carboxymethylcellulose 1.5~13.5 Methylcellulose 0.44~3.96 Hydroxypropyl cellulose 0.38~3.42 Titanium dioxide 0.46~4.14 Microcrystalline cellulose 5.8~17.4
The vitamin micro pill a includes in parts by weight:
Niacinamide 24.5~58 Calcium pantothenate 6.2~14.5 Vitamin B6 3.1~7.2 Lactose 1.94~17.46 Calcium carboxymethylcellulose 5.6~16.8 Hydroxypropyl cellulose 0.36~3.24 Microcrystalline cellulose 9.35~28.05 Starch 1.66~14.94
The amino acid pellet a includes in parts by weight:
The vitamin micro pill b includes in parts by weight:
5- hydroxyl anthranilic acid hydrochloride 0.36~0.83 Vitamin B2 4.4~12.4 Folic acid 0.36~0.83 Vitamin B12 0.0018~0.004 Lactose 25.5~76.5 Microcrystalline cellulose 15.75~47.25 Macrogol 6000 0.17~1.53 Calcium carboxymethylcellulose 0.184~1.656 Starch 1.397~12.577
The amino acid pellet b includes in parts by weight:
L-Trp 15.1~28.4 Vitamin E 3.1~5.6 Lactose 14.85~44.55 Starch 11.5~34.5 Calcium carboxymethylcellulose 0.39~3.51 Methylcellulose 0.42~3.78 Hydroxypropyl cellulose 0.26~2.34 Haematochrome 0.1~0.9 Uranidin 0.01~0.09 Alumina silicate 3.82~27.15
The vitamin C micro-pill includes in parts by weight:
Vitamin C 31.5~74.5 Lactose 13.55~40.65 Starch 1.206~10.85 Microcrystalline cellulose 1.512~13.608 Calcium carboxymethylcellulose 0.9~8.1 Macrogol 6000 0.76~6.84 Methylcellulose 0.36~3.24 Chocolate pigment 0.058~0.522 Hydroxypropyl cellulose 1~5 Citric acid 1~5
。
27. any one of the claim 1-25 vitaminAD pellet is preparing the purposes in compound amino acid capsule, wherein institute State the component that compound amino acid capsule includes following weight ratio:
The vitamin A and calciferol are present in the vitaminAD pellet.
CN201710194320.9A 2017-03-28 2017-03-28 VitaminAD pellet and compound amino acid capsule composition comprising it Active CN106902100B (en)

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CN101773512A (en) * 2010-01-25 2010-07-14 深圳万和制药有限公司 8-amino acid/11-vitamin containing micro granule capsule and preparation method thereof
CN103142633A (en) * 2013-02-22 2013-06-12 深圳万和制药有限公司 Compound amino acid capsule including eight amino acids and eleven vitamins

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PT1244472E (en) * 1999-12-23 2005-09-30 Adisseo France Sas VITAMINIC COMPOSITION IN PARTICLES

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101773512A (en) * 2010-01-25 2010-07-14 深圳万和制药有限公司 8-amino acid/11-vitamin containing micro granule capsule and preparation method thereof
CN103142633A (en) * 2013-02-22 2013-06-12 深圳万和制药有限公司 Compound amino acid capsule including eight amino acids and eleven vitamins

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