CN106902100A - VitaminAD micropill and the compound amino acid capsule composition comprising it - Google Patents
VitaminAD micropill and the compound amino acid capsule composition comprising it Download PDFInfo
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- CN106902100A CN106902100A CN201710194320.9A CN201710194320A CN106902100A CN 106902100 A CN106902100 A CN 106902100A CN 201710194320 A CN201710194320 A CN 201710194320A CN 106902100 A CN106902100 A CN 106902100A
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- micropill
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- vitaminad
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
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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
- A61K31/21—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
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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
- A61K31/33—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
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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
- A61K31/33—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
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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
- A61K31/33—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
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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
- A61K31/33—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
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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
- A61K31/33—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
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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
- A61K31/33—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
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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
- A61K31/33—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
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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
- A61K31/33—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
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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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1658—Proteins, e.g. albumin, gelatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—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
Abstract
Compound amino acid capsule composition the present invention relates to vitaminAD micropill and comprising it.Specifically, on the one hand, the present invention relates to a kind of vitaminAD micropill, wherein comprising vitamin A and calciferol;2~200,000 I.U. vitamin As, 0.2~20,000 I.U. vitamin Ds are included in its every 1 gram of micropill2.Originally the preparation method for being related to the vitaminAD micropill is returned, the capsule of the compound recipe amino acid vitamin micro pill comprising the vitaminAD micropill.The characteristics of vitaminAD micropill of the present invention and its obtained capsule have better than existing product.
Description
Technical field
The present invention relates to a kind of vitaminAD micropill, it is this with it is small and concentrate particle diameter and be particularly suitable for application as
The filler or filler component of hard capsule.The invention further relates to the preparation method of this vitaminAD micropill.Other sheet
Invention further relates to a kind of micro pill capsule and preparation method thereof, is to be related to one kind comprising 8 kinds of amino acid and 11 kinds of vitamins specifically
The capsule of micropill, also referred to as compound amino acid capsule (8-11), further relate to the preparation method of the capsule.
Background technology
Protein is the material base of human life activity, and human body items physiological function, particularly immunologic function, cell are damaged
The repair function of wound and function of growing, whether normal have extremely close relationship with it is metabolized.Under normal circumstances, people
Body is to obtain various amino acid by the protein in food to ensure the normal of body protein metabolism.Closed in human body protein
Into in 20 kinds of required amino acid, wherein having 8 kinds of amino acid for essential amino acid, this 8 kinds of amino acid are bodies interior originally
Body can not synthesize and be necessarily dependent upon external supply.They are isoleucine, leucine, lysine, phenylalanine, Soviet Union's ammonia
Acid, valine, methionine and tryptophan.For protein synthesis, this 8 kinds of amino acid are indispensable, and not enough in content
Or the synthesis of protein can be all influenceed when matching unbalanced.
During generation in disease, development and recovery from illness, due to various pathology and stress reaction, it is in addition improper diet or
Digestive tract function is affected, and the disorder of protein metabolism usually occurs, and the disorder of protein metabolism is often led with disease
The duration of the death of cause, the generation of complication and disease is closely related.Therefore, in clinical practice, the supply of nitrogen matter is
Indispensable, effective treatment means.
Since World War II, the U.S. takes the lead in releasing protein hydrolysate, for the supply of nitrogen matter in lysis.50
In the age, Japan realizes the large scale fermentation of amino acid and prepared by purifying, for crystal type amino acid transfusion provides favourable skill
Art ensures.Into the 1970s and 1980s, amino acid transfusion is constantly the treatment of clinically all kinds of acute diseases, seriously disease, particularly right
Urgent patient and be unable to oral consumption patient treatment provide strong support.
But for the treatment of chronic disease, particularly can oral consumption patient treatment, the limitation right and wrong of amino acid transfusion
It is often obvious.In terms of the characteristics of being metabolized from vivo acid, amino acid transfusion may cause vivo acid match it is not normal, infused
Serum amino acid excessive concentration in journey, transfusion stop after serum amino acid concentration decline rapidly, aggravates liver denitrogen bear, while
It is possible to cause the adverse reactions such as infusion reaction, vein blood vessel inflammation.What is more important amino acid transfusion is only in short
In play the role of to promote positive nitrogen equilibrium, long-term use therapeutic effect is obvious.
Just because of this, while parenteral nutrition develops, development abroad is simultaneously perfect by crystalline amino acid, hydrolysis egg
In vain, various enteral nutrition preparations of the nitrogen source such as complete protein composition.Enteral nutrition preparation is mainly and is orally ingested, there is provided required
Nutrient meet body metabolism the need for, EA be conducive to compared with parenteral nutrition keep enteron aisle 26S Proteasome Structure and Function it is complete
Whole property, prevents intestinal mucosa atrophy and the bacterial translocation caused by long-term parenteral, is conducive to improving the immunity of body.
At present, the treatment of EA is paid much attention in domestic and international clinical practice, particularly in the long-term treatment of chronic disease
In, the ratio of enteral nutrition treatment greatly exceed the treatment of parenteral nutrition.As long as " gastrointestinal function is allowed, as far as possible using enteral
Nutrition " is the principle of clinic nutrition treatment.Therefore, people are badly in need of solving the medicine for enteral nutrition treatment.Due to amino acid
It is unstable, cause Amino Acid Oral Preparation product stability poor, govern the application of Amino Acid Oral Preparation product.Chinese patent
CN1781486, it is entitled:A kind of amino acid and vitamine capsule preparation and preparation method thereof, it is believed that the invention system
Standby product stability is bad, and at 12 months, product appearance substantially changed colour and product content is decreased obviously.In addition,
CN101773512A discloses a kind of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules and preparation method thereof, wherein in capsule shells
Including 7 kinds of micropills, it is believed that 7 kinds of micropills in the micro pill capsule because performance is different and can caused by micropill mixing, encapsulating capsule when go out
The existing substantially uneven phenomenon of indivedual micropill contents.Additionally, the vitaminAD microballon used in CN101773512A can directly from
RIKEN CORPORATION buys, or can buy Riken Vitamin Co., Ltd.'s imports to the Riken of China from China
Dry AD-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 have significantly
The tendency of content reduction, overcomes this defect so as to clinically to provide a kind of amino acid and Wei Sheng with superior quality
Cellulose product is that those skilled in the art urgently expect.
The content of the invention
Goal of the invention of the invention is to provide a kind of vitaminAD micropill.Another goal of the invention of the invention is to provide
The preparation method of this vitaminAD micropill.Goal of the invention of the invention is to provide one kind to contain 8 kinds of amino acid and 11 kinds of dimensions
The capsule of the micropill of raw element.Another goal of the invention of the invention is the preparation method for providing this capsule.It is unexpected
Discovery, using vitaminAD micropill obtained in the inventive method, by its with of the present invention containing 8 kinds of amino acid and 11 kinds
After the micropill mixing of vitamin, this mix preparation there is excellent chemical stability to be particularly show as vitamin A and Wei Sheng
The chemical stability of plain D2.The present invention is accomplished based on upper discovery.
Specifically, first aspect present invention provides a kind of vitaminAD micropill, wherein comprising vitamin A and vitamin
D2。
The vitaminAD micropill of any embodiment, includes 2~200,000 according to a first aspect of the present invention in its every 1 gram of micropill
I.U. vitamin A, such as include 5~150,000 I.U. vitamin As in its every 1 gram of micropill, such as in its every 1 gram of micropill comprising 8~
100,000 I.U. vitamin As are included in 120000 I.U. vitamin As, such as its every 1 gram of micropill.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein the vitamin A is to tie up life
The form of other esters of plain A or Retinol Palmitate or vitamine A acetate or vitamin A is added to the dimension
In raw element AD micropills.
The vitaminAD micropill of any embodiment, includes 0.2~2 according to a first aspect of the present invention in its every 1 gram of micropill
Ten thousand I.U. vitamin Ds20.5~1.5 ten thousand I.U. are included in (it is also referred to as calciferol, ostelin etc.), such as its every 1 gram of micropill
Vitamin D2, such as 0.8~1.2 ten thousand I.U. vitamin Ds are included in its every 1 gram of micropill2, such as 10,000 are included in its every 1 gram of micropill
I.U. vitamin D2。
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also containing edible vegetable oil for example
Corn oil, soybean oil, peanut oil, sunflower oil etc..
The vitaminAD micropill of any embodiment, plants in its every 1 gram of micropill comprising edible according to a first aspect of the present invention
Thing 100~200mg of oil, such as such as 120~160mg, 130~150mg.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also containing sorbitan fatty
Acid esters, such as span20 (i.e. Arlacel-20), span40 (i.e. Arlacel-40), span60 (i.e. Arlacel-60), span65 (i.e. sapn-
65), span80 (i.e. Arlacel-80), span85 (i.e. Arlacel-85).
The vitaminAD micropill of any embodiment, includes dehydration mountain according to a first aspect of the present invention in its every 1 gram of micropill
Pears 2~20mg of alcohol fatty acid ester, such as such as 2~15mg, 2~12mg.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also containing gelatin.
The vitaminAD micropill of any embodiment, includes gelatin 400 according to a first aspect of the present invention in its every 1 gram of micropill
~700mg, such as 500~650mg, such as 550~600mg.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also containing sucrose.
The vitaminAD micropill of any embodiment, includes sucrose 100 according to a first aspect of the present invention in its every 1 gram of micropill
~300mg, such as 150~250mg, such as 180~240mg.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein also containing preservative.At one
In embodiment, the preservative is selected from Sodium Benzoate, dehydroactic acid sodium, sorbic acid, potassium sorbate, mud parker methyl ester, Ni Bo
Golden ethyl ester, the golden propyl ester of mud pool and combinations thereof.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, in its every 1 gram of micropill comprising anti-corrosion 1~
5mg, such as 1.5~3mg, such as 2~3mg.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein containing Sodium Benzoate, every 1 gram micro-
0.2~2mg of Sodium Benzoate, such as such as 0.5~1.5mg, 0.75~1mg are included in ball.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein contain dehydroactic acid sodium, every 1 gram
0.5~5mg of dehydroactic acid sodium, such as such as 1~3mg, 1.2~2mg are included in micropill.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, it is the method according to comprising the following steps
Prepare:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing are made into dissolving, obtains oil
Property liquid;Separately gelatin and sucrose are dissolved in the water, preservative is added, is stirred to dissolve, obtain aqueous solution;
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing obtains emulsion;
(3) in step (2) gained emulsion being dropped into the solidified oil of stirring, cooling makes the breast being dispersed in the solidified oil
Drop solidification then leaches piller to form piller,
(4) gained piller organic solvent washing is dried with removing the solidified oil on surface, obtains final product vitaminAD micropill.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein in step (1), described oiliness
Liquid be it is obtained at a temperature of 35~100 DEG C, it is e.g. obtained at a temperature of 35~80 DEG C.It has been found that for example below
In embodiment 1-5, effective dissolving of whole materials cannot be realized when this temperature is less than 30 DEG C.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein in step (1), described is aqueous
Liquid be it is obtained at a temperature of 40~100 DEG C, it is e.g. obtained at a temperature of 50~85 DEG C.It has been found that for example below
In embodiment 1-5, under above-mentioned treatment temperature, it is possible to use relatively more a small amount of water is to be capable of achieving overall preparation technology, such as
The amount of water is 2~6 times of gelatin amount, e.g. the 3~6 of gelatin amount times.It has been found that for example below in embodiment 1-5, when
This temperature cannot realize effective dissolving of whole materials when being less than 40 DEG C, or the water for needing particularly marked degree increases for example aobvious
Work increases to more than 9 times of gelatin amount.
The vitaminAD micropill of any embodiment, wherein step (2) medium oil liquid and water according to a first aspect of the present invention
Property liquid mixing temperature be 50~100 DEG C, such as 60~80 DEG C.It has been found that for example below in embodiment 1-5, temperature herein
The emulsion of uniform particle sizes can be effectively formed in the range of degree.
The vitaminAD micropill of any embodiment, solidified oil wherein described in step (3) according to a first aspect of the present invention
Selected from vegetable oil, dimeticone, atoleine or its combination.The vegetable oil such as edible vegetable oil such as corn oil, soybean
Oil, peanut oil, sunflower oil etc..For example, solidification used in (3) the step of when Examples below 1-5 prepares vitaminAD micropill
Oil is not soybean oil, corn oil, peanut oil, dimeticone, atoleine.
The vitaminAD micropill of any embodiment, stirs wherein described in step (3) according to a first aspect of the present invention
The temperature of solidified oil is 35~100 DEG C, such as 35~70 DEG C.It has been found that for example below in embodiment 1-5, in this temperature
In the range of can cause that micropill uniformly solidifies, and when temperature be less than 30 DEG C when can cause solidified oil that difficulty is washed from micropill.
The vitaminAD micropill of any embodiment, is wherein cooled to 40 DEG C in step (3) according to a first aspect of the present invention
Following temperature, for example, be cooled to less than 35 DEG C of temperature, for example, be cooled to less than 30 DEG C of temperature.
The vitaminAD micropill of any embodiment, wherein organic molten described in step (4) according to a first aspect of the present invention
Agent is selected from ethanol, petroleum ether, isopropanol etc..
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein drying is described in step (4)
So that the moisture in the micropill in terms of loss on drying less than 10%, be, for example, less than 7%.The loss on drying is 105
DEG C drying determines what is obtained in 2 hours.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, its average grain diameter is at 200~1200 μm
In the range of, particularly its average grain diameter is in 300~900 μ ms.It has been found that for example passing through in embodiment 1-5 below
The intensity adjustment of emulsification procedure can obtain desired average grain diameter in step (2), such as can be obtained when emulsion strength is high
The smaller micropill of average grain diameter, and the average grain diameter of gained micropill is than larger when emulsion strength is relatively low.
The vitaminAD micropill of any embodiment according to a first aspect of the present invention, wherein in the model of average grain diameter ± 50 μm
Micropill number in enclosing accounts for more than the 60% of total micropill number, for example, account for more than the 70% of total micropill number, for example, account for total micropill number
More than 80%.This performance shows that micropill of the present invention has very narrow particle size distribution.It has been had now surprisingly been found that, example
Such as, when appropriate sucrose is added in micropill, the narrow particle size distribution of above-mentioned presentation can be obtained in embodiment 1-5 below
Micropill;But when without sucrose (such as without sucrose in Examples below 1-5) or change plus other water solubilitys it is good
Micropill number during good carbohydrate in the range of average grain diameter ± 50 μm accounts for total micropill number and is below 38%, show to be not added with sucrose or
Using other carbohydrates instead can not obtain the micropill of narrow particle size distribution.
Further, second aspect present invention is provided and prepares the vitaminAD micropill any reality of such as first aspect present invention
The method for applying vitaminAD micropill described in scheme, it comprises the following steps:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing are made into dissolving, obtains oil
Property liquid;Separately gelatin and sucrose are dissolved in the water, preservative is added, is stirred to dissolve, obtain aqueous solution;
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing obtains emulsion;
(3) in step (2) gained emulsion being dropped into the solidified oil of stirring, cooling makes the breast being dispersed in the solidified oil
Drop solidification then leaches piller to form piller,
(4) gained piller organic solvent washing is dried with removing the solidified oil on surface, obtains final product vitaminAD micropill.
The method of any embodiment, includes 2~20 according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill
5~150,000 I.U. vitamin As are included in ten thousand I.U. vitamin As, such as its every 1 gram of micropill, such as 8 are included in its every 1 gram of micropill
100,000 I.U. vitamin As are included in~12 ten thousand I.U. vitamin As, such as its every 1 gram of micropill.
The method of any embodiment according to a second aspect of the present invention, wherein the vitamin A is with vitamin A or dimension
The form of other esters of raw element A palmitates or vitamine A acetate or vitamin A is added to the vitaminAD micropill
In.
The method of any embodiment according to a second aspect of the present invention, in every 1 gram of the vitaminAD micropill comprising 0.2~
20000 I.U. vitamin Ds20.5~1.5 ten thousand are included in (it is also referred to as calciferol, ostelin etc.), such as its every 1 gram of micropill
I.U. vitamin D2, such as 0.8~1.2 ten thousand I.U. vitamin Ds are included in its every 1 gram of micropill2, such as included in its every 1 gram of micropill
10000 I.U. vitamin Ds2。
The method of any embodiment according to a second aspect of the present invention, the edible vegetable oil for example corn oil, soybean oil,
Peanut oil, sunflower oil etc..
The method of any embodiment, includes edible in every 1 gram of the vitaminAD micropill according to a second aspect of the present invention
100~200mg of vegetable oil, such as 120~160mg, such as 130~150mg.
The method of any embodiment according to a second aspect of the present invention, the sorbitan fatty acid ester, for example
span20、span40、span60、span65、span80、span85。
The method of any embodiment, includes dehydration according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill
2~20mg of Span, such as 2~15mg, such as 2~12mg.
The method of any embodiment, includes gelatin according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill
400~700mg, such as 500~650mg, such as 550~600mg.
The method of any embodiment, includes sucrose according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill
100~300mg, such as 150~250mg, such as 180~240mg.
The method of any embodiment according to a second aspect of the present invention, the preservative is selected from Sodium Benzoate, dehydroactic acid
Sodium, sorbic acid, potassium sorbate, mud parker methyl ester, mud moor gold ethyl ester, the golden propyl ester of mud pool and combinations thereof.
The method of any embodiment, includes anti-corrosion according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill
1~5mg of agent, such as 1.5~3mg, such as 2~3mg.
The method of any embodiment, includes benzene first according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill
Sour 0.2~2mg of sodium, such as such as 0.5~1.5mg, 0.75~1mg.
The method of any embodiment, includes dehydrogenation according to a second aspect of the present invention in every 1 gram of the vitaminAD micropill
0.5~5mg of sodium acetate, such as 1~3mg, such as 1.2~2mg.
The method of any embodiment according to a second aspect of the present invention, wherein in step (1), described oiliness liquid is 35
It is obtained at a temperature of~100 DEG C, it is e.g. obtained at a temperature of 35~80 DEG C.It has been found that when this temperature is less than 30 DEG C
Effective dissolving of whole materials cannot be realized.
The method of any embodiment according to a second aspect of the present invention, wherein in step (1), described aqueous solution is 40
It is obtained at a temperature of~100 DEG C, it is e.g. obtained at a temperature of 50~85 DEG C.It has been found that under above-mentioned treatment temperature, can
It is to be capable of achieving overall preparation technology with the water using fewer amount, the amount of such as water is 2~6 times of gelatin amount, e.g. bright
3~6 times of glue amount.It has been found that effective dissolving of whole materials cannot be realized when this temperature is less than 40 DEG C, or need
Water particularly marked degree increases and is for example increased significantly to more than 9 times of gelatin amount.
The method of any embodiment according to a second aspect of the present invention, wherein step (2) medium oil liquid mixes with aqueous solution
Temperature be 50~100 DEG C, such as 60~80 DEG C.It has been found that uniform particle sizes can be effectively formed in this temperature range
Emulsion.
The method of any embodiment according to a second aspect of the present invention, solidified oil is selected from plant wherein described in step (3)
Oil, dimeticone, atoleine or its combination.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 solidified oil stirred wherein described in step (3)
Temperature is 35~100 DEG C, such as 35~70 DEG C.It has been found that can cause that micropill uniformly solidifies in this temperature range, and
Can cause solidified oil that difficulty is washed from micropill when temperature is less than 30 DEG C.
The method of any embodiment, is wherein cooled to less than 40 DEG C of temperature according to a second aspect of the present invention in step (3)
Degree, for example, be cooled to less than 35 DEG C of temperature, for example, be cooled to less than 30 DEG C of temperature.
The method of any embodiment according to a second aspect of the present invention, organic solvent is selected from second wherein described in step (4)
Alcohol, petroleum ether, isopropanol etc..
The method of any embodiment, dries described in being so that wherein described in step (4) according to a second aspect of the present invention
Moisture in micropill, less than 10%, is, for example, less than 7% in terms of loss on drying.The loss on drying is small in 105 DEG C of dryings 2
When determine and obtain.
The method of any embodiment according to a second aspect of the present invention, vitaminAD micropill its average grain diameter obtained by it
In 200~1200 μ ms, particularly its average grain diameter is in 300~900 μ ms.It has been found that by step (2)
The intensity adjustment of emulsification procedure can obtain desired average grain diameter, such as average grain diameter ratio can be obtained when emulsion strength is high
Less micropill, and the average grain diameter of gained micropill is than larger when emulsion strength is relatively low.
The method of any embodiment according to a second aspect of the present invention, the vitaminAD micropill obtained by it, wherein flat
Micropill number in the range of equal particle diameter ± 50 μm accounts for more than the 60% of total micropill number, for example, account for more than the 70% of total micropill number, example
Such as account for more than the 80% of total micropill number.This performance shows that micropill of the present invention has very narrow particle size distribution.Go out
The discovery that people expects, when appropriate sucrose is added in micropill, can obtain the micropill of narrow particle size distribution;But ought not
Micropill number during addition sucrose or when changing the carbohydrate for adding other water solubilitys good in the range of average grain diameter ± 50 μm is accounted for always
Micropill number is below 38%, shows to be not added with sucrose or use other carbohydrates instead that the micropill of narrow particle size distribution can not be obtained.
It has been found that vitaminAD micropill of the invention can substitute compound amino acid capsule composition completely for example including
The vitaminAD microballon from RIKEN CORPORATION's import used in 8 kinds of amino acid and 11 kinds of capsules of vitamin micro pill.
Therefore, third aspect present invention provides a kind of capsule, it includes 7 kinds of spherical or almost spherical micropills, with
And the capsule shells of these micropills are wrapped up, 8 kinds of amino acid and 11 kinds of vitamins, and 7 kinds of micropills are included in 7 kinds of micropills
And its weight proportion (in parts by weight) is:
The capsule of any embodiment according to a third aspect of the present invention, wherein the thiamine mononitrate micropill, vitamin are micro-
Ball a, vitamin micro pill b, amino acid micropill b, can be independently of one another known, for example, can be that CN101773512A is remembered
Carry.
The capsule of any embodiment according to a third aspect of the present invention, wherein the vitaminAD micropill is such as the present invention
Described in first aspect any embodiment, or as obtained by second aspect present invention any embodiment.
The capsule of any embodiment according to a third aspect of the present invention, wherein, described amino acid micropill a is included with weight
Amount part meter:
The capsule of any embodiment according to a third aspect of the present invention, wherein, described amino acid micropill a is included with weight
Amount part meter:
The capsule of any embodiment according to a third aspect of the present invention, wherein described vitamin C micro-pill is included with weight
Amount part meter:
The capsule of any embodiment according to a third aspect of the present invention, wherein described vitamin C micro-pill is comprising following
Weight portion meter:
The capsule of any embodiment according to a third aspect of the present invention, it includes 7 kinds of spherical or almost spherical micropills,
And wrap up the capsule shells of these micropills, include 8 kinds of amino acid and 11 kinds of vitamins in 7 kinds of micropills, and it is described 7 kinds it is micro-
Ball and its weight proportion (in parts by weight) are:
Wherein, described thiamine mononitrate micropill is included in parts by weight:
Described vitamin micro pill a is included in parts by weight:
Described amino acid micropill a is included in parts by weight:
Described vitamin micro pill b is included in parts by weight:
Described amino acid micropill b is included in parts by weight:
Described vitamin C micro-pill is included in parts by weight:
The capsule of any embodiment according to a third aspect of the present invention, wherein, 7 kinds of micropills and its weight proportion
(in parts by weight) it is:
Wherein, described thiamine mononitrate micropill is included in parts by weight:
Described vitamin micro pill a is included in parts by weight:
Described amino acid micropill a is included in parts by weight:
Described vitamin micro pill b is included in parts by weight:
Amino acid micropill b is included in parts by weight:
Described vitamin C micro-pill includes following weight portion meter:
The capsule of any embodiment according to a third aspect of the present invention, wherein, 7 kinds of micropills and its weight proportion
(in parts by weight) it is:
Thiamine mononitrate micropill | 6.88 |
Vitamin micro pill a | 17.1 |
Amino acid micropill a | 36.8 |
Vitamin micro pill b | 12 |
Amino acid micropill b | 7.56 |
Vitamin C micro-pill | 13.4 |
VitaminAD micropill | 6.2 |
Wherein, described thiamine mononitrate micropill includes following weight portion meter:
Thiamine mononitrate | 25 |
Lactose | 45 |
Starch | 4.5 |
Calcium carboxymethylcellulose | 7.5 |
Methylcellulose | 2.2 |
Hydroxypropyl cellulose | 1.9 |
Titanium dioxide | 2.3 |
Microcrystalline cellulose | 11.6 |
Described vitamin micro pill a is included in parts by weight:
Niacinamide | 36 |
Calcium pantothenate | 10 |
Vitamin B6 | 4.3 |
Lactose | 7.7 |
Calcium carboxymethylcellulose | 14 |
Hydroxypropyl cellulose | 1.8 |
Microcrystalline cellulose | 20 |
Starch | 8.3 |
Described amino acid micropill a is included in parts by weight:
Described vitamin micro pill b is included in parts by weight:
5- hydroxyl anthranilic acid hydrochlorides | 0.684 |
Vitamin B2 | 9.24 |
Folic acid | 0.56 |
Vitamin B12 | 0.0028 |
Lactose | 44.17 |
Microcrystalline cellulose | 31.1 |
Macrogol 6000 | 0.57 |
Calcium carboxymethylcellulose | 0.62 |
Starch | 4.68 |
Described amino acid micropill b is included in parts by weight:
L-Trp | 21.18 |
Vitamin E | 4.56 |
Lactose | 25.25 |
Starch | 19.55 |
Calcium carboxymethylcellulose | 1.66 |
Methylcellulose | 1.785 |
Hydroxypropyl cellulose | 1.15 |
Haematochrome | 0.425 |
Uranidin | 0.0425 |
Alumina silicate | 15.39 |
Described vitamin C micro-pill is included in parts by weight:
Vitamin C | 46.3 |
Lactose | 27.1 |
Starch | 6.03 |
Microcrystalline cellulose | 7.56 |
Calcium carboxymethylcellulose | 4.5 |
Macrogol 6000 | 3.8 |
Methylcellulose | 1.8 |
Chocolate pigment | 0.29 |
Hydroxypropyl cellulose | 2.62 |
Citric acid | 3。 |
The capsule of any embodiment according to a third aspect of the present invention, it has matching somebody with somebody described in specification any embodiment
Square ratio.
Fourth aspect present invention provides the preparation method of capsule described in third aspect present invention any embodiment:First
Thiamine mononitrate micropill, vitamin micro pill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, vitamin C are prepared respectively
Micropill, vitaminAD micropill, then this seven kinds of micropills are mixed in proportion, load capsule;
Wherein,
Described vitaminAD micropill is as described in first aspect present invention any embodiment, or such as present invention second
Aspect any embodiment methods described is prepared;
The preparation method of the circular micropill of described 6 kinds is comprised the following steps independently of one another:
(1) raw material is weighed in proportion, mixed material;
(2) it is that wetting agent prepares softwood with water, the kneading time is 4~10 minutes;
(3) circle ball is granulated, mesh size is 0.9 millimeter, and circle ball speed is 40~60 hertz;
(4) EAT be 45~65 DEG C fluidized drying or 50~60 DEG C under the conditions of be vacuum dried.
Method described in any embodiment according to a fourth aspect of the present invention, wherein the thiamine mononitrate micropill, vitamin
The preparation method of micropill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b and vitamin C micro-pill is respectively:
(1) preparation method of thiamine mononitrate micropill is:Thiamine mononitrate and pharmaceutic adjuvant are mixed in proportion, is wetting with water
Agent prepares softwood, integrates 4~6 minutes time;Granulation circle ball, granulates speed 0.3pm, 0.9 millimeter of mesh size, and circle ball speed is
50~60 hertz;Fluidized drying, 45~65 DEG C of EAT;Sieve to obtain thiamine mononitrate white micropill;
(2) preparation method of vitamin micro pill a is:Niacinamide, calcium pantothenate, vitamin B6 and auxiliary material are mixed, is with water
Wetting agent prepares softwood, and the kneading time is 4~8 minutes;Granulation circle ball, granulates speed 0.3pm, 0.9 millimeter of mesh size, circle ball
50~60 hertz of speed;Fluidized drying, EAT is 45~65 DEG C;Sieve to obtain vitamins white micropill;
(3) preparation method of amino acid micropill a is:By ILE, L-Leu, LYS, L- phenylpropyl alcohols
Propylhomoserin, L-threonine, Valine, METHIONINE and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, during kneading
Between be 15~20 minutes, granulation circle ball granulates speed 0.3pm, and 0.9 millimeter of mesh size, circle ball speed is 40~50 hertz,
It is vacuum dried under the conditions of 50 DEG C~60 DEG C;Sieve to obtain amino acid yellow micropill;
(4) preparation method of vitamin micro pill b is:By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, dimension
Raw element B12 and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, and the kneading time is 4~6 minutes;Granulation circle ball, granulation
Speed is 0.2pm, and 0.9 millimeter of mesh size, circle ball speed is 40~50 hertz;Fluidized drying, EAT is 45~65 DEG C;
Sieve to obtain the orange-yellow micropill of vitamin;
(5) preparation method of amino acid micropill b is:L-Trp, vitamin E and auxiliary material mix in proportion, prepare softwood,
The kneading time is 5~10 minutes;Granulation circle ball, granulation speed is 0.2pm, and 0.9 millimeter of mesh size, circle ball speed is 40~50
Hertz;It is vacuum dried under the conditions of 50 DEG C~60 DEG C;Sieve to obtain amino acid red micropill;
(6) preparation method of vitamin C micro-pill is:Vitamin C and auxiliary material are mixed in proportion, is prepared by wetting agent with water
Softwood, the kneading time is 4~6 minutes;Granulation circle ball, granulation speed is 0.2pm, and 0.9 millimeter of mesh size, circle ball speed is 50
~60 hertz;Fluidized drying, EAT is 45~65 DEG C;Sieve to obtain vitamin C brown micropill;
(7) vitaminAD micropill:Prepared according to described in second aspect present invention any embodiment.
Method described in any embodiment according to a fourth aspect of the present invention, wherein the thiamine mononitrate micropill, vitamin
The preparation method difference of micropill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b and vitamin C micro-pill this 6 kinds of micropills
For:
(1) preparation method of thiamine mononitrate micropill is:Thiamine mononitrate and pharmaceutic adjuvant are mixed in proportion, is wetting with water
Agent prepares softwood, and the kneading time is 4.5~5 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 55~60 hertz
Hereby;Fluidized drying, 50~60 DEG C of EAT;Sieve to obtain thiamine mononitrate white micropill;
(2) preparation method of vitamin micro pill a is:Niacinamide, calcium pantothenate, vitamin B6 and auxiliary material are mixed, is with water
Wetting agent prepares softwood, and the kneading time is 5~7 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 55~60 hertz
Hereby;Fluidized drying, EAT is 45~65 DEG C;Sieve to obtain vitamins white micropill;
(3) preparation method of amino acid micropill a is:ILE, L-Leu, LYS, L- phenylpropyl alcohol ammonia
Acid, L-threonine, Valine, METHIONINE and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, integrate the time
It is 18~20 minutes, granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 45~50 hertz, under the conditions of 50 DEG C~60 DEG C
Vacuum drying;Sieve to obtain amino acid yellow micropill;
(4) preparation method of vitamin micro pill b is:By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, dimension
Raw element B12 and auxiliary material mix in proportion, are that wetting agent prepares softwood with water, and the kneading time is 5~6 minutes;Granulation circle ball, screen cloth
0.9 millimeter of aperture, circle ball speed is 45~50 hertz;Fluidized drying, EAT is 50~60 DEG C;Sieve vitamin is orange
Color micropill;
(5) preparation method of amino acid micropill b is:L-Trp, vitamin E and auxiliary material mix in proportion, are profit with water
Humectant prepares softwood, and the kneading time is 7~9 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 45~50 hertz
Hereby;It is vacuum dried under the conditions of 50 DEG C~60 DEG C;Sieve to obtain amino acid red micropill;
(6) preparation method of vitamin C micro-pill is:Vitamin C and auxiliary material are mixed in proportion, is prepared by wetting agent with water
Softwood, the kneading time is 5~6 minutes;Granulation circle ball, 0.9 millimeter of mesh size, 55~60 hertz of circle ball speed;Fluidized drying,
EAT is 50~65 DEG C;Sieve to obtain vitamin C brown micropill;
(7) vitaminAD micropill:Prepared according to described in second aspect present invention any embodiment.
Further, fifth aspect present invention is micro- there is provided vitaminAD described in first aspect present invention any embodiment
Ball or vitaminAD micropill is preparing amino acid glue obtained in second aspect present invention any embodiment methods described
Purposes in capsule, wherein component of the compound amino acid capsule comprising following part by weight:
The vitamin A and calciferol are present in the vitaminAD micropill.
Any technical characteristic in any embodiment of the present invention can be combined in any embodiment of either side,
As long as this combination is not in contradiction.
In the present invention, term micropill refers to piller of the diameter between 0.05mm~1.5mm, and preferably diameter exists
Piller between 0.1mm~1.2mm.This bead can be spherical or almost spherical.In the present invention, term " approximate ball
Shape " refers to that the minor axis/draw ratio of piller is (0.2~1):1, preferably (0.5~1):1.In embodiments below, whole the 7 of preparation
Minor axis/the draw ratio of micropill is planted, after measured, in (0.5~1):In the range of 1, the obtained vitaminAD of such as present invention is micro-
Minor axis/the draw ratio of ball reaches after measured can be readily controlled in (0.9~1):In the range of 1, as noted above by adjustment
Technological parameter can be readily available micropill of the average major diameter in the range of 0.2~1.2mm, can for example be readily available minor axis/
The parameters such as draw ratio, the major diameter micropill essentially identical with commercially available vitaminAD microballon.For example, it is believed that commercially available vitaminAD is micro-
Pearl minor axis/draw ratio is after measured up to 0.94:1, and major diameter is between 0.4~0.6mm;This commercially available vitaminAD microballon
(vitamin-AD Beads) can directly buy from the market, for example, can be bought from RIKEN CORPORATION or from Riken
Vitamin Co., Ltd.s are commercially available, and the equipment registration card number of such as Riken Vitamin Co., Ltd.s import to China has
H20110103 (state food and drug administration issues, trade name Riken Dry AD-B 100/10P), it is per 1g
In include the unit of retinol1 00000 and the unit of calciferol 10000.The vitaminAD microballon of RIKEN CORPORATION also have with
Riken Vitamin Co., Ltd. product identical performances.
The various micropills of the present invention can be used and prepared well known to a person skilled in the art method.In the present invention, except dimension
Outside raw element AD micropills, other various micropills can be prepared using extrusion spheronization pill making craft.In the present invention, as do not said in addition
Bright, described micropill is to prepare micropill using RE/SP series extrusion spheronization machine (Guangzhou Xi Rui plant equipment Co., Ltd product).
8 kinds of amino acid of one kind of the invention and 11 kinds of vitamin micro pill capsules are preparing treatment Chronic Liver, kidney diaseases medicine, delay
Application in solution and elimination training physical fatigue food.
In the case of chronic hepatic diseases, can be effectively improved on the basis of patient's nitrogen matter excretion burden is not increased
Cell promotes 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules of the biosynthesis of protein to the bioavailability of amino acid
Technique uniqueness, advanced technology, the term of validity more than 3 years, product of the present invention be used for Chronic Liver, kidney and other disease treatments, alleviate and
Eliminate physical fatigue.
The present invention has protrusion excellent as the enteral nutrition preparation that nitrogen source amino acid is constituted is improved in chronic disease therapy
Gesture.First, it need not change the dietary structure and other treatment schemes of patient, it becomes possible to significantly improve the amino acid of patient
With protein metabolism;Secondly, in the case of chronic hepatic diseases, it can not increase the basis of patient's nitrogen matter excretion burden
On effectively improve bioavailability of the cell to amino acid, promote the biosynthesis of protein.It is of the invention with existing amino acid
Product technology compares, and has the following advantages that:
1. reasonable mixture ratio, science, with good biological effect.Its difference and general amino acid preparation, its 8 kinds must
Need the ratio of amino acid to combine Asian-Pacific area dietary protein structure, amino acid composition and absorption of human body many factors comprehensively to examine
Consider and determine, wherein the large percentage of branched-chain amino acid, lysine, methionine, while adding 11 kinds of vitamins, give full play to amino
Acid and the synergy of vitamin, make amino acid balanced absorption in human body, it is ensured that the bioavailability of amino acid.
2. technique is unique, advanced, using extruder grain, circle ball production technology, solves other Moriamin Forte preparations
8 kinds of essential amino acids and 11 kinds of vitamins are respectively prepared seven kinds of micropills, it is ensured that each composition by shortcoming according to different physicochemical properties
Between will not chemically react and degrade in storage period, improve the stability of various active components in product.
Most amino acid are more stable in the present invention, and wherein tryptophan is easier to decompose in preparation and storage, causes
Content declines.Tryptophan has indole nucleus, meets light and changes colour, and stability is poor.Tryptophan is a kind of least stable amino acid.This
In 8 kinds of involved essential amino acids of invention, because L-Trp property is unstable, be not suitable for and other 7 kinds of amino acid
Mixing, the present invention is that L-Trp and vitamin E are made into individually red micropill, is effectively improved the stabilization of L-Trp
Property, and other 7 kinds of amino acid are made yellow micropill so that the stability of product prepared by the present invention is significantly larger than like product.
The term of validity of product can be more than 3 years.
3. convenient oral.Moriamin Forte preparation in the treatment that patients with chronic diseases needs amino acid preparation for a long time, energy
Enough make up some deficiencies of amino acid transfusion.The present invention is particularly suited for the chronic of Long-term taking medicine, both alleviates patient
Financial burden, while improving the psychological bearing capability of patient again.
Embodiment of the present invention 1-5 gained capsules keep sample for a long time at ambient temperature respectively, respectively at 0,3,6,9,12,
18th, sample within 24,36 months, the method as described in national drug standards WS1- (X-307) -2004Z, with reference to traditional Chinese medicines in version in 2010
Two assay methods of record of allusion quotation, the sample to different time is measured indices;Result shows, various embodiments of the present invention
Capsule sample kept sample through 0 month to 36 months, disintegration time limited (by official method determine) between 10~18min, 8 kinds of amino acid
Content be respectively maintained in the range of the 95~107% of labelled amount within the time period of 3 years, 11 kinds of contents of vitamin are 3
Respectively it is maintained in the range of the 94~105% of labelled amount in the time period in year, shows that capsule of the present invention fully meets medicine
Quality criteria requirements.
Specific embodiment
The present invention can be conducted further description by the following examples, however, the scope of the present invention is not limited
In following embodiments.One of skill in the art, can be with it is understood that on the premise of without departing substantially from the spirit and scope of the present invention
Various change and modification are carried out to the present invention.The present invention to used in experiment to material and test method carry out generality
And/or specific description.Although for realize many materials that the object of the invention used and operating method be it is known in the art that
But the present invention is still described in detail as far as possible herein.Following examples further illustrate the present invention, rather than limiting this hair
It is bright.In following experiment, when preparing micropill of the present invention, vitaminAD micropill is per batch with piller gross weight meter at least 1kg's
Batch is prepared, and remaining micropill is prepared per batch with the piller gross weight meter at least batch of 10kg.
Embodiment 1
The formula of 8 kinds of amino acid of the invention and 11 kinds of vitamin micro pill capsules is:Wherein thiamine mononitrate micropill, vitamin
Micropill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, vitamin C micro-pill and vitaminAD micropill this seven kinds of micropills
The weight ratio of circular micropill is:
Thiamine mononitrate micropill | 6.88 |
Vitamin micro pill a | 17.1 |
Amino acid micropill a | 36.8 |
Vitamin micro pill b | 12 |
Amino acid micropill b | 7.56 |
Vitamin C micro-pill | 13.4 |
VitaminAD micropill | 6.2 |
1st, the formula of thiamine mononitrate micropill is:
Thiamine mononitrate | 250g |
Lactose | 450g |
Starch | 45g |
Calcium carboxymethylcellulose | 75g |
Methylcellulose | 22g |
Hydroxypropyl cellulose | 19g |
Titanium dioxide | 23g |
Microcrystalline cellulose | 116g |
2nd, the formula of vitamin micro pill a is:
Niacinamide | 360g |
Calcium pantothenate | 100g |
Vitamin B6 | 43g |
Lactose | 77g |
Calcium carboxymethylcellulose | 140g |
Hydroxypropyl cellulose | 18g |
Microcrystalline cellulose | 200g |
Starch | 83g |
3rd, the formula of amino acid micropill a is
ILE | 46g |
L-Leu | 142g |
LYS | 193g |
L-phenylalanine | 39g |
L-threonine | 33g |
Valine | 52g |
METHIONINE | 143g |
Lactose | 176g |
Starch | 21g |
Methylcellulose | 20g |
Hydroxypropyl cellulose | 12g |
Microcrystalline cellulose | 97g |
Uranidin | 1.6g |
Calcium carboxymethylcellulose | 24.4g |
Lauryl sodium sulfate | 15g |
4th, the formula of vitamin micro pill b is:
5- hydroxyl anthranilic acid hydrochlorides | 6.84g |
Vitamin B2 | 92.4g |
Folic acid | 5.6g |
Vitamin B12 | 0.028g |
Lactose | 441.7g |
Microcrystalline cellulose | 311g |
Macrogol 6000 | 5.7g |
Calcium carboxymethylcellulose | 6.2g |
Starch | 46.8 |
5th, the formula of amino acid micropill b is:
L-Trp | 211.8g |
Vitamin E | 45.6g |
Lactose | 252.5g |
Starch | 195.5g |
Calcium carboxymethylcellulose | 16.6g |
Methylcellulose | 17.85g |
Hydroxypropyl cellulose | 11.5g |
Haematochrome | 4.25g |
Uranidin | 0.425g |
Alumina silicate | 153.9g |
6th, the formula of vitamin C micro-pill is:
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 |
7th, the formula rate (per 1000mg) of vitaminAD micropill is:
Retinol Palmitate | 58.8mg (100,000 iu vitamin As) |
Corn oil | 141.2mg |
Calciferol | 0.25mg (10,000 iu calciferols) |
Span20 | 10mg |
Gelatin | 572mg |
Sodium Benzoate | 0.87mg |
Dehydroactic acid sodium | 1.45mg |
Sucrose | Plus make the micropill gross weight 1000mg being made in right amount |
Wherein, 7 kinds of microsphere and its preparations are respectively:
(1) thiamine mononitrate micropill is prepared:By thiamine mononitrate, lactose, starch, calcium carboxymethylcellulose, methylcellulose, hydroxyl
Propyl cellulose, titanium dioxide and microcrystalline cellulose are mixed with softwood in proportion, and the kneading time is 5 minutes;Granulation circle ball, screen cloth
0.9 millimeter of aperture, circle ball speed is 60 hertz;Fluidized drying, 60 DEG C of EAT dries 3 hours;Sieve to obtain thiamine mononitrate
White micropill;
(2) vitamin micro pill a is prepared:By niacinamide, calcium pantothenate, vitamin B6, lactose, calcium carboxymethylcellulose, hydroxypropyl
The mixing of base cellulose, microcrystalline cellulose and starch, prepares softwood, and the kneading time is 7 minutes;Granulation circle ball, the milli of mesh size 0.9
Rice, circle ball speed is 60 hertz;Fluidized drying, EAT is 65 DEG C, dries 5 hours;Sieve vitamins white is micro-
Ball;
(3) amino acid micropill a is prepared:Each material mixes in proportion, prepares softwood, and the kneading time is 20 minutes, granulation circle
Ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz, is vacuum dried 15 hours under the conditions of 60 DEG C;Sieve to obtain amino acid Huang
Color micropill;
(4) vitamin micro pill b is prepared:By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, vitamin B12 and
Lactose, microcrystalline cellulose, Macrogol 6000, calcium carboxymethylcellulose and starch mix in proportion, prepare softwood, integrate the time
It is 6 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz;Fluidized drying, dries 4 hours, enters wind-warm syndrome
Spend is 60 DEG C;Sieve to obtain the orange-yellow micropill of vitamin;
(5) amino acid micropill b is prepared:L-Trp, vitamin E, lactose, starch, calcium carboxymethylcellulose, Methyl cellulose
Element, hydroxypropyl cellulose, haematochrome, uranidin and alumina silicate mix in proportion, prepare softwood, and the kneading time is 7 minutes;Granulation
Circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz;20 hours are vacuum dried under the conditions of 60 DEG C;Sieve to obtain amino
Sour red micropill;
(6) vitamin C micro-pill is prepared:Each material is mixed in proportion, softwood is prepared, the kneading time is 5~6 minutes;Make
Grain circle ball, 0.9 millimeter of mesh size, 60 hertz of circle ball speed;3 hours of fluidized drying, EAT is 65 DEG C;Sieving to tie up
Raw element C brown micropills;
(7) vitaminAD micropill:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (45 DEG C) are made into dissolving,
Obtain oiliness liquid;It is another that by gelatin and sucrose dissolving (75 DEG C), in water, (water compares 4 with gelatin weight:1) in, preservative is added, is stirred
Mixing makes dissolving, obtains aqueous solution;
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing (65 DEG C) obtains emulsion;
(3) in step (2) gained emulsion being dropped into the solidified oil (55 DEG C) of stirring, cooling (to being less than 30 DEG C) makes point
The emulsion droplet being dispersed in the solidified oil is solidified to form piller, then leaches piller,
(4) gained piller is washed with organic solvent (isopropanol) to remove the solidified oil on surface, is dried (to loss on drying
Less than 7%), obtaining final product vitaminAD micropill.
Finally the 7 kinds of micropills for preparing are mixed in proportion, loads capsule.
Embodiment 2
The formula of 8 kinds of amino acid of the invention and 11 kinds of vitamin micro pill capsules is:
Wherein thiamine mononitrate micropill, vitamin micro pill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, dimension life
The weight ratio of plain C micropills and vitaminAD micropill this seven kinds of micropills circle micropills is:
Thiamine mononitrate micropill | 2.66 |
Vitamin micro pill a | 16.35 |
Amino acid micropill a | 35.0 |
Vitamin micro pill b | 11.4 |
Amino acid micropill b | 6.65 |
Vitamin C micro-pill | 12.73 |
VitaminAD micropill | 5.7 |
1st, the formula of thiamine mononitrate micropill is:
Thiamine mononitrate | 76g |
Lactose | 225g |
Starch | 9g |
Calcium carboxymethylcellulose | 15g |
Methylcellulose | 4.4g |
Hydroxypropyl cellulose | 3.8g |
Titanium dioxide | 4.6g |
Microcrystalline cellulose | 58g |
2nd, the formula of vitamin micro pill a is:
Niacinamide | 245g |
Calcium pantothenate | 62g |
Vitamin B6 | 31g |
Lactose | 19.4g |
Calcium carboxymethylcellulose | 56g |
Hydroxypropyl cellulose | 3.6g |
Microcrystalline cellulose | 93.5g |
Starch | 16.6g |
3rd, the formula of amino acid micropill a is:
ILE | 34g |
L-Leu | 105g |
LYS | 144g |
L-phenylalanine | 29g |
L-threonine | 24.5g |
Valine | 39g |
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 |
4th, the formula of vitamin micro pill b is:
5th, the formula of amino acid micropill b is:
L-Trp | 151g |
Vitamin E | 31g |
Lactose | 148.5g |
Starch | 115g |
Calcium carboxymethylcellulose | 3.9g |
Methylcellulose | 4.2g |
Hydroxypropyl cellulose | 2.6g |
Haematochrome | 1g |
Uranidin | 0.1g |
Alumina silicate | 38.2g |
6th, ascorbic formula is:
Vitamin C | 315g |
Lactose | 135.5g |
Starch | 12.06g |
Microcrystalline cellulose | 15.12g |
Calcium carboxymethylcellulose | 9g |
Macrogol 6000 | 7.6g |
Methylcellulose | 3.6g |
Chocolate pigment | 0.58g |
Hydroxypropyl cellulose | 10g |
Citric acid | 10g |
7th, the formula rate (per 1000mg) of vitaminAD micropill is:
Vitamine A acetate | Equivalent 150,000 VA |
Soybean oil | 120mg |
Calciferol | |
Span40 | 2mg |
Gelatin | 400mg |
Mud parker methyl ester | 0.75mg |
Mud moor gold ethyl ester | 0.5mg |
Sucrose | Plus make the micropill gross weight 1000mg being made in right amount |
Wherein, 7 kinds of microsphere and its preparations are respectively:
(1) thiamine mononitrate micropill is prepared:Thiamine mononitrate and pharmaceutic adjuvant are mixed with softwood in proportion, the kneading time is
4.5 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 550 hertz;Fluidized drying 5 hours, EAT 50~
60℃;Sieve to obtain thiamine mononitrate white micropill;
(2) vitamin micro pill a is prepared:Niacinamide, calcium pantothenate, vitamin B6 and auxiliary material are mixed, softwood is prepared, during kneading
Between be 6 clocks;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 55~60 hertz;Fluidized drying 4 hours, EAT
It is 60 DEG C;Sieve to obtain vitamins white micropill;
(3) amino acid micropill a is prepared:ILE, L-Leu, LYS, L-phenylalanine, L- Soviet Unions ammonia
Acid, Valine, METHIONINE and auxiliary material mix in proportion, prepare softwood, and the kneading time is 18 minutes, granulation circle ball, sieve
0.9 millimeter of screen distance, circle ball speed is 4 hertz, is vacuum dried 20 hours under the conditions of 60 DEG C;Sieve amino acid yellow is micro-
Ball;
(4) vitamin micro pill b is prepared:By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, vitamin B12 and
Auxiliary material mixes in proportion, prepares softwood, and the kneading time is 6 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 45
Hertz;Fluidized drying 3 hours, EAT is 50 DEG C;Sieve to obtain the orange-yellow micropill of vitamin;
(5) amino acid micropill b is prepared:L-Trp, vitamin E and auxiliary material mix in proportion, prepare softwood, integrate the time
It is 8 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz;It is vacuum dried 20 hours under the conditions of 60 DEG C;
Sieve to obtain amino acid red micropill;
(6) vitamin C micro-pill is prepared:Vitamin C and auxiliary material are mixed in proportion, softwood is prepared, the kneading time is 5 points
Clock;Granulation circle ball, 0.9 millimeter of mesh size, 60 hertz of circle ball speed;Fluidized drying 5 hours, EAT is 60 DEG C;Sieving
Obtain vitamin C brown micropill;
(7) vitaminAD micropill:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (35 DEG C) are made into dissolving,
Obtain oiliness liquid;It is another that by gelatin and sucrose dissolving (100 DEG C), in water, (water compares 2 with gelatin weight:1) in, preservative is added, is stirred
Mixing makes dissolving, obtains aqueous solution;
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing (100 DEG C) obtains emulsion;
(3) in step (2) gained emulsion being dropped into the solidified oil (50 DEG C) of stirring, cooling (to being less than 25 DEG C) makes point
The emulsion droplet being dispersed in the solidified oil is solidified to form piller, then leaches piller,
(4) gained piller is washed with organic solvent (ethanol) to remove the solidified oil on surface, drying is (small to loss on drying
In 7%), vitaminAD micropill is obtained final product.
Finally the 7 kinds of micropills for preparing are mixed in proportion, loads capsule.
Embodiment 3
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules is:
Thiamine mononitrate micropill, vitamin micro pill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, vitamin C
The weight ratio of micropill and vitaminAD micropill this seven kinds of micropills circle micropills is:
Thiamine mononitrate micropill | 9.9 |
Vitamin micro pill a | 20.5 |
Amino acid micropill a | 44.1 |
Vitamin micro pill b | 14.4 |
Amino acid micropill b | 10.5 |
Vitamin C micro-pill | 16.0 |
VitaminAD micropill | 9.36 |
1st, the formula of thiamine mononitrate micropill is:
2nd, the formula of vitamin micro pill a is:
Niacinamide | 580g |
Calcium pantothenate | 145g |
Vitamin B6 | 72g |
Lactose | 174.6g |
Calcium carboxymethylcellulose | 168g |
Hydroxypropyl cellulose | 32.4g |
Microcrystalline cellulose | 280.5g |
Starch | 149.4g |
3rd, the formula of amino acid micropill a is:
ILE | 80g |
L-Leu | 248g |
LYS | 338g |
L-phenylalanine | 67g |
L-threonine | 56g |
Valine | 90g |
METHIONINE | 245g |
Lactose | 264g |
Starch | 37.8g |
Methylcellulose | 36g |
Hydroxypropyl cellulose | 21.6g |
Microcrystalline cellulose | 174.6g |
Uranidin | 2.88g |
Calcium carboxymethylcellulose | 43.92g |
Lauryl sodium sulfate | 30g |
4th, the formula that vitamin micro pill b is included is:
5- hydroxyl anthranilic acid hydrochlorides | 8.3g |
Vitamin B2 | 124g |
Folic acid | 8.3g |
Vitamin B12 | 0.04g |
Lactose | 765g |
Microcrystalline cellulose | 472.5g |
Macrogol 6000 | 15.3g |
Calcium carboxymethylcellulose | 16.56g |
Starch | 125.77g |
5th, amino acid micropill b is included in parts by weight:
L-Trp | 284g |
Vitamin E | 56g |
Lactose | 445.5g |
Starch | 345g |
Calcium carboxymethylcellulose | 35.1g |
Methylcellulose | 37.8g |
Hydroxypropyl cellulose | 23.4g |
Haematochrome | 9g |
Uranidin | 0.9g |
Alumina silicate | 271.5g |
6th, the formula of vitamin C micro-pill is:
Vitamin C | 745g |
Lactose | 406.5g |
Starch | 108.5g |
Microcrystalline cellulose | 136.08g |
Calcium carboxymethylcellulose | 81g |
Macrogol 6000 | 68.4g |
Methylcellulose | 32.4g |
Chocolate pigment | 5.22g |
Hydroxypropyl cellulose | 50g |
Citric acid | 50g |
7th, the formula rate (per 1000mg) of vitaminAD micropill is:
Vitamin A | Equivalent 50,000 VA |
Peanut oil | 160mg |
Calciferol | |
Span60 | 20mg |
Gelatin | 700mg |
Sorbic acid | 0.65mg |
Potassium sorbate | 1mg |
Sucrose | Plus make the micropill gross weight 1000mg being made in right amount |
Wherein, 7 kinds of microsphere and its preparations are respectively:
(1) thiamine mononitrate micropill is prepared:Thiamine mononitrate and pharmaceutic adjuvant are mixed with softwood in proportion, the time 6 is integrated
Minute;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 60 hertz;Fluidized drying 4 hours, 65 DEG C of EAT;Cross
Sieve to obtain thiamine mononitrate white micropill;
(2) vitamin micro pill a is prepared:Niacinamide, calcium pantothenate, vitamin B6 and auxiliary material are mixed, softwood is prepared, during kneading
Between be 8 minutes;Granulation circle ball, 0.9 millimeter of mesh size, 560 hertz of circle ball speed;Fluidized drying 3 hours, EAT is 65
℃;Sieve to obtain vitamins white micropill;
(3) amino acid micropill a is prepared:By ILE, L-Leu, LYS, L-phenylalanine, L- Soviet Unions
Propylhomoserin, Valine, METHIONINE and auxiliary material mix in proportion, prepare softwood, and the kneading time is 20 minutes, granulation circle ball,
0.9 millimeter of mesh size, circle ball speed is 50 hertz, is vacuum dried 15 hours under the conditions of 60 DEG C;Sieve to obtain amino acid yellow
Micropill;
(4) vitamin micro pill b is prepared:By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, vitamin B12 and
Auxiliary material mixes in proportion, prepares softwood, and the kneading time is 6 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50
Hertz;Fluidized drying 5 hours, EAT is 65 DEG C;Sieve to obtain the orange-yellow micropill of vitamin;
(5) amino acid micropill b is prepared:L-Trp, vitamin E and auxiliary material mix in proportion, prepare softwood, integrate the time
It is 10 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz;Vacuum drying 15 is small under the conditions of 60 DEG C
When;Sieve to obtain amino acid red micropill;
(6) vitamin C micro-pill is prepared:Vitamin C and auxiliary material are mixed in proportion, softwood is prepared, the kneading time is 6 points
Clock;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 60 hertz;Fluidized drying 4 hours, EAT is 65 DEG C;Cross
Sieve to obtain vitamin C brown micropill;
(7) vitaminAD micropill:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (100 DEG C) are made into dissolving,
Obtain oiliness liquid;It is another that by gelatin and sucrose dissolving (40 DEG C), in water, (water compares 6 with gelatin weight:1) in, preservative is added, is stirred
Mixing makes dissolving, obtains aqueous solution;
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing (50 DEG C) obtains emulsion;
(3) in step (2) gained emulsion being dropped into the solidified oil (70 DEG C) of stirring, cooling (to being less than 40 DEG C) makes point
The emulsion droplet being dispersed in the solidified oil is solidified to form piller, then leaches piller,
(4) gained piller is washed with organic solvent (petroleum ether) to remove the solidified oil on surface, is dried (to loss on drying
Less than 7%), obtaining final product vitaminAD micropill.
Finally the 7 kinds of micropills for preparing are mixed in proportion, loads capsule.
Embodiment 4
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules is:
Thiamine mononitrate micropill, vitamin micro pill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, vitamin C
The weight ratio of micropill and vitaminAD micropill this seven kinds of micropills circle micropills is:
Thiamine mononitrate micropill | 47.7 |
Vitamin micro pill a | 167.2 |
Amino acid micropill a | 358.8 |
Vitamin micro pill b | 117 |
Amino acid micropill b | 70.05 |
Vitamin C micro-pill | 130.65 |
VitaminAD micropill | 60.9 |
1st, the formula of thiamine mononitrate micropill is:(unit:Kilogram)
Thiamine mononitrate | 16.3 |
Lactose | 33.75 |
Starch | 2.7 |
Calcium carboxymethylcellulose | 4.5 |
Methylcellulose | 1.32 |
Hydroxypropyl cellulose | 1.14 |
Titanium dioxide | 1.38 |
Microcrystalline cellulose | 8.7 |
2nd, the formula of vitamin micro pill a is:(unit:Kilogram)
Niacinamide | 30.25 |
Calcium pantothenate | 8.1 |
Vitamin B6 | 3.7 |
Lactose | 4.1 |
Calcium carboxymethylcellulose | 11.8 |
Hydroxypropyl cellulose | 0.76 |
Microcrystalline cellulose | 19.73 |
Starch | 3.5 |
3rd, the formula of amino acid micropill a is:(unit:Kilogram)
4th, the formula of vitamin micro pill b is:(unit:Kilogram)
5- hydroxyl anthranilic acid hydrochlorides | 0.465 |
Vitamin B2 | 6.05 |
Folic acid | 0.415 |
Vitamin B12 | 0.002 |
Lactose | 38.25 |
Microcrystalline cellulose | 23.625 |
Macrogol 6000 | 0.51 |
Calcium carboxymethylcellulose | 0.552 |
Starch | 4.19215 |
5th, the formula of amino acid micropill b is:(unit:Kilogram)
L-Trp | 17.1 |
Vitamin E | 3.65 |
Lactose | 22.275 |
Starch | 17.25 |
Calcium carboxymethylcellulose | 1.17 |
Methylcellulose | 1.26 |
Hydroxypropyl cellulose | 0.78 |
Haematochrome | 0.3 |
Uranidin | 0.03 |
Alumina silicate | 13.575 |
6th, the formula of vitamin C micro-pill is:(unit:Kilogram)
Vitamin C | 38.9 |
Lactose | 20.325 |
Starch | 3.618 |
Microcrystalline cellulose | 4.536 |
Calcium carboxymethylcellulose | 2.7 |
Macrogol 6000 | 2.28 |
Methylcellulose | 1.08 |
Chocolate pigment | 0.174 |
Hydroxypropyl cellulose | 1.572 |
Citric acid | 2 |
7th, the formula rate (per 1000mg) of vitaminAD micropill is:
Wherein, 7 kinds of microsphere and its preparations are respectively:
(1) thiamine mononitrate micropill is prepared:Thiamine mononitrate and pharmaceutic adjuvant are mixed with softwood in proportion, the time 4 is integrated
Minute;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz;Fluidized drying 3 hours, 65 DEG C of EAT;Cross
Sieve to obtain thiamine mononitrate white micropill;
(2) vitamin micro pill a is prepared:Niacinamide, calcium pantothenate, vitamin B6 and auxiliary material are mixed, softwood is prepared, during kneading
Between be 4 minutes;Granulation circle ball, 0.9 millimeter of mesh size, 50 hertz of circle ball speed;Fluidized drying 3 hours, EAT is 45
℃;Sieve to obtain vitamins white micropill;
(3) amino acid micropill a is prepared:By ILE, L-Leu, LYS, L-phenylalanine, L- Soviet Unions
Propylhomoserin, Valine, METHIONINE and auxiliary material mix in proportion, prepare softwood, and the kneading time is 15 minutes, granulation circle ball,
0.9 millimeter of mesh size, circle ball speed is 40 hertz, is vacuum dried 17 hours under the conditions of 50 DEG C;Sieve to obtain amino acid yellow
Micropill;
(4) vitamin micro pill b is prepared:By 5- hydroxyl anthranilic acids hydrochloride, vitamin B2, folic acid, vitamin B12 and
Auxiliary material mixes in proportion, prepares softwood, and the kneading time is 4 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 40
Hertz;Fluidized drying 5 hours, EAT is 45 DEG C;Sieve to obtain the orange-yellow micropill of vitamin;
(5) amino acid micropill b is prepared:L-Trp, vitamin E and auxiliary material mix in proportion, prepare softwood, integrate the time
It is 5 minutes;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 40 hertz;It is vacuum dried 18 hours under the conditions of 50 DEG C;
Sieve to obtain amino acid red micropill;
(6) vitamin C micro-pill is prepared:Vitamin C and auxiliary material are mixed in proportion, softwood is prepared, the kneading time is 4~6
Minute;Granulation circle ball, 0.9 millimeter of mesh size, circle ball speed is 50 hertz;Fluidized drying 3 hours, EAT is 45 DEG C;
Sieve to obtain vitamin C brown micropill;
(7) vitaminAD micropill:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (80 DEG C) are made into dissolving,
Obtain oiliness liquid;It is another that by gelatin and sucrose dissolving (50 DEG C), in water, (water compares 3 with gelatin weight:1) in, preservative is added, is stirred
Mixing makes dissolving, obtains aqueous solution;
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing (60 DEG C) obtains emulsion;
(3) in step (2) gained emulsion being dropped into the solidified oil (100 DEG C) of stirring, cooling (to being less than 35 DEG C) makes point
The emulsion droplet being dispersed in the solidified oil is solidified to form piller, then leaches piller,
(4) gained piller is washed with organic solvent (isopropanol) to remove the solidified oil on surface, is dried (to loss on drying
Less than 7%), obtaining final product vitaminAD micropill.
Finally the 7 kinds of micropills for preparing are mixed in proportion, loads capsule.
Embodiment 5
The formula of 8 kinds of amino acid and 11 kinds of vitamin micro pill capsules is:
Thiamine mononitrate micropill, vitamin micro pill a, amino acid micropill a, vitamin micro pill b, amino acid micropill b, vitamin C
The weight ratio of micropill and vitaminAD micropill this seven kinds of micropills circle micropills is:
1st, the formula of thiamine mononitrate micropill bag is:(unit:Kilogram)
Thiamine mononitrate | 27.5 |
Lactose | 56.25 |
Starch | 6.3 |
Calcium carboxymethylcellulose | 10.5 |
Methylcellulose | 3.08 |
Hydroxypropyl cellulose | 2.66 |
Titanium dioxide | 3.22 |
Microcrystalline cellulose | 14.5 |
2nd, the formula of vitamin micro pill a is:(unit:Kilogram)
Niacinamide | 47 |
Calcium pantothenate | 12.25 |
Vitamin B6 | 5.75 |
Lactose | 16.76 |
Calcium carboxymethylcellulose | 16.1 |
Hydroxypropyl cellulose | 3.0 |
Microcrystalline cellulose | 25 |
Starch | 14 |
3rd, the formula of amino acid micropill a is:(unit:Kilogram)
ILE | 6.3 |
L-Leu | 19.5 |
LYS | 26.55 |
L-phenylalanine | 5.3 |
L-threonine | 4.45 |
Valine | 7.1 |
METHIONINE | 19.4 |
Lactose | 22 |
Starch | 2.94 |
Methylcellulose | 2.8 |
Hydroxypropyl cellulose | 1.68 |
Microcrystalline cellulose | 13.58 |
Uranidin | 0.224 |
Calcium carboxymethylcellulose | 3.416 |
Lauryl sodium sulfate | 2.5 |
4th, the formula of vitamin micro pill b is:(unit:Kilogram)
5- hydroxyl anthranilic acid hydrochlorides | 0.7 |
Vitamin B2 | 10.05 |
Folic acid | 0.65 |
Vitamin B12 | 0.003 |
Lactose | 63.75 |
Microcrystalline cellulose | 39.375 |
Macrogol 6000 | 1.19 |
Calcium carboxymethylcellulose | 1.288 |
Starch | 9.78215 |
5th, the formula of amino acid micropill b is:(unit:Kilogram)
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 |
6th, the formula of vitamin C micro-pill is:(unit:Kilogram)
Vitamin C | 60.4 |
Lactose | 33.875 |
Starch | 8.44 |
Microcrystalline cellulose | 10.584 |
Calcium carboxymethylcellulose | 6.3 |
Macrogol 6000 | 5.32 |
Methylcellulose | 2.52 |
Chocolate pigment | 0.406 |
Hydroxypropyl cellulose | 3.668 |
Citric acid | 4 |
7th, the formula rate (per 1000mg) of vitaminAD micropill is:
Vitamine A acetate | Equivalent 200,000 VA |
Corn oil | 200mg |
Calciferol | |
Span40 | 12mg |
Gelatin | 650mg |
Dehydroactic acid sodium | 3mg |
Sucrose | Plus make the micropill gross weight 1000mg being made in right amount |
Wherein, preceding 6 kinds of microsphere and its preparations are referring to embodiment 1, and vitaminAD micropill preparation method is as follows:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing (55 DEG C) are made into dissolving,
Obtain oiliness liquid;It is another that by gelatin and sucrose dissolving (85 DEG C), in water, (water compares 5 with gelatin weight:1) in, preservative is added, is stirred
Mixing makes dissolving, obtains aqueous solution;
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing (80 DEG C) obtains emulsion;
(3) in step (2) gained emulsion being dropped into the solidified oil (35 DEG C) of stirring, cooling (to being less than 30 DEG C) makes point
The emulsion droplet being dispersed in the solidified oil is solidified to form piller, then leaches piller,
(4) gained piller is washed with organic solvent (ethanol) to remove the solidified oil on surface, drying is (small to loss on drying
In 7%), vitaminAD micropill is obtained final product.
Finally the 7 kinds of micropills for preparing are mixed in proportion, loads capsule.
Test example 1:
In the various embodiments described above, make wherein gained vitamin micro pill a with vitaminAD micropill according to capsule formula respectively
In the mixing of the two ratio, then the mixture is put 40 DEG C of placement June, vitamin A contains when determining 0 month and during June in mixture
Amount and vitamin D content (are surveyed according to method contained in Chinese Pharmacopoeia two vitaminAD soft capsules of version in 2015 or drops respectively
It is fixed), for vitamin A or D in per a collection of biased sample, during with its June content divided by content at 0 month multiplied by with 100% institute
Obtain percentage, the remaining percentage that vitamin A or D are postponed at through 40 DEG C-June in as this batch mixture;Result shows, right
Mix gained mixture with vitaminAD micropill in vitamin micro pill a obtained in example 1 above -5, their vitamin A is residual
In the range of 97.4~99.1%, vitamin D remnants percentages show this to remaining percentage in the range of 97.1~99.2%
Vitamin A and D in a little mixtures are respectively provided with excellent stability;In addition, including 8 kinds of amino to embodiment 1-5 gained simultaneously
Acid and 11 kinds of vitamin micro pill capsule agent carry out above-mentioned 40 DEG C-June dispose and determine vitamin A, D remnants percentages, as a result tie up
In the range of 97.6~99.2%, vitamin D remnants percentages are in 97.2~99.0% scopes for raw element A remnants percentages
It is interior;This shows, vitaminAD micropill individually with vitamin micro pill a or when jointly mixing with remaining 6 kinds of micropill, wherein tieing up
The stability of raw element A, D is presented essentially identical result.Then, the vitaminAD microballon produced purchased from RIKEN CORPORATION is used
(Riken Dry AD-B 100/10P, by Riken Vitamin Co., Ltd.'s imports to China, contain in every 1 gram of microballon
Vitamin A is 10 million international units, and the plain element D2 of dimension is 1 million international units), it is micro- with the gained vitamin of example 1 above -5 respectively
Ball a is according to the two ratio mixing in capsule formula, then the mixture is put 40 DEG C of placement June, mixed when determining 0 month and during June
Vitamin A content and vitamin D content are (respectively according to Chinese Pharmacopoeia two vitaminAD soft capsules of version in 2015 or drops in compound
In contained method determine), for vitamin A or D in per a collection of biased sample, content is divided by content at 0 month during with its June
Multiplied by with 100% gained percentage, the remaining percentage that vitamin A or D are postponed at through 40 DEG C-June in as this batch mixture
Number;Result shown, institute is mixed with Riken Dry AD-B 100/10P for vitamin micro pill a obtained in example 1 above -5
Mixture is obtained, in the range of 86.6~89.4%, vitamin D remnants percentages exist their vitamin A remnants percentages
In the range of 83.6~88.7%, show that vitamin A and D stability in these mixtures are undesirable;In addition, making the Riken
Dry AD-B 100/10P such as replace at the vitaminAD micropill in the embodiment 1-5 of weight respectively, capsule are made, while carrying out
40 DEG C-June disposes and determines vitamin A, D remnants percentages, and as a result vitamin A remnants percentages are in 87.1~88.9% models
In enclosing, vitamin D remnants percentages are in the range of 84.6~89.3%;This shows, commercially available Riken Dry AD-B 100/
10P individually with vitamin micro pill a or when jointly mixing with remaining 6 kinds of micropill, wherein vitamin A, the stability of D are paid no attention to
Think.Followed by according to the method for disposal of above-mentioned 40 DEG C-June, the five kinds of vitaminADs investigated obtained by embodiment of the present invention 1-5 are micro-
The stability of ball and commercially available Riken Dry AD-B 100/10P, determines their vitamin A remnants percentages and dimension respectively
Raw element D remnants percentages, as a result show that the vitamin A remnants percentages and vitamin D of this 6 batches of vitaminAD micropill/microballons are residual
Remaining percentage is in the range of 97.9~99.4%.The remaining percentage of vitamin A or vitamin D and following experiment in this experiment
In " labelled amount " have different implications, the two with reference to difference from without positive connection.
Comprising 8 kinds of amino acid and 11 kinds of loaded national drug standards of vitamin micro pill capsule agent, its standard No. is WS1-
(X-307) -2004Z, the standard is applied to the present invention and includes 8 kinds of amino acid and 11 kinds of vitamin micro pill capsule agent, and is applicable
VitaminAD micropill replaces with Japan's reason and grinds the capsule produced obtained by vitaminAD microballon in capsule of the present invention;In the present invention
Literary embodiment 1-5 gained capsule shines the standard detection, it has been found that indices meet standard regulation.
Test example 2:
In the present invention, term micropill refers to piller of the diameter between 0.05mm~1.5mm, and preferably diameter exists
Piller between 0.1mm~1.2mm.This bead can be spherical or almost spherical.In the present invention, term " approximate ball
Shape " refers to that the minor axis/draw ratio of piller is (0.2~1):1, preferably (0.5~1):1.In embodiment hereof 1-5, preparation it is complete
Minor axis/the draw ratio of 7 kinds of portion micropill, after measured, in (0.5~1):In the range of 1, the obtained vitaminAD of such as present invention
Minor axis/the draw ratio of micropill reaches after measured can be readily controlled in (0.9~1):In the range of 1, as noted above by tune
Whole technological parameter can be readily available micropill of the average major diameter in the range of 0.2~1.2mm, for example, can be readily available short
The parameters such as footpath/draw ratio, the major diameter micropill essentially identical with commercially available vitaminAD microballon.For example, it is believed that commercially available vitamin
AD microballons minor axis/draw ratio is after measured up to 0.94:1, and major diameter is between 0.4~0.6mm.
As described above, the present invention can be readily available averagely when vitaminAD micropill is prepared by adjusting process parameter
Particle diameter in 200~1200 μ ms, particularly micropill of its average grain diameter in 300~900 μ ms.For example, by step
Suddenly the intensity adjustment of emulsification procedure can obtain desired average grain diameter in (2), such as can obtain flat when emulsion strength is high
The smaller micropill of equal particle diameter, and the average grain diameter of gained micropill is than larger when emulsion strength is relatively low.With average grain diameter ±
Micropill number in the range of 50 μm accounts for the percentage of total micropill number for index to judge the width of micropill size distribution, and display is real
In applying each processing step that vitaminAD micropill is prepared in a 1-5, technological parameter therein is made to meet present invention provide that it is suitable
After adjustment, this percentage is all higher than 70%, and both greater than 80% particularly in the case of the overwhelming majority, this performance shows this hair
Bright micropill has very narrow particle size distribution.
When example 1 above -5 prepares vitaminAD micropill, by drying (40~60 DEG C of hot air dryings of step (4)
It is dry), can cause that the moisture (in terms of 105 DEG C of dryings, 2 hours gained loss on drying results) in the micropill is respectively less than
7%.In addition, it has been found that by determining the possible remaining organic solvent of gained vitaminAD micropill after this drying, as a result showing
These organic solvents cannot be detected with vapor phase method, that is, be below its test limit, show present invention gained vitaminAD micropill
The basic residual organic solvent introduced without technique.
Claims (10)
1. a kind of vitaminAD micropill, wherein comprising vitamin A and calciferol;2~200,000 I.U. are included in its every 1 gram of micropill
Vitamin A, 0.2~20,000 I.U. vitamin Ds2。
2. vitaminAD micropill according to claim 1, it is characterised in that:
5~150,000 I.U. vitamin As are included in its every 1 gram of micropill;
8~120,000 I.U. vitamin As are included in its every 1 gram of micropill;
100,000 I.U. vitamin As are included in its every 1 gram of micropill;
0.5~1.5 ten thousand I.U. vitamin Ds are included in its every 1 gram of micropill2;
0.8~1.2 ten thousand I.U. vitamin Ds are included in its every 1 gram of micropill2;
10,000 I.U. vitamin Ds are included in its every 1 gram of micropill2;And/or
The vitamin A be with vitamin A or Retinol Palmitate or vitamine A acetate or vitamin A its
The form of its ester is added in the vitaminAD micropill.
3. vitaminAD micropill according to claim 1, it is characterised in that:
Wherein also contain edible vegetable oil such as corn oil, soybean oil, peanut oil, sunflower oil etc.;
100~200mg of edible vegetable oil, such as such as 120~160mg, 130~150mg are included in its every 1 gram of micropill;
Wherein also contain sorbitan fatty acid ester, such as span20 (i.e. Arlacel-20), span40 (i.e. Arlacel-40),
Span60 (i.e. Arlacel-60), span65 (i.e. Arlacel-65), span80 (i.e. Arlacel-80), span85 (i.e. Arlacel-85);
2~20mg of sorbitan fatty acid ester, such as such as 2~15mg, 2~12mg are included in its every 1 gram of micropill;
Wherein also contain gelatin;
400~700mg of gelatin, such as such as 500~650mg, 550~600mg are included in its every 1 gram of micropill;
Wherein also contain sucrose;
100~300mg of sucrose, such as such as 150~250mg, 180~240mg are included in its every 1 gram of micropill;
Wherein also contain preservative;In one embodiment, the preservative is selected from Sodium Benzoate, dehydroactic acid sodium, sorb
Acid, potassium sorbate, mud parker methyl ester, mud moor gold ethyl ester, the golden propyl ester of mud pool and combinations thereof;
1~5mg of anti-corrosion, such as such as 1.5~3mg, 2~3mg are included in its every 1 gram of micropill;
Wherein contain Sodium Benzoate, 0.2~2mg of Sodium Benzoate, such as 0.5~1.5mg, such as 0.75 are included in every 1 gram of micropill
~1mg;And/or
Wherein contain dehydroactic acid sodium, in every 1 gram of micropill comprising 0.5~5mg of dehydroactic acid sodium, such as 1~3mg, such as 1.2~
2mg。
4. vitaminAD micropill according to claim 1, it is prepared according to the method for comprising the following steps:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing are made into dissolving, obtains oiliness liquid;
Separately gelatin and sucrose are dissolved in the water, preservative is added, is stirred to dissolve, obtain aqueous solution;
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing obtains emulsion;
(3) in step (2) gained emulsion being dropped into the solidified oil of stirring, cooling coagulates the emulsion droplet being dispersed in the solidified oil
Gu to form piller, piller is then leached,
(4) gained piller organic solvent washing is dried with removing the solidified oil on surface, obtains final product vitaminAD micropill.
5. vitaminAD micropill according to claim 1, it is characterised in that:
In step (1), described oiliness liquid is obtained at a temperature of 35~100 DEG C, is made e.g. at a temperature of 35~80 DEG C
;
In step (1), described aqueous solution is obtained at a temperature of 40~100 DEG C, is made e.g. at a temperature of 50~85 DEG C
;
The temperature that step (2) medium oil liquid mixes with aqueous solution is 50~100 DEG C, such as 60~80 DEG C;
Solidified oil described in step (3) is selected from vegetable oil, dimeticone, atoleine or its combination;For example, the vegetable oil
Such as edible vegetable oil such as corn oil, soybean oil, peanut oil, sunflower oil;
The temperature of the solidified oil stirred described in step (3) is 35~100 DEG C, such as 35~70 DEG C;
Less than 40 DEG C of temperature is cooled in step (3), for example, is cooled to less than 35 DEG C of temperature, for example, be cooled to less than 30 DEG C
Temperature;
Organic solvent described in step (4) is selected from ethanol, petroleum ether, isopropanol etc..
6. vitaminAD micropill according to claim 1, it is characterised in that:
Its moisture, less than 10%, is, for example, less than 7% in terms of loss on drying;The loss on drying is in 105 DEG C of dryings 2 hours
What measure was obtained;
In 200~1200 μ ms, particularly its average grain diameter is in 300~900 μ ms for its average grain diameter;And/or
Micropill number wherein in the range of average grain diameter ± 50 μm accounts for more than the 60% of total micropill number, for example, account for total micropill number
More than 70%, for example account for more than the 80% of total micropill number.
7. the method for preparing vitaminAD micropill, it comprises the following steps:
(1) vitamin A, calciferol, edible vegetable oil, sorbitan fatty acid ester mixing are made into dissolving, obtains oiliness liquid;
Separately gelatin and sucrose are dissolved in the water, preservative is added, is stirred to dissolve, obtain aqueous solution;
(2) in step (1) gained oiliness liquid being added into the aqueous solution of stirring, stirring mixing obtains emulsion;
(3) in step (2) gained emulsion being dropped into the solidified oil of stirring, cooling coagulates the emulsion droplet being dispersed in the solidified oil
Gu to form piller, piller is then leached,
(4) gained piller organic solvent washing is dried with removing the solidified oil on surface, obtains final product vitaminAD micropill.
8. method according to claim 7, it is characterised in that:
2~200,000 I.U. vitamin As are included in every 1 gram of the vitaminAD micropill, such as 5~15 are included in its every 1 gram of micropill
8~120,000 I.U. vitamin As are included in ten thousand I.U. vitamin As, such as its every 1 gram of micropill, such as 10 are included in its every 1 gram of micropill
Ten thousand I.U. vitamin As;
The vitamin A be with vitamin A or Retinol Palmitate or vitamine A acetate or vitamin A its
The form of its ester is added in the vitaminAD micropill;
0.2~20,000 I.U. vitamin Ds are included in every 1 gram of the vitaminAD micropill2, such as in its every 1 gram of micropill comprising 0.5~
1.5 ten thousand I.U. vitamin Ds2, such as 0.8~1.2 ten thousand I.U. vitamin Ds are included in its every 1 gram of micropill2, such as its every 1 gram of micropill
In include 10,000 I.U. vitamin Ds2;
The edible vegetable oil such as corn oil, soybean oil, peanut oil, sunflower oil etc.;
In every 1 gram of the vitaminAD micropill comprising 100~200mg of edible vegetable oil, such as 120~160mg, such as 130~
150mg;
The sorbitan fatty acid ester, such as span20, span40, span60, span65, span80, span85;
In every 1 gram of the vitaminAD micropill comprising 2~20mg of sorbitan fatty acid ester, such as 2~15mg, such as 2~
12mg;
400~700mg of gelatin, such as such as 500~650mg, 550~600mg are included in every 1 gram of the vitaminAD micropill;
100~300mg of sucrose, such as such as 150~250mg, 180~240mg are included in every 1 gram of the vitaminAD micropill;
The preservative be selected from Sodium Benzoate, dehydroactic acid sodium, sorbic acid, potassium sorbate, mud parker methyl ester, mud moor gold ethyl ester,
Golden propyl ester of mud pool and combinations thereof;
1~5mg of preservative, such as such as 1.5~3mg, 2~3mg are included in every 1 gram of the vitaminAD micropill;
0.2~2mg of Sodium Benzoate, such as such as 0.5~1.5mg, 0.75~1mg are included in every 1 gram of the vitaminAD micropill;
0.5~5mg of dehydroactic acid sodium, such as such as 1~3mg, 1.2~2mg are included in every 1 gram of the vitaminAD micropill;
In step (1), described oiliness liquid is obtained at a temperature of 35~100 DEG C, is made e.g. at a temperature of 35~80 DEG C
;
In step (1), described aqueous solution is obtained at a temperature of 40~100 DEG C, is made e.g. at a temperature of 50~85 DEG C
;
The temperature that step (2) medium oil liquid mixes with aqueous solution is 50~100 DEG C, such as 60~80 DEG C;
Solidified oil described in step (3) is selected from vegetable oil, dimeticone, atoleine or its combination;For example, the vegetable oil
Such as edible vegetable oil such as corn oil, soybean oil, peanut oil, sunflower oil;
The temperature of the solidified oil stirred described in step (3) is 35~100 DEG C, such as 35~70 DEG C;
Less than 40 DEG C of temperature is cooled in step (3), for example, is cooled to less than 35 DEG C of temperature, for example, be cooled to less than 30 DEG C
Temperature;
Organic solvent described in step (4) is selected from ethanol, petroleum ether, isopropanol etc.;
The dry moisture being so that in the micropill is, for example, less than less than 10% in terms of loss on drying described in step (4)
7%;Such as described loss on drying is determined and obtained for 2 hours in 105 DEG C of dryings;
In 200~1200 μ ms, particularly its average grain diameter is 300 for vitaminAD micropill its average grain diameter obtained by it
In~900 μ ms;
VitaminAD micropill obtained by it, wherein the micropill number in the range of average grain diameter ± 50 μm accounts for total micropill number
More than 60%, more than the 70% of total micropill number is for example accounted for, for example account for more than the 80% of total micropill number.
9. a kind of capsule, it includes 7 kinds of spherical or almost spherical micropills, and wraps up the capsule shells of these micropills, described 7
8 kinds of amino acid and 11 kinds of vitamins are included in kind micropill, and 7 kinds of micropills and its weight proportion are in parts by weight:
Wherein:
The vitaminAD micropill is as described in claim any one of 1-6, or as described in claim any one of 7-8
Obtained in method;
Described thiamine mononitrate micropill is included in parts by weight:
Described vitamin micro pill a is included in parts by weight:
Described amino acid micropill a is included in parts by weight:
Described vitamin micro pill b is included in parts by weight:
Described amino acid micropill b is included in parts by weight:
Described vitamin C micro-pill is included in parts by weight:
10. obtained in vitaminAD micropill described in any one of claim 1-6, or claim 7-8 any one methods describeds
Purposes of the vitaminAD micropill in compound amino acid capsule is prepared, wherein the compound amino acid capsule includes following weight ratio
The component of example:
The vitamin A and calciferol are present in the vitaminAD micropill.
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CN109432070A (en) * | 2018-11-09 | 2019-03-08 | 深圳万和制药有限公司 | The preparation method and vitaminAD pellet of high uniformity vitaminAD pellet |
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CN1391485A (en) * | 1999-12-23 | 2003-01-15 | 阿方蒂动物营养素股份有限公司 | Particulate vitamin composition |
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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2017
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Publication number | Priority date | Publication date | Assignee | Title |
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CN1391485A (en) * | 1999-12-23 | 2003-01-15 | 阿方蒂动物营养素股份有限公司 | Particulate vitamin composition |
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 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN109432070A (en) * | 2018-11-09 | 2019-03-08 | 深圳万和制药有限公司 | The preparation method and vitaminAD pellet of high uniformity vitaminAD pellet |
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