CN105708829A - Complex vitamin and amino acid oral liquid as well as preparation method and application thereof - Google Patents
Complex vitamin and amino acid oral liquid as well as preparation method and application thereof Download PDFInfo
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- CN105708829A CN105708829A CN201610039862.4A CN201610039862A CN105708829A CN 105708829 A CN105708829 A CN 105708829A CN 201610039862 A CN201610039862 A CN 201610039862A CN 105708829 A CN105708829 A CN 105708829A
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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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
Abstract
The invention belongs to the field of a health care product, and in particular relates to a complex vitamin and amino acid oral liquid as well as a preparation method and application thereof. The complex vitamin and amino acid oral liquid provided by the invention mainly consists of isoleucine, threonine, valine, aspartic acid, arginine hydrochloride, lysine hydrochloride, phenylalanine, methionine, leucine, tryptophan, nicotinamide, vitamin B1, vitamin B2, vitamin B6 and water. The complex vitamin and amino acid oral liquid provided by the invention is reasonable in compatibility of various components, and is capable of effectively keeping nutrient balance in human bodies; and meanwhile, the oral liquid also has functions of boosting immunity of organism and relieving fatigue of the human bodies. At the same time, upon tests, the complex vitamin and amino acid oral liquid has a certain effect on improving idiopathic pulmonary fibrosis.
Description
Technical field
The invention belongs to field of health care products, be specifically related to a kind of compound vitamin amino acids oral-liquor and preparation method thereof and
Application.
Background technology
Aminoacid and vitamin are to maintain base substance necessary to human normal vital movement and health.Aminoacid is egg
The ultimate unit of white matter molecule, has close relationship with biological vital movement, and it has special physiology merit in human body
Can, it is one of indispensable nutritional labeling in organism.The aminoacid constituting human body mainly has 20 kinds, and wherein having 8 kinds is people
Body can not synthesize, it is necessary to draws from food, is referred to as " essential amino acids ", and remaining is " non essential amino acid ".Vitamin is also
It is the nutrient of needed by human, is divided into fatsoluble vitamin and water soluble vitamin raw according to its dissolubility in lipid solvent or water
Element two big classes, fatsoluble vitamin includes vitamin A, vitamin D, vitamin E and vitamin K, and remaining is water soluble vitamins.
Vitamin B complex has the normal physiological function safeguarding nervous tissue and brain mostly, improves memory and eases up the effect of decompression force,
The growth and development process of the mankind plays a very important role.
Aminoacid can be with vitamin generation synergism, and vitamin can effectively improve aminoacid absorption in vivo,
Improve cell to amino acid whose bioavailability, promote the synthesis of protein, thus improve the conjunction of human amino acid and protein
Become and metabolism.Meanwhile, aminoacid also can promote absorption and the utilization of vitamin, can more effectively reach allaying tiredness and raising
The effect of body immunity.
At present, the amino acid whose joint product of vitamin is more and more diversified on the market.Chinese patent CN100402034C is public
A kind of aminoacids complex and vitamine capsule preparation and preparation method thereof, described aminoacids complex and vitamine capsule system are opened
Agent comprises aminoacid coated granule and vitamin particles, and wherein said aminoacid relies ammonia selected from isoleucine, leucine, hydrochloric acid
Acid, phenylalanine, methionine, threonine, tryptophan, valine and arginine hydrochloride；Described vitamin is selected from vitamin B1Nitre
Hydrochlorate, vitamin B2, vitamin B6, Vitamin E acetate and nicotiamide.The aminoacids complex prepared and vitamine capsule
Preparation has holding human nutrition balance, enhancing human body immunity power and the function of alleviation human-body fatigue.
Chinese patent CN100364528C discloses a kind of compound amino acid vitamin dispersion tablet and preparation method thereof, described
Compound amino acid vitamin dispersion tablet be made up of white and orange double-layer tablet, described white tablets by isoleucine, leucine,
The raw material compositions such as lysine hydrochloride, phenylalanine, threonine, valine, methionine, arginine hydrochloride, glutamic acid and glycine,
Described orange by vitamin B1Nitrate, vitamin B2, vitamin B6, the raw material composition such as vitamin E and nicotiamide.It is prepared into
To compound amino acid vitamin dispersion tablet there is enhancing body immunity, and can be used for the hypoproteinemia that various disease is caused
The auxiliary treatment of disease.
But, the amino acid whose joint product of current vitamin is made generally in solid preparation to solve the problem of its stability,
But for old people and child, solid preparation existence is difficult to take, absorb slow defect.Oral liquid formulations can be effectively
Solve drawbacks described above.Therefore, research and develop out a kind of reasonable recipe, absorb fast, the vitamin ammonia of taking convenience, good stability
Base acid joint product is still the focus of current research.
Idiopathic pulmonary fibrosis (Idiopathic Pulmonary Fibrosis, IPF) is that a kind of chronic progressive external is sent out
Exhibition, pathological changes is confined to pulmonary, histopathology and high-resolution ct and is shown as the disease of plain edition interstitial pneumonia type feature.Draw
The reason playing idiopathic pulmonary fibrosis has smoking, the exposure of environment occupational factor, microorganism infection, gastroesophageal reflux and inherited genetic factors
Deng.The poor prognosis of idiopathic pulmonary fibrosis, mortality rate is higher.The drug main for the treatment of idiopathic pulmonary fibrosis to have sugared skin at present
Matter hormone, colchicine, ciclosporin A, acetyl cysteine, anticoagulant, pirfenidone, sldenafil and imatinib etc., but
Idiopathic pulmonary fibrosis is the most poor to the therapeutic response of hormone and above-mentioned various medicine, there is no at present and can effectively treat
The medicine of idiopathic pulmonary fibrosis disease.
Summary of the invention
In order to solve, vitamin amino acids oral-liquor mouthfeel in prior art is poor, the defect of poor stability, the mesh of the present invention
One of be to provide a kind of compound vitamin amino acids oral-liquor and preparation method thereof, to solve drawbacks described above.
The invention provides a kind of compound vitamin amino acids oral-liquor, including following component and parts by weight thereof:
Isoleucine 5.5-8.5 part, threonine 4.5-7 part, valine 4.5-7 part, aspartic acid 4.5-7 part, arginine hydrochloride
3-4.5 part, lysine hydrochloride 3-4.5 part, phenylalanine-3,4-quinone-4.5 parts, methionine 3-4.5 part, leucine 1.5-2.5 part, color ammonia
Acid 0.46-0.8 part, nicotiamide 0.32-0.48 part, vitamin B10.07-0.12 part, vitamin B20.032-0.048 part, dimension
Raw element B60.032-0.048 part, water adds to 1000 parts.
Further, described compound vitamin amino acids oral-liquor includes following component and parts by weight thereof:
Isoleucine 7.1 parts, threonine 5.9 parts, valine 5.87 parts, aspartic acid 5.7 parts, arginine hydrochloride 5 parts, hydrochloric acid rely
Propylhomoserin 4.62 parts, phenylalanine-3,4-quinone .74 part, methionine 3.7 parts, leucine 1.86 parts, tryptophan 0.66, nicotiamide 0.4 part, dimension
Raw element B10.1 part, vitamin B20.04 part, vitamin B60.04 part, water adds to 1000 parts.
Further, described compound vitamin amino acids oral-liquor also comprises the following components and parts by weight:
Stabilizer 2-8 part, erythritol 1-4 part, assorted fruital essence 0.5-1.5 part, cyclamate 0.1-1 part, raspberry essence 0.1-1
Part, sucralose 0.1-1 part, acesulfame potassium 0.1-0.5 part, Herba Menthae 0.001-0.05 part and neotame 0.001-0.05 part.
Further, described compound vitamin amino acids oral-liquor includes following component and parts by weight thereof:
Isoleucine 7.1 parts, threonine 5.9 parts, valine 5.87 parts, aspartic acid 5.7 parts, arginine hydrochloride 5 parts, hydrochloric acid rely
Propylhomoserin 4.62 parts, phenylalanine-3,4-quinone .74 part, methionine 3.7 parts, leucine 1.86 parts, tryptophan 0.66, nicotiamide 0.4 part, dimension
Raw element B10.1 part, vitamin B20.04 part, vitamin B6 0.04 part, stabilizer 5.5 parts, erythritol 2.48 parts, assorted fruital
Essence 0.96 part, cyclamate 0.48 part, raspberry essence 0.24 part, sucralose 0.225 part, acesulfame potassium 0.172 part, Herba Menthae
0.018 part, neotame 0.01 part, water adds to 1000 parts.
Further, described stabilizer is by sodium citrate, sodium D-isoascorbate and xanthan gum 0.8-1.5 by weight:
0.006-0.015:0.6-1 forms.
Further, described stabilizer is by sodium citrate, sodium D-isoascorbate and xanthan gum 1:0.01 by weight:
0.8 composition.
The each component compatibility of compound vitamin amino acids oral-liquor that the present invention provides is reasonable, can effectively keep human body to seek
Support balance, the most also there is enhancing human body immunity power and alleviate the function of human-body fatigue.And prove through stability test, this
The compound vitamin amino acids oral-liquor of bright offer temperature be 40 ± 2 DEG C, relative humidity be RH75 ± 5% under conditions of store 6
Individual month, its active constituent content all met relevant regulations, was that active constituent content is high, and the vitamin aminoacid of good stability is combined
Product.
It addition, present invention also offers the preparation method of a kind of compound vitamin amino acids oral-liquor, comprise the following steps:
S1 takes the water ebuillition of heated 10-20min of half amount, is cooled to 70-80 DEG C, add isoleucine, threonine, valine,
Aspartic acid, arginine hydrochloride, lysine hydrochloride, phenylalanine, methionine, leucine, tryptophan, nicotiamide, vitamin
B1, vitamin B2And vitamin B6, stirring, to being completely dissolved, obtains mixed liquor I；
The mixed liquor I that step S1 is obtained by S2 is cooled to 30-40 DEG C, adds remaining water, obtains mixed liquor I I；
Mixed liquor I I that step S2 is obtained by S3 filters, embedding, and sterilizing 8-35min to obtain final product.
Further, described step S1 is additionally added stabilizer, erythritol, cyclamate, sucralose, acesulfame potassium, Herba Menthae
And neotame, add assorted fruital essence and raspberry essence after the cooling of described step S2.
Further, the sterilising temp in described step S3 is 110-121 DEG C.
In addition, the two of the purpose of the present invention are to provide described compound vitamin amino acids oral-liquor in preparation auxiliary
Application in treatment idiopathic pulmonary fibrosis health product.Inventor is found surprisingly that, the compound vitamin amino that the present invention provides
Acid oral liquid can significantly improve the alveolitis of idiopathic pulmonary fibrosis rat model, macrophage foam cell formation sample changes, fiber
The symptom such as cell activation and collagen fiber hyperplasia, has good improvement result to idiopathic pulmonary fibrosis, is more beneficial for special sending out
The rehabilitation of property pulmonary fibrosis patients.
Compared with prior art, the compound vitamin amino acids oral-liquor that the present invention provides has the advantage that
(1) each component compatibility of compound vitamin amino acids oral-liquor that the present invention provides is reasonable, can effectively keep human body to seek
Support balance, the most also there is enhancing human body immunity power and alleviate the function of human-body fatigue；
(2) the compound vitamin amino acids oral-liquor thing that the present invention provides is to be scattered in medium with molecularity, has dispersion
Degree is greatly, absorption is fast, drug effect plays rapidly and the effect little to gastrointestinal irritation, is a kind of vitamin meeting modern's requirement
Aminoacid joint product；
(3) the compound vitamin amino acids oral-liquor that the present invention provides can significantly improve idiopathic pulmonary fibrosis rat model
Alveolitis, macrophage foam cell formation sample change, fibrocyte activation and the symptom such as collagen fiber hyperplasia, to idiopathic pulmonary fibrosis
There is good improvement result, be more beneficial for the rehabilitation of idiopathic pulmonary fibrosis.
Detailed description of the invention
Below by way of the description of detailed description of the invention, the invention will be further described, but this is not the limit to the present invention
System, those skilled in the art are according to the basic thought of the present invention, and various modifications may be made or improves, but without departing from this
The basic thought of invention, the most within the scope of the present invention.Wherein, each component in the present invention is conventional commercial product, example
As: assorted fruital essence is purchased from Qi Huadun edible essence spice (Shanghai) Co., Ltd., model is DLQ-3450, and raspberry essence is purchased from
Dongguan City Hua Lin trade Co., Ltd, model is DLQ-0720.
Embodiment 1, a kind of compound vitamin amino acids oral-liquor
Described compound vitamin amino acids oral-liquor includes following component and parts by weight thereof:
Isoleucine 5.5 parts, threonine 4.5 parts, valine 4.5 parts, aspartic acid 4.5 parts, arginine hydrochloride 3 parts, hydrochloric acid rely
Propylhomoserin 3 parts, phenylalanine-3,4-quinone part, methionine 3 parts, leucine 1.5 parts, tryptophan 0.46 part, nicotiamide 0.32 part, vitamin B1
0.07 part, vitamin B20.032 part, vitamin B60.032 part, water adds to 1000 parts.
Preparation method:
S1 takes the water ebuillition of heated 15min of half amount, is cooled to 80 DEG C, adds isoleucine, threonine, valine, Radix Asparagi
Propylhomoserin, arginine hydrochloride, lysine hydrochloride, phenylalanine, methionine, leucine, tryptophan, nicotiamide, vitamin B1, dimension raw
Element B2And vitamin B6, stirring, to being completely dissolved, obtains mixed liquor I；
The mixed liquor I that step S1 is obtained by S2 is cooled to 30 DEG C, adds remaining water, obtains mixed liquor I I；
Mixed liquor I I that step S2 is obtained by S3 is through filtering, and embedding, at temperature is 115 DEG C, sterilizing 30min, to obtain final product.
Embodiment 2, a kind of compound vitamin amino acids oral-liquor
Described compound vitamin amino acids oral-liquor includes following component and parts by weight thereof:
Isoleucine 7.1 parts, threonine 5.9 parts, valine 5.87 parts, aspartic acid 5.7 parts, arginine hydrochloride 5 parts, hydrochloric acid rely
Propylhomoserin 4.62 parts, phenylalanine-3,4-quinone .74 part, methionine 3.7 parts, leucine 1.86 parts, tryptophan 0.66, nicotiamide 0.4 part, dimension
Raw element B10.1 part, vitamin B20.04 part, vitamin B60.04 part, water adds to 1000 parts.
Preparation method is similar to Example 1.
Embodiment 3, a kind of compound vitamin amino acids oral-liquor
Described compound vitamin amino acids oral-liquor includes following component and parts by weight thereof:
Isoleucine 5.5 parts, threonine 4.5 parts, valine 4.5 parts, aspartic acid 4.5 parts, arginine hydrochloride 3 parts, hydrochloric acid rely
Propylhomoserin 3 parts, phenylalanine-3,4-quinone part, methionine 3 parts, leucine 1.5 parts, tryptophan 0.46 part, nicotiamide 0.32 part, vitamin B1
0.07 part, vitamin B20.032 part, vitamin B60.032 part, stabilizer 2 parts, erythritol 1 part, assorted fruital essence 0.5 part,
Cyclamate 0.1 part, raspberry essence 0.1 part, sucralose 0.1 part, acesulfame potassium 0.1 part, Herba Menthae 0.001 part, neotame 0.001
Part, water adds to 1000 parts；Described stabilizer is by sodium citrate, sodium D-isoascorbate and xanthan gum 0.8:0.015 by weight:
1 composition.
Preparation method:
S1 takes the water ebuillition of heated 15min of half amount, is cooled to 80 DEG C, adds isoleucine, threonine, valine, Radix Asparagi
Propylhomoserin, arginine hydrochloride, lysine hydrochloride, phenylalanine, methionine, leucine, tryptophan, nicotiamide, vitamin B1, dimension raw
Element B2, vitamin B6, stabilizer, erythritol, cyclamate, sucralose, acesulfame potassium, Herba Menthae and neotame, stirring is to the most molten
Solve, obtain mixed liquor I；
The mixed liquor I that step S1 is obtained by S2 is cooled to 30 DEG C, adds assorted fruital essence and raspberry essence, stirs, and add
Enter remaining water, obtain mixed liquor I I；
Mixed liquor I I that step S2 is obtained by S3 is through filtering, and embedding, at temperature is 115 DEG C, sterilizing 30min, to obtain final product.
Embodiment 4, a kind of compound vitamin amino acids oral-liquor
Described compound vitamin amino acids oral-liquor includes following component and parts by weight thereof:
Isoleucine 7.1 parts, threonine 5.9 parts, valine 5.87 parts, aspartic acid 5.7 parts, arginine hydrochloride 5 parts, hydrochloric acid rely
Propylhomoserin 4.62 parts, phenylalanine-3,4-quinone .74 part, methionine 3.7 parts, leucine 1.86 parts, tryptophan 0.66, nicotiamide 0.4 part, dimension
Raw element B10.1 part, vitamin B20.04 part, vitamin B60.04 part, stabilizer 5.5 parts, erythritol 2.48 parts, assorted fruital
Essence 0.96 part, cyclamate 0.48 part, raspberry essence 0.24 part, sucralose 0.225 part, acesulfame potassium 0.172 part, Herba Menthae
0.018 part, neotame 0.01 part, water adds to 1000 parts；Described stabilizer is pressed by sodium citrate, sodium D-isoascorbate and xanthan gum
Weight ratio 1:0.01:0.8 forms.
Preparation method is similar to Example 3.
Embodiment 5, a kind of compound vitamin amino acids oral-liquor
Described compound vitamin amino acids oral-liquor includes following component and parts by weight thereof:
Isoleucine 8.5 parts, threonine 7 parts, valine 7 parts, aspartic acid 7 parts, arginine hydrochloride 4.5 parts, lysine hydrochloride
4.5 parts, phenylalanine 4.5 parts, methionine 4.5 parts, leucine 2.5 parts, tryptophan 0.8 part, nicotiamide 0.48 part, vitamin B1
0.12 part, vitamin B20.048 part, vitamin B60.048 part, stabilizer 8 parts, erythritol 4 parts, assorted fruital essence 1.5 parts,
Cyclamate 1 part, raspberry essence 1 part, sucralose 1 part, acesulfame potassium 0.5 part, Herba Menthae 0.05 part, neotame 0.05 part, water adds to
1000 parts；Described stabilizer is made up of by weight 1.5:0.006:0.6 sodium citrate, sodium D-isoascorbate and xanthan gum.
Preparation method is similar to Example 3.
Comparative example 1, a kind of compound vitamin amino acids oral-liquor
Component and the parts by weight thereof of described compound vitamin amino acids oral-liquor are: described stabilizer is that sodium citrate, D-are different
Sodium ascorbate and xanthan gum form by weight 1.6:0.005:0.5, remaining component such as embodiment 2.
Preparation method is similar to Example 3.
Comparative example 2, a kind of compound vitamin amino acids oral-liquor
Component and the parts by weight thereof of described compound vitamin amino acids oral-liquor are: described stabilizer is by sodium citrate and xanthan
Glue forms by weight 1:0.8, remaining component such as embodiment 2.
Preparation method is similar to Example 3.
Comparative example 3, a kind of compound vitamin amino acids oral-liquor
Described compound vitamin amino acids oral-liquor includes following component and parts by weight thereof:
Isoleucine 7.1 parts, threonine 5.9 parts, valine 5.87 parts, arginine hydrochloride 5 parts, lysine hydrochloride 4.62 parts, benzene
Alanine 3.74 parts, methionine 3.7 parts, leucine 1.86 parts, tryptophan 0.66, nicotiamide 0.4 part, vitamin B1 0.1 part, dimension
Raw element B20.04 part, vitamin B6 0.04 part, stabilizer 5.5 parts, erythritol 2.48 parts, assorted fruital essence 0.96 part, cyclamate
0.48 part, raspberry essence 0.24 part, sucralose 0.225 part, acesulfame potassium 0.172 part, Herba Menthae 0.018 part, neotame 0.01 part,
Water adds to 1000 parts；Described stabilizer is by sodium citrate, sodium D-isoascorbate and xanthan gum 1:0.01:0.8 group by weight
Become.
Preparation method is similar to Example 3.
Test example one, the quality testing test of compound vitamin amino acids oral-liquor
1, test material: embodiment 1, embodiment 2, embodiment 3, embodiment 4 and the compound vitamin aminoacid of embodiment 5 preparation
Oral liquid.
2, test method:
Detection embodiment 1, embodiment 2, embodiment 3, embodiment 4 and the compound vitamin amino acids oral-liquor of embodiment 5 preparation
Appearance character, soluble solid and microbiological indicator.Wherein, the detection of soluble solid: advise with reference to GB/T 12143
Fixed method detection, microbiological indicator includes: total plate count, coliform, mycete, yeast, staphylococcus aureus and sramana
Salmonella, the detection of total plate count: with reference to the method detection of GB 4789.2 regulation, the detection of coliform: with reference to GB 4789.3
The method detection that (MPN counting method) specifies, mycete, the detection of yeast: with reference to the method detection of GB 4789.15 regulation, golden yellow
Staphylococcus, the detection of Salmonella: with reference to the method detection of GB 4789.4, GB 4789.10 regulation.
3, result of the test:
Result of the test is as shown in table 1.
The quality testing data of table 1 compound vitamin amino acids oral-liquor
As shown in Table 1, compound vitamin amino acids oral-liquor outward appearance prepared by embodiment of the present invention 1-5 is light yellow, free from extraneous odour,
The exogenous impurity being visible by naked eyes, its soluble solid and microbiological indicator all meet relevant regulations simultaneously, are a kind of safety
Property high, the vitamin aminoacid joint product that product quality is high.
Test example two, the stability test of compound vitamin amino acids oral-liquor
1, test material: embodiment 3, embodiment 4, embodiment 5, comparative example 1 and the compound vitamin aminoacid of comparative example 2 preparation
Oral liquid.
2, test method:
Compound vitamin amino acids oral-liquor prepared by embodiment 3, embodiment 4, embodiment 5, comparative example 1 and comparative example 2 is put
In temperature be 40 ± 2 DEG C, relative humidity be RH75 ± 5%, avoid light direct projection under conditions of store 6 months, respectively at 0,1,2,
3, within 6 months, it is sampled investigating, checks the active constituent content of compound vitamin amino acids oral-liquor.
Wherein: isoleucine, threonine, valine, aspartic acid, arginine hydrochloride, lysine hydrochloride, phenylpropyl alcohol ammonia
Acid, methionine, leucic assay: the method specified with reference to GB/T 5009.124 " amino acid whose mensuration in food " is surveyed
Fixed；Vitamin B1Assay: with reference to GB/T 5009.84, " in food, thiamine presses (vitamin B1) mensuration " specify
Method measures；Vitamin B2Assay: survey with reference to GB/T 5009.85 " mensuration of riboflavin in the food " method that specifies
Fixed；Vitamin B6, the assay of nicotiamide: " in health food, thiamine hydrochloride, hydrochloric acid pyrrole are trembled with reference to GB/T 5009.197
The mensuration of alcohol, nicotinic acid, nicotiamide and caffeine " method that specifies measures；The assay of tryptophan uses high performance liquid chromatography
Instrument measures, and chromatographic column is: octadecyl silane post, and flowing is mutually: phosphate buffer: methanol=1000:176.
Compound vitamin amino acids oral-liquor active constituent content judgment criteria is as shown in table 2, the compound vitamin of detection
Amino acids oral-liquor active constituent content in the range of table 2 specifies for qualified, exceed or fall below then for defective.
Table 2 compound vitamin amino acids oral-liquor active constituent content judgment criteria table
3, result of the test:
Result of the test is as shown in table 3.
The stability test of table 3 compound vitamin amino acids oral-liquor
As shown in Table 3, the compound vitamin amino acids oral-liquor that prepared by embodiment of the present invention 3-5 temperature be 40 ± 2 DEG C, relatively
Humidity is to store 6 months under conditions of RH75 ± 5%, the content of its each effective ingredient all in the range of above-mentioned table 2 specifies, and
The stable effective ingredients of the compound vitamin amino acids oral-liquor of comparative example 1 and comparative example 2 preparation is all prepared than embodiment 3-5
The weak effect of compound vitamin amino acids oral-liquor, illustrate that the present invention provides by sodium citrate, sodium D-isoascorbate and
The stabilizer of xanthan gum composition can effectively increase stablizing of compound vitamin amino acids oral-liquor in the range of certain proportion
Property.
Test example three, the test of alleviating physical fatigue of compound vitamin amino acids oral-liquor
1, subjects: choosing 160 SPF level Kunming female white mice of kind, 68 week old, body weight is 18g-22g, by Guangdong Province
Medical experiment animal center provides.
2, test material: the compound vitamin amino acids oral-liquor of embodiment 4 preparation.
3, test method:
3.1,160 white mice after quarantining in laboratory conditions three days are randomly divided into I, II, III, IV and criticize, 40 every batch
Animal is randomly divided into four groups, respectively matched group, low dose group, middle dosage group and high dose group, basic, normal, high three dosage groups
Dosage be embodiment 4 preparation the 4.17 of compound vitamin amino acids oral-liquor, 8.33,25.00ml/kg BW, this test is adopted
Test with 2 times of concentrated solutions, conversion post dose be 2.08,4.17,12.50 ml/kg BW, be equivalent to human body recommended amounts 5,
10,30 times, matched group is separately set.
3.2, compound vitamin amino acids oral-liquor is concentrated 2 times at Rotary Evaporators (60V, under 0.1 atmospheric pressure), examination
Measure when testing concentrating sample 6.2,12.5,37.5ml, be configured to the sample liquid of 60ml respectively with pure water, for basic, normal, high three agent
Amount treated animal gavage uses.Being gavage to quadrat method, every day gives tested material, matched group by 0.2ml/10g BW amount gavage animal
Every day, gavage gave 0.2ml/10gBW pure water, continuous gavage 4 weeks.
3.3, mice delayed allergy test (foot sole of the foot thickness increase method) (I criticizes animal)
The 4th day immune animal before off-test, by 2% (v/v) sheep red blood cell (SRBC) lumbar injection 0.2ml sensitized animal, after 5 days
Measuring left back sufficient sole of the foot portion thickness, then subcutaneous injection 20% (v/v) sheep red blood cell (SRBC) (20 every Mus of μ l/) at this, after injection, 24 is little
Time measure left back sufficient sole of the foot portion thickness three times, obtain meansigma methods.
3.4, the mouse spleen lymphocyte conversion test (mtt assay) (ii criticizes animal) of ConA induction
Prepared by splenocyte suspension: aseptic take spleen, is placed in the little plate filling appropriate aseptic Hank ' s liquid, with embedding son gently by spleen
Tear up, make individual cells suspension.Filtering through 200 eye mesh screens, Hank ' s liquid is washed 3 times, is centrifuged 10min (1000r/ every time
min).Then, by cell suspension in the complete culture solution of 2ml, CASY is used®DT cell counter counting splenocyte, adjusts thin
Born of the same parents' concentration is 3xl06Individual/ml.
Lymphproliferation response: cell suspension point holes added in 24 well culture plates, every hole lml, a hole adds 75 μ l
(being equivalent to 7.5 (μ g/ml), 5%CO, as comparison, is put in another hole to ConA liquid2, 37 ° of C cultivate 72h.Cultivation terminates first 4 hours, often
Hole sucks supernatant 0.7 ml, adds 0.7 ml serum-free RPMI RPMI-1640, is simultaneously introduced MTT
(5mg/ml) 50 μ l/ hole, continues to cultivate 4h.After cultivation terminates, every hole adds lml acid isopropyl alcohol, piping and druming mixing, makes
Purple crystal dissolves, and measures optical density value at microplate reader 570nm.
3.5, mice serum hemolysin titer determination (half hemolysis value method) (I criticizes animal)
The 4th day immune animal before off-test, the sheep red blood cell (SRBC) 0.2ml of every lumbar injection 2%, extracts eyeball and adopts after 5 days
Blood, separates serum standby.Hemolytic reaction: with SA buffer by serum-dilution 100 times, the serum lml after dilution is put in test tube,
It is sequentially added into 10% SRBC0.5ml, complement lml (pressing 1:8 dilution with SA liquid), separately sets the control tube of not increase serum；Put 37 ° of C
30min in incubator, ice bath terminates reaction, centrifugal (2000r/ min) l0min, takes supernatant 1ml, add Dou Shi reagent 3ml, with
Time take 10% SRBC0.25ml and add Dou Shi reagent to 4ml, fully mix；After placing 10 min, measure each at 540nm respectively
Pipe optical density value.
3.6, mouse boosting cell antibody tormation test (ii criticizes animal)
Immune animal: take the Sanguis caprae seu ovis of de-fiber, with brine 3 times, the most centrifugal (2000r/min) 10min, hematocrit
SRBC normal saline is made into the cell suspension of 2% (v/v), every Mus lumbar injection 0.2ml.
Prepared by splenocyte suspension: put to death de-white for the mice cervical vertebra after SRBC immunity 4 days, take out spleen, be placed on and fill
In the little plate of Hank ' s liquid, grind spleen gently, make cell suspension, filter through 200 eye mesh screens, centrifugal (l000r/
Min) l0min, washes 2 times with Hank ' s liquid, finally by cell suspension in 5ml RPMI1640 culture fluid, uses CASY®DT is thin
Born of the same parents' calculating instrument counting splenocyte, and cell concentration is adjusted to 5xl06Individual/ml.
The mensuration of plaque: after the culture medium heating for dissolving of top layer, puts 45-50 ° of C water bath heat preservation, with equivalent pH7.2-7.4,
Hank ' the s liquid mixing of 2 times of concentration, subpackage small test tube, often pipe 0.5ml, then (v/v uses SA to add 50 μ l l0%SRBC in pipe
Buffer), 25 μ l splenocyte suspensions, mix rapidly, be poured on the slide of own brush agarose thin layer, do parallel plate, treat
After agar solidification, slide level is buckled and is placed on horse, put into and CO2 gas incubator is hatched 1-1.5h, then delay with SA
The complement (1:8) rushing liquid dilution joins in slide frame M groove, after continuing incubation 1-1.5h, counts hemolysis plaque number.
3.7, mice carbonic clearance test (ii I criticizes animal)
The india ink that last dilutes with 1:4 after being administered, by every Mus 10g body weight 0.1ml tail vein injection, timing immediately, interval
2, within 10 minutes, take blood 20 μ l from angular vein clump respectively, add 2ml Na2CO3In solution, with spectrophotometer in 600nm wavelength
Place surveys OD value, uses Na2CO3Solution does blank, puts to death mice, takes liver, spleen is weighed, and calculates and gulps down index of sighing.
3.8, Turnover of Mouse Peritoneal Macrophages phagocytosis chicken red blood cell test (iv criticizes animal)
The activation of mouse macrophage: test first 4 days and inject 2% hematocrit sheeps blood erythrocyte 0.2ml to every mouse peritoneal.Use neck
Vertebra dislocation method puts to death mice, and lumbar injection adds Hank ' the s liquid 4ml of calf serum/only, rubs abdominal part gently 20 times, with fully
Wash out peritoneal macrophage, then stomach wall is cut off an osculum, draw abdominal cavity washing liquid 2ml in test tube with glue head straw.With
Lml sample injector is drawn abdominal cavity washing liquid 0.5ml and is added in the test tube filling 0.5ml 1% chicken red blood cells suspension, mixing.With injection
0.5ml mixed liquor drawn by device, adds in the agar circle of slide.The placement 37 ° of C in case that present a gift to a bereaved family hatch 15-20 minute.After hatching end fast
Non-attached cell is washed out by speed normal saline, fixes 1min, Giemsa liquid and contaminate 15 minutes in methanol solution.Rush with distilled water
Wash clean, dries, with 40x microscopic counting phagocytic rate and phagocytic index.Phagocytic rate is in every 100 macrophages, swallows chicken
Percentage rate shared by erythrocytic macrophage: phagocytic index is the number of average each macrophage phagocytic chicken red blood cell.
3.9, NK cytoactive detection (LDH method) (ii criticizes animal)
The preparation (effector lymphocyte) of splenocyte suspension: aseptic take spleen, is placed in the little plate filling appropriate aseptic Hank ' s liquid, uses
Spleen is torn up by tweezers gently, makes single cell suspension.Filtering through 200 eye mesh screens, Hank ' s liquid is washed 3 times, is centrifuged l0min every time
(1000r/min).Then, by cell suspension in the complete culture solution of 2ml, CASY is used®DT cell counter counting splenocyte,
Finally adjusting cell concentration with RPMI1640 complete culture solution is 2xl07Individual/ml.
NK cytoactive detects: taking concentration is 4x105The YAC-1 target cell of individual/ml and each 100 μ l of effector lymphocyte (effect target
Than 50:1), add U-shaped 96 well culture plates；Target cell Spontaneous release hole adds target cell and each 100 μ l of culture fluid, and target cell is maximum
Release aperture adds target cell and each 100 μ l of 1%NP40, above-mentioned every is all provided with three multiple holes, in 37 ° of C, 5%CO2Incubator is cultivated
Then 96 well culture plates are centrifuged 5min with 1500 r/min by 4h, and every hole is drawn in 96 well culture plates at the bottom of supernatant 100 μ l horizontalization,
Being simultaneously introduced LDH matrix liquid 100 μ l, react 3min, every hole adds lmol/1 HC130 μ l, measures light at microplate reader 490nm
Density value.
4, result judges:
4.1, enhancing immunity function judges: at cellular immune function, humoral immune function, monokaryon one macrophage function, NK
Any two aspect results of four aspects of cytoactive are positive, can determine that this given the test agent enhancing immunity function.
4.2, cellular immune function result judges: two result of the tests in cellular immune function assay project are sun
Property, or two dosage group results of any one test are positive, can determine that cellular immune function assay result is positive.
4.3, humoral immune function result judges: two result of the tests in humoral immune function mensuration project are sun
Property, or two dosage group results of any one test are positive, can determine that humoral immune function measurement result is positive.
4.4, monokaryon one macrophage function result judges: two examinations in monokaryon one macrophage function mensuration project
Test result and be the positive, or two dosage group results of any one test are positive, can determine that monokaryon one macrophage function result
Positive.
4.5, NK cytoactive result judges: more than one dosage group result of NK cytoactive detection test is positive, can
Judge that NK cytoactive result is positive.
5, result of the test:
5.1, the compound vitamin amino acids oral-liquor impact on Mouse Weight: serum hemolysin is shown in delayed allergy group
Table 4, lymphocyte transformation, NK determination of activity, antibody tormation group be shown in Table 2, and carbonic clearance test group is shown in Table 6, swallows chicken red blood cell group
It is shown in Table 7.Each dosage group each phase body weight weight ratio in period corresponding to matched group relatively, difference there are no significant meaning, show compound dimension
The body weight of mice is grown and has no significant effect by raw element amino acids oral-liquor.
Table 4 compound vitamin amino acids oral-liquor on the impact of Mouse Weight (I criticizes animal, n=10,± S)
Table 5 compound vitamin amino acids oral-liquor on the impact of Mouse Weight (ii criticizes animal, n=10,± S)
Table 6 compound vitamin amino acids oral-liquor on the impact of Mouse Weight (ii I criticizes animal, n=10,± S)
Table 7 compound vitamin amino acids oral-liquor on the impact of Mouse Weight (iv criticizes animal, n=10,± S)
5.2, compound vitamin amino acids oral-liquor is on mouse spleen weight and the impact of thymic weight: each dosage group internal organs/body
Anharmonic ratio value compares with matched group, difference there are no significant meaning (being shown in Table 8).Show that compound vitamin amino acids oral-liquor is to mice
Spleen weight and thymic weight have no significant effect.
Table 8 compound vitamin amino acids oral-liquor on mouse thymus, spleen weight impact (n=10,± S)
5.3, the compound vitamin amino acids oral-liquor impact on the delayed allergy of mice: the high dose group foot sole of the foot thickens value
Higher than matched group, difference has significant (being shown in Table 9).Show that the delayed of mice is become by compound vitamin amino acids oral-liquor
State reaction test result is positive.
Table 9 compound vitamin amino acids oral-liquor on the impact of mice delayed allergy (±S)
The impact of the mouse spleen lymphocyte conversion reaction that ConA is induced by 5.4 compound vitamin amino acids oral-liquors: each dosage
Group optical density difference compares with matched group, difference there are no significant meaning (being shown in Table 10).Show that compound vitamin aminoacid is administered orally
The spleen lymph conversion test result of liquid is negative.
Table 10 compound vitamin amino acids oral-liquor on the impact of mouse spleen lymphocyte conversion reaction (±S)
The 5.5 compound vitamin amino acids oral-liquors impact on animal subject serum hemolysin: the half of high dose group is molten
Blood value is higher than matched group, and difference has significant (being shown in Table 11).Show that Multiritamin amino acid oral liquid is molten to animal subject serum
Sanguinin level determination result of the test is positive.
Table 11 compound vitamin amino acids oral-liquor on the impact of mice serum hemolysin level (±S)
5.6, the compound vitamin amino acids oral-liquor impact on animal subject splenocyte antibody tormation level: the spleen of high dose group
Cell antibody generates level and is higher than matched group, and difference has significant (being shown in Table 12).Show that compound vitamin aminoacid is administered orally
Liquid is positive to animal subject splenocyte antibody tormation level determination result.
Table 12 compound vitamin amino acids oral-liquor on the impact of mouse boosting cell antibody tormation level (±S)
5.7, the compound vitamin amino acids oral-liquor impact on mice carbonic clearance phagocytic function: the phagocytosis of each dosage group carbonic clearance refers to
Number compares with matched group, difference there are no significant meaning (being shown in Table 13).Show the carbonic clearance of compound vitamin amino acids oral-liquor
For feminine gender.
Table 13 compound vitamin amino acids oral-liquor on the impact of mice carbonic clearance phagocytic function (±S)
The 5.8 compound vitamin amino acids oral-liquors impact on Turnover of Mouse Peritoneal Macrophages phagocytosis chicken red blood cell phagocytic function: each
Dosage group phagocytic percentage conversion value and phagocytic index index compare with matched group, difference there are no significant meaning (being shown in Table 14).
Show that the Turnover of Mouse Peritoneal Macrophages phagocytosis chicken red blood cell result of the test of compound vitamin amino acids oral-liquor is for negative.
The table 14 compound vitamin amino acids oral-liquor shadow to Turnover of Mouse Peritoneal Macrophages phagocytosis chicken red blood cell phagocytic function
Ring (n=10, ± S)
The 5.9 compound vitamin amino acids oral-liquors impact on animal subject NK cytoactive: the NK cytoactive of high dose group
Conversion value is higher than matched group, and difference has significant (being shown in Table 15).Show that compound vitamin amino acids oral-liquor is to tested dynamic
Thing NK cell activity assays result is positive.
Table 15 compound vitamin amino acids oral-liquor on NK cells in mice activity impact (n=10,±S)
In sum: SPF level Kunming kind healthy mice is given every day 2.08,4.17, answering of concentrating of 12.50ml/kg BW2 times
Closing vitamin amino acids oral-liquor, result shows: serum hemolysin testing result and spleen after sheep red blood cell (SRBC) immunization of animal subjects
It is positive that cell antibody generates result of the test, and given the test agent has enhancing body fluid immunity function；Animal subject NK cytoactive
The test positive, given the test agent has enhancing NK cytoactive effect.The mice delayed allergy examination of sheep red blood cell (SRBC) induction
Test high dose group positive, the mouse spleen lymphocyte proliferation negative of ConA induction；Animal subject carbonic clearance test the moon
Property, animal subject macrophage phagocytic chicken red blood cell negative, given the test agent does not have enhancing monokaryon-huge] according to " health care
Food test and assessment technique specification " enhancing immunity functional evaluation standard；Take liquid and there is enhancing immunity function.
Test example four, the test of alleviating physical fatigue of compound vitamin amino acids oral-liquor
1, subjects: choosing 160 SPF level Kunming female white mice of kind, 68 week old, body weight is 18g-22g, by Guangdong Province
Medical experiment animal center provides.
2, test material: the compound vitamin amino acids oral-liquor of embodiment 4, measures blood urea nitrogen enzyme process test kit, by
Beijing Jiuqiang Biotechnology Co., Ltd. provides；Measure lactic acid LACTATE PAP enzyme process test kit, by Beijing Li Demansheng
Changing technology company to provide, other agents useful for same are AR level, buy from biochemical reagents shop, Guangzhou.
3, test method:
Experimental animal is randomly divided into 4 batches after adapting to 3 days in laboratory conditions, every batch of according to dosage design is divided into 4 groups, the most right
According to group, low dose group, middle dosage group and high dose group, often 10 animals of group.The dosage of basic, normal, high three dosage groups is for implementing
Example 4 preparation the 4.17 of compound vitamin amino acids oral-liquor, 8.33,25.00ml/kg BW, this test employing 2 times of concentrated solutions
Testing, conversion post dose is 2.08,4.17,12.50 ml/kg BW, is equivalent to the 5 of human body recommended amounts, 10,30 times, separately
If matched group.Successive administration 30 days, measures under mice burden swimming time, urea nitrogen content, blood lactase acid curve during off-test
Area and hepatic glycogen content.
3.1, Loaned swimming test: giving 2 times and concentrate compound vitamin amino acids oral-liquor 30 days, last gives tested
After thing 30min, the mice of root of the tail portion load 5% body weight sheet lead is placed in depth of water 30cm, the swimming trunk middle reaches of 25 ± 0.5 ° of C of water temperature
Swimming, mice starts to dead time, i.e. mice burden swimming time record from swimming.
3.2, serum urea nitrogen determination: after last gives 2 times of concentration compound vitamin amino acids oral-liquor 30min, each group
Without the mice that bears a heavy burden respectively at 30 ° of C water went swimming 90min of water temperature, adopting eyeball blood after having a rest 60 minutes, it is little that 4 ° of C refrigerators place 3
Serum is separated, with enzyme process kit measurement blood urea nitrogen time after.
3.3, Serum lactic acid content measures: after last gives 2 times of concentration compound vitamin amino acids oral-liquor 30min, and first
Secondary adopt eyeball blood after be i.e. put in 30 ° of C of water temperature and swim l0min, for the second time eyeball blood, then stop quiet 20min, third time is adopted
Eyeball blood, the lactic acid of 0min, 20min after measuring the front lactic acid of swimming respectively with LACTATE PAP test kit and swim, according to public affairs
Formula calculates three time point lactic acid area under curve=5x (blood lactase acid value+2 x swimming of 0min after blood lactase acid value+3x swimming before swimming
The blood lactase acid value of rear rest 20min)
3.4, hepatic glycogen measures: use anthrone method.After last gives 2 times of concentration compound vitamin amino acids oral-liquor 30min, accurate
Really weighing 50mg liver, add 4ml 5%TCA liquid, often pipe homogenate lmin, is centrifuged 15min with 3000 turns/min, takes supernatant
0.5ml, adds 95% ethanol 2ml, fully mixes, 37 DEG C of water-bath 3h, dissolves glycogen with lml distilled water, and vibration is until glycogen is complete
After dissolving, 5ml anthrone reagent is added each pipe, immerse boiling water 15min, by VERSA microplate reader (wavelength 620nm) colorimetric after cooling
Measure.Hepatic glycogen content is calculated by formula.
4, result judges: swimming with a load attached to the body experimental result is positive, and blood lactase acid, serum urea nitrogen, three biochemistry of hepatic glycogen refer to
Mark is appointed binomial index positive, can determine that this given the test agent has the effect of function of physical fatigue alleviation.
5, result of the test:
The 5.1 compound vitamin amino acids oral-liquors impact on the mice burden swimming time: from table 16, each dosage group mice
Walking weight load compares prolongation with negative control group, difference statistically significant (P≤0.05), shows that mice burden swimming tries
Test result positive.
Table 16 compound vitamin amino acids oral-liquor on the impact of mice burden swimming time (±S)
5.2 compound vitamin amino acids oral-liquors are on the impact of serum urea nitrogen content after mouse movement: from table 17, low dose
After amount group mouse movement, serum urea nitrogen content reduces, and compares with negative control group, difference statistically significant (P≤0.01),
After showing mouse movement, serum urea nitrogen result of the test is positive.
Table 17 compound vitamin amino acids oral-liquor on after mouse movement serum urea nitrogen content impact (±S)
The impact of 5.3 compound vitamin amino acids oral-liquor Serum lactic acid contents forward and backward on mouse movement:
From table 18, table 19, the blood lactase acid area under curve of each dosage group mice compares with negative control group, and difference is all without system
Meter learns meaning, (P > 0.05), shows that Mouse Blood lactic acid content result of the test is negative.
The impact of table 18 compound vitamin amino acids oral-liquor Serum lactic acid content forward and backward on mouse movement (±S)
Table 19 compound vitamin amino acids oral-liquor on the impact of Mouse Blood lactic acid area under curve (±S)
5.4, the compound vitamin amino acids oral-liquor impact on Mouse Liver glycogen: from table 20, the liver of each dosage group mice
Glycogen content increases, and compares with negative control group, and difference is statistically significant, shows that Mouse Liver Glycogen assay result is positive.
Table 20 compound vitamin amino acids oral-liquor on the impact of Mouse Liver glycogen (±S)
The compound vitamin amino acids oral-liquor impact on Mouse Weight: from table 16,17,19,20, each dosage treated animal
Starting weight and eventually weight compare with negative control group, and the equal not statistically significant of difference (P > 0.05) shows that given the test agent is to test mice
Body weight increase have no significant effect.SPF level Kunming mouse per os every day is given dosage be 2.08,4.17,12.50ml/
2 times of concentration compound vitamin amino acids oral-liquors of kgBW, according to Ministry of Public Health " health food inspection and assessment technique specification "
(version in 2003) function of physical fatigue alleviation standard judges, submitted sample Multiritamin amino acid oral liquid has alleviating physical fatigue
Function.
The impact of idiopathic pulmonary fibrosis is tested by test example five, compound vitamin amino acids oral-liquor
1, subjects: choosing healthy male SD rat 50, body weight is 260-280g, Zhongshan University's Experimental Animal Center carry
Supply.
2, test material: embodiment 4 and the compound vitamin amino acids oral-liquor of comparative example 3 preparation, pirfenidone capsule,
It is purchased from Beijing Kangdini Pharmaceutical Co., Ltd., traditional Chinese medicines quasi-word H20133376.
3, idiopathic pulmonary fibrosis Animal Model:
From 50 rats, random choose 10 is only used as control rats, and remaining rats by intraperitoneal injection 3% concentration is 30mg/kg
Pentobarbital sodium, fixing Mus platform of lying on the back after anesthesia, routine disinfection drape after cervical region preserved skin, cut after skin successively blunt separation
Expose trachea, thrust tracheal strips with the syringe diagonal of 1mL, fast injection bleomycin solution 0.2-0.3ml in lung, immediately
Hold up Mus plate, after the 2min that rolls, sterilization skin closure wound again.
6, test method:
Successful for modeling 40 rats are randomly divided into model group, pirfenidone group, test 1 group and test 2 groups, respectively organize dosage
As follows:
Matched group: the isopyknic normal saline of gavage；
Model group: the isopyknic normal saline of gavage；
Pirfenidone group: the pirfenidone of gavage 10mg/kg；
Test 1 group: the compound vitamin amino acids oral-liquor of embodiment 4 preparation of gavage 10ml/kg；
Test 2 groups: the compound vitamin amino acids oral-liquor of comparative example 3 preparation of gavage 10ml/kg.
During test, rat freely drinks water, and takes food (standard diet).Measure rat body weight once weekly.In on-test
The 4th week execution rat after administration.Use femoral artery depletion method to put to death rat, after pentobarbital sodium anesthesia, rat is lain on the back solid
On Mus platform, open breast and appear cardiopulmonary, repeatedly clean with normal saline after taking off lungs, weigh in electronic balance and lung
Weight, calculates paragonimus cyst (lung weight/body weight × 100%), uses the Serum Laminin (LN) of test kit detection rat
Content.Then, use 4% formaldehyde to fix right upper lung, lower-left lung, conventional dehydration embedding, make 5 μm thickness paraffin sections, in case HE
Dyeing.
The pathology semi-quantitative analysis of idiopathic pulmonary fibrosis, the judgment criteria of alveolitis and pulmonary fibrosis degree is as follows:
(1) alveolitis classification:
0 grade: without alveolitis；
1 grade: slight alveolitis, extent of disease is confined to full lung less than 20%；
2 grades: moderate alveolitis, extent of disease accounts for full lung 20%-50%；
3 grades: Diffuse alveolar is scorching, extent of disease is more than 50%.
(2) interstitial pulmonary fibrosis classification:
0 grade: without interstitial pulmonary fibrosis；
1 grade: slight interstitial pulmonary fibrosis, extent of disease is confined to full lung less than 20%；
2 grades: moderate interstitial pulmonary fibrosis, extent of disease accounts for full lung 20%-50%；
3 grades: severe interstitial pulmonary fibrosis, extent of disease be more than 50%, fusion of pulmonary alveoli, pulmonary parenchyma structure disturbance.
Utilize microimage analysing system, pathological section is carried out alveolitis and fibrosis is measured automatically, by lung group
Knit HE dyeing pathological section to be divided into three below region and be analyzed:
Without dye district: for alveolar space occupied area；
Shen Ran district: for nucleus occupied area；
Understain district: for interstitial lung fibrous connective tissue occupied area.
The degree of alveolitis and pulmonary fibrosis can be determined by the difference of three above region occupied area.During alveolitis
Interstitial lung inflammatory cell infiltration increases, and showing as Shen Ran district area increases, and during interstitial pulmonary fibrosis, alveolar mostly subsides or disappears
Losing, there are a large amount of collagen fiber in interstitial, shows as reducing without dye district area, and understain district area increases.Cell is represented with Shen Ran district
Core occupied area, i.e. alveolar inflammation area, understain district represents fibrous connective tissue and collagen fiber occupied area, represents without dye district
Alveolar space area.Being placed in by pathological section under image analyzer microscope, under the 10x visual field, every section is by left-to-right, by upper
Choose 10 visuals field under to successively and carry out graphical analysis.
5, result of the test:
5.1, compound vitamin amino acids oral-liquor is on the impact of idiopathic pulmonary fibrosis rat model paragonimus cyst and LN content such as
Shown in table 4.
Table 21 compound vitamin amino acids oral-liquor is to idiopathic pulmonary fibrosis rat model paragonimus cyst and the shadow of LN content
Ring
As shown in Table 21, compared with model group, pirfenidone group and test 1 group all can significantly reduce idiopathic pulmonary fibrosis
The paragonimus cyst of model, and the reducing effect testing 1 group is close with pirfenidone group, and meanwhile, testing 1 group can also significantly reduce
The LN content of idiopathic pulmonary fibrosis model, illustrates that the compound vitamin amino acids oral-liquor that the present invention provides is fine to idiopathic lung
Dimensionization has significant improvement result.
5.2, the compound vitamin amino acids oral-liquor impact on pathologic:
Compared with matched group, model group rats presents severe alveolitis, and there is more hemorrhagic focus local, and alveolar septum is broadening, and inflammatory is thin
Born of the same parents infiltrate, and macrophage activation is obvious: volume increases, and intracellular containing a large amount of granules, major part macrophage is that foam sample changes
Become；The fibroblast that lamellar assembles activation is the most adjacent, and alveolar septum and areas of inflammation are shown in the collagen fiber of lamellar hypertrophy, fiber
Change degree substantially increases.Compared with model group, pirfenidone group and test 1 group all can significantly improve idiopathic pulmonary fibrosis mould
The alveolitis of type, macrophage foam cell formation sample change, fibrocyte activation and the symptom such as collagen fiber hyperplasia, and test 2 groups change
Kind DeGrain, illustrates that idiopathic pulmonary fibrosis is had significantly by the compound vitamin amino acids oral-liquor that the present invention provides
Improvement result.
Claims (10)
1. a compound vitamin amino acids oral-liquor, it is characterised in that include following component and parts by weight thereof:
Isoleucine 5.5-8.5 part, threonine 4.5-7 part, valine 4.5-7 part, aspartic acid 4.5-7 part, arginine hydrochloride
3-4.5 part, lysine hydrochloride 3-4.5 part, phenylalanine-3,4-quinone-4.5 parts, methionine 3-4.5 part, leucine 1.5-2.5 part, color ammonia
Acid 0.46-0.8 part, nicotiamide 0.32-0.48 part, vitamin B10.07-0.12 part, vitamin B20.032-0.048 part, dimension
Raw element B60.032-0.048 part, water adds to 1000 parts.
2. compound vitamin amino acids oral-liquor as claimed in claim 1, it is characterised in that include following component and weight thereof
Number:
Isoleucine 7.1 parts, threonine 5.9 parts, valine 5.87 parts, aspartic acid 5.7 parts, arginine hydrochloride 5 parts, hydrochloric acid rely
Propylhomoserin 4.62 parts, phenylalanine-3,4-quinone .74 part, methionine 3.7 parts, leucine 1.86 parts, tryptophan 0.66, nicotiamide 0.4 part, dimension
Raw element B10.1 part, vitamin B20.04 part, vitamin B60.04 part, water adds to 1000 parts.
3. compound vitamin amino acids oral-liquor as claimed in claim 1 or 2, it is characterised in that described compound vitamin ammonia
Base acid oral liquid also comprises the following components and parts by weight:
Stabilizer 2-8 part, erythritol 1-4 part, assorted fruital essence 0.5-1.5 part, cyclamate 0.1-1 part, raspberry essence 0.1-1
Part, sucralose 0.1-1 part, acesulfame potassium 0.1-0.5 part, Herba Menthae 0.001-0.05 part and neotame 0.001-0.05 part.
4. compound vitamin amino acids oral-liquor as claimed in claim 3, it is characterised in that described compound vitamin aminoacid
Oral liquid includes following component and parts by weight thereof:
Isoleucine 7.1 parts, threonine 5.9 parts, valine 5.87 parts, aspartic acid 5.7 parts, arginine hydrochloride 5 parts, hydrochloric acid rely
Propylhomoserin 4.62 parts, phenylalanine-3,4-quinone .74 part, methionine 3.7 parts, leucine 1.86 parts, tryptophan 0.66, nicotiamide 0.4 part, dimension
Raw element B10.1 part, vitamin B20.04 part, vitamin B60.04 part, stabilizer 5.5 parts, erythritol 2.48 parts, assorted fruital
Essence 0.96 part, cyclamate 0.48 part, raspberry essence 0.24 part, sucralose 0.225 part, acesulfame potassium 0.172 part, Herba Menthae
0.018 part, neotame 0.01 part, water adds to 1000 parts.
5. compound vitamin amino acids oral-liquor as claimed in claim 3, it is characterised in that described stabilizer is by citric acid
Sodium, sodium D-isoascorbate and xanthan gum form by weight 0.8-1.5:0.006-0.015:0.6-1.
6. compound vitamin amino acids oral-liquor as claimed in claim 5, it is characterised in that described stabilizer is by citric acid
Sodium, sodium D-isoascorbate and xanthan gum form by weight 1:0.01:0.8.
7. the preparation method of a compound vitamin amino acids oral-liquor as claimed in claim 1 or 2, it is characterised in that bag
Include following steps:
S1 takes the water ebuillition of heated 10-20min of half amount, is cooled to 70-80 DEG C, add isoleucine, threonine, valine,
Aspartic acid, arginine hydrochloride, lysine hydrochloride, phenylalanine, methionine, leucine, tryptophan, nicotiamide, vitamin
B1, vitamin B2And vitamin B6, stirring, to being completely dissolved, obtains mixed liquor I；
The mixed liquor I that step S1 is obtained by S2 is cooled to 30-40 DEG C, adds remaining water, obtains mixed liquor I I；
Mixed liquor I I that step S2 is obtained by S3 filters, embedding, and sterilizing 8-35min to obtain final product.
8. the preparation method of compound vitamin amino acids oral-liquor as claimed in claim 7, it is characterised in that described step S1
It is additionally added stabilizer, erythritol, cyclamate, sucralose, acesulfame potassium, Herba Menthae and neotame；Add after the cooling of described step S2
Assorted fruital essence and raspberry essence.
9. the preparation method of compound vitamin amino acids oral-liquor as claimed in claim 7, it is characterised in that described step S3
In sterilising temp be 110-121 DEG C.
10. the compound vitamin amino acids oral-liquor as described in claim 1-9 is arbitrary is fine at preparation auxiliary treatment idiopathic lung
Application in dimensionization health product.
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| CN106174392A (en) * | 2016-07-16 | 2016-12-07 | 山东阜丰发酵有限公司 | A kind of built amino-acid being applicable to compound seasoner and preparation method thereof |
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| CN113209013A (en) * | 2021-06-24 | 2021-08-06 | 新疆特丰药业股份有限公司 | Midazolam liquid preparation and preparation method and application thereof |
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|---|---|
| CN105708829B (en) | 2017-04-12 |
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