CN106176756A - The lysine five comprising chiral photo-isomerisation compound ties up medical composition and its use - Google Patents
The lysine five comprising chiral photo-isomerisation compound ties up medical composition and its use Download PDFInfo
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- CN106176756A CN106176756A CN201510217486.9A CN201510217486A CN106176756A CN 106176756 A CN106176756 A CN 106176756A CN 201510217486 A CN201510217486 A CN 201510217486A CN 106176756 A CN106176756 A CN 106176756A
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Abstract
The present invention provides the application in prevention or treatment people and the five kinds of vitamin comprising chiral photo-isomerisation compound of mammal 1B shortage, retarded growth etc. and the health food of lysine compositions or medicine so that product has more new adaptation population or more preferable specific aim and more preferable clinical safety etc. on Clinical practice.
Description
Technical field
The present invention relates to pharmaceutical technology field, be specifically to provide prevention or treatment promotes normal growth to grow or L-relies
The anacid patient of ammonia supplement 1B or metabolic acidosis, hyperchloremia but need to mend comprising of lysine etc.
The lysine five of chiral photo-isomerisation compound ties up pharmaceutical composition or the pharmaceutical composition of five dimension lysines and preparation thereof and use
On the way.
Background technology
Lysine belongs to basic amino acid, has DL-Lys, D-Lys, three kinds of primitive forms of 1B, and L-relies
Propylhomoserin is one of necessary 8 kinds of aminoacid of human body, and 1B provides structural constituent for synthetic carnitine, and carnitine can promote carefully
The synthesis of fatty acid in born of the same parents.Particularly in childhood development phase, after being ill convalescent period, gestation lactication phase, to 1B
Requirement is higher.Owing to content is relatively low in the food such as rice, Semen Maydis, easily cause human body and lack, be referred to as " first
Lack amino acid ".
1B shortage can cause dysplasia, inappetence, lose weight, negative nitrogen balance, hypoproteinemia,
Hypoplasia of tooth, anemia, enzymatic activity decline and other physiological function obstacle.1B is improved intelligence, promotion
Growth, health invigorating；Appetite stimulator, improve malnutrition situation；Improve insomnia, improve memory；Help
Produce antibody, hormone and enzyme, improve immunity, increase hematochrome；The absorption of calcium, treatment is helped to prevent sclerotin
Osteoporosis and rickets；Help nervous tissue to repair, promote nervous cell regenerating, improve central nervous tissue function
Effect.Lysine can improve blood-brain barrier permeability, contributes to medicine and enters in brain cell, and clinical being used as treats cranium brain
Wound, chronic cerebral tissue ischemia, the cerebral protective agent of ischemic disease, or the auxiliary of other encephalopathys is treated, it is also possible to
In 1B lack cause children's's inappetence, malnutrition and cerebral dysgenesis (Liu Xiaolan, etc., L-relies ammonia
The medical applications new development of acid, the modern internal medicine magazine of China, 2006 (3) 8:923-924).
Vitamin B1It is necessary to human energy metabolism and carbohydrate metabolism, promotes tricarboxylic acid cycle in vivo, produce ATP,
Also it is to maintain heart, necessary to nerve and digestive system normal function.
Vitamin B2Flavin mononucleotide (FMN) and flavin dinucleotide can be converted into, be the important coenzyme of Tissue respiration, and
Vitamin B can be activated6, be body fat and glycometabolic required material, participate in internal many redox reaction and sugar,
Protein and the metabolism of fat, maintain emmetropia visual performance.
Vitamin B6Generate through enzyme effect with ATP in vivo and there is pyridoxal 5-phosphate and the phosphopyridoxamine of physiologically active,
Also be used as arteriosclerosis, bald head, hypercholesterolemia, cystitis, hypoglycemia, mental disorder, pellagra and
The auxiliary treatment of his muscular dystrophy etc..
D-VB5 is the precursor of coenzyme A, participates in protein, fat, sugar metabolism in vivo.Health each
Individual cell is required for pantothenic acid, cannot be otherwise energy by sugar or adipose conversion, also cannot utilize para-amino benzoic acid and gallbladder
Alkali.When lacking pantothenic acid, adrenal gland is particularly easy to impaired, enlargement or hemorrhage, it is impossible to secretion cortisone and other hormones.
Under any pressure, such as disease, injury, drug side effect, scald, surgical operation, depressed etc., need
When wanting more hormone, the requirement of pantothenic acid is increased the most accordingly.Mammal and human body lack pantothenic acid can cause growth
Stop, losing weight, the symptom such as sudden death, skin, hair obstacle, nervous system disorders, hepatic insufficiency.
The order of severity that mouse lacks pantothenic acid and infected by antibacterial, is directly proportional to the time length lacked.When people are passed
The threat caught an illness, and when adrenal function is normal, tonsil, lymph gland etc. can reduce, only lack pantothenic acid and
His nutrient, causes adrenal gland failure, tonsil and lymph gland enlargement, just can viral infection disease.Pantothenic acid is to human body
There is very important protective effect to be also embodied in, prevent internal protein from being destroyed, prevent blood sugar concentration and blood pressure
Decline, it is to avoid the calcium loss etc. in skeleton.But, pantothenic acid is different due to its chiral isomer, has raceme and two kinds
Three kinds of different chemical entities of optical isomer, two kinds of i.e. dextroisomer D-VB5s of isomer and laevoisomer L-
Pantothenic acid, but only D-VB5 just has biological activity, and L-type, then entirely without biological activity, only has D-VB5 in raceme
Just there is biological activity (Wang Dong, etc., pantothenic acid and calcium pantothenate, veterinary drug feed additive, 1997,6,21-22).
At present, disclosed document reports the composite preparation (document: five dimension lysine particles, state of five dimension lysines
Family's standard WS-10001-(HD-0597)-2002), it is primarily to facilitate child, Children Normal growth promoter and old body
The nutritional supplementation of weak person.Oral.Less than 1 year old: 1 time on the one, one time 1 bag；More than 1 year old: 2 times on the one, once
1 bag.Boiled water is taken after mixing it with water.
But not yet there are open source literature report LYS L-lysine acetate or lysine acetate or lysine or L-
The compositions of five dimension lysines of lysine, also there is no the compositions of high-load in reported literature unit formulation or new height
The compositions etc. that weight is constituted.There is many deficiencies in the preparation of prior art, contains the D-of half in its lysine hydrochloride
Lysine and 1B, only 1B are the most easily absorbed by organisms utilization, have bigger value to human body,
And D-Lys is difficult to the utilization that is absorbed by the body；Although currently also open report title is defined to single optical isomer
L-lysine hydrochloride granule, but be only limitted to one-component and be administered.Additionally, five dimension lysine particle in prior art
Agent there is also the patient being not suitable for hyperchloremia, acidosis and renal insufficiency etc. in some cases, especially in advance
Unknown or take in the case of being difficult to know and may bring adverse consequences；And current preparation does not limit and uses L-
Lysine, this quality making preparation or nutrition or therapeutic value or be restricted and maybe can not be in Optimal State；Furthermore,
In the current compositions preparation when increasing a multiple dose unit, increase the D-Lys that half is difficult to be absorbed and used,
One unit dose is the biggest, and Time of Administration is the longest, wastes the biggest.This makes manufacturing, on taking convenience, transport and
There is also problem in packaging and maybe can not be suitable to the greatest extent clinical practice, be less useful for saving human resources and Resources for construction saving
Type is social, and this rough sledding is ignored the most always and improved, and unnecessary packaging also increases to environmental conservation
Plus-pressure, but there is not yet and breaks through old framework.[hyperchloremia or the list of references of the aspect such as hyperchloremia or acidosis:
Document 1, Li Zhaoquan, intracranial hematoma complicated by postoperative hypernatremia 12 example clinical analysis, practical sacred disease magazine, 2005
05 phase of year, p.44-45；Document 2, Zhang Xuejun, Chen Zhiqin, Li Hua, after cerebral hemorrhage, the clinic of Hypernatremia and Hyperchloremia is ground
Study carefully, apoplexy and sacred disease magazine, the 5th phase of volume 24 in 2007, p.609-611；Document 3, season hamming, 11
Example heavy type head-brain injury merging hyperglycemia, hypernatremia, hyperchloremia experiences on diagnosis and treatment, Jiangsu Clinical Medical Journals, 1998 the 2nd
Roll up the 6th phase, p.505,507；Document 4, Yin Peida, the pathogeny of distal renal tubular acidosis, foreign medical science is (interior
Science fascicle), phase nineteen eighty-two 12；Document 5, Zhang Yaoping, Lai Yonghong；Aninon gap analysis in department of pediatrics illness
With application, Guangzhou Medical College journal, phase nineteen ninety 03].
Summary of the invention
Involved in the present invention is to include that the lysine five of chiral photo-isomerisation compound ties up pharmaceutical composition or five dimension lysines
Pharmaceutical composition and preparation thereof and purposes, particularly relate to prevention or the LYS for the treatment of calcium deficiency or L-vinegar
Acid lysine or lysine acetate or lysine or 1B and the compositions of five kinds of vitamin and preparation thereof and purposes.
The compositions of the five dimension lysines of the present invention: principal agent component in the said composition of a unit dose or unit formulation
Weight or weight ratio be: LYS or its solvated compounds 45.0～220mg or L-lysine acetate or vinegar
Acid lysine or its solvated compounds 50.81～248.41mg or lysine or 1B or its solvated compounds
36.02～176.08mg, vitamin B1Or its solvated compounds 0.96～5.28mg, vitamin B2Or its solvent chemical combination
Thing 0.12～0.66mg, vitamin B6Or its solvated compounds 0.06～0.33mg, nicotiamide or its solvated compounds
2.12～10.56mg, D-VB5 calcium or D-VB5 calcium 2 hydrate 0.12～0.66mg；Wherein, each principal agent component
Calculated weight when solvated compounds is converted into corresponding solvent-free chemical combination, such as: L-lysine acetate or lysine acetate
Or lysine or 1B or vitamin B1Or vitamin B2Or vitamin B6Or nicotiamide or the solvent of D-VB5 calcium
Calculated weight when chemical combination is all converted into solvent free compound according to it, solvated compounds includes hydrate.
Further, the compositions of the five dimension lysines of the present invention: in the said composition of a unit dose or unit formulation
The weight of principal agent component or weight ratio be: LYS or its solvated compounds 45.0～220mg or L-acetic acid rely
Propylhomoserin or lysine acetate or its solvated compounds 50.81～248.41mg or lysine or 1B or its solvation
Compound 36.02～176.08mg, vitamin B1Or its solvated compounds 0.96～5.28mg, vitamin B2Or its solvent
Compound 0.12～0.66mg, vitamin B6Or its solvated compounds 0.06～0.33mg, nicotiamide or its solvent chemical combination
Thing 2.12～10.56mg, D-VB5 calcium or D-VB5 calcium 2 hydrate 0.12～0.66mg；And it is pharmaceutically acceptable
One or more adjuvants or carrier；Wherein, the solvated compounds of each principal agent component is converted into corresponding solvent free
Calculated weight during conjunction, such as: L-lysine acetate or lysine acetate or lysine or 1B or vitamin B1Or
Vitamin B2Or vitamin B6Or the solvent chemical combination of nicotiamide or D-VB5 calcium is all converted into solvent free compound according to it
Time calculated weight.
The compositions of the five dimension lysines of the present invention is more preferably: in the said composition of a unit dose or unit formulation
The weight ratio of principal agent component is: LYS or its solvated compounds 45.0～55mg or L-lysine acetate or vinegar
Acid lysine or its solvated compounds 50.81～62.10mg or lysine or 1B or its solvated compounds
36.02～44.02mg, vitamin B1Or its solvated compounds 0.96～1.44mg, vitamin B2Or its solvated compounds
0.12～0.18mg, vitamin B6Or its solvated compounds 0.06～0.09mg, nicotiamide or its solvated compounds 2.12～
2.88mg, D-VB5 calcium or D-VB5 calcium 2 hydrate 0.12～0.18mg；And pharmaceutically acceptable one or many
Plant adjuvant or carrier；Wherein, the solvated compounds of each principal agent component calculates when being converted into corresponding solvent free compound
Weight amount.
The compositions of the five dimension lysines of the present invention can be more preferably also: a unit dose or this combination of unit formulation
In thing, weight or the weight ratio of principal agent component are: LYS or its solvated compounds 50mg or L-acetic acid rely ammonia
Acid or its solvated compounds 56.458mg or 56.46mg56.5mgL-lysine or its solvated compounds 40.019mg or
40.02mg or 40mg, vitamin B1Or its solvated compounds 1.2mg, vitamin B2Or its solvated compounds 0.15
Mg, vitamin B6Or its solvated compounds 0.075mg, nicotiamide 2.4mg, D-VB5 calcium or D-VB5 calcium 2 water
Compound 0.15mg；And pharmaceutically acceptable one or more adjuvants or carrier；Wherein, each principal agent component is molten
Calculated weight when immunomodulator compounds is converted into corresponding solvent free compound.
The compositions of the five dimension lysines of the present invention can be more preferably also: the combination in a unit dose or unit formulation
Thing contains: LYS or its solvated compounds 100mg or L-lysine acetate or lysine acetate or it is molten
Immunomodulator compounds 112.915mg or 112.92mg or 112.9mg or 113mg or lysine or 1B or its solvent
Compound 80.0384mg or 80.038mg or 80.04mg or 80mg, vitamin B1Or its solvated compounds 2.4mg,
Vitamin B2Or its solvated compounds 0.30mg, vitamin B6Or its solvated compounds 0.15mg, nicotiamide 4.8mg,
D-VB5 calcium or D-VB5 calcium 2 hydrate 0.30mg；And pharmaceutically acceptable one or more adjuvants or carrier；
Wherein, the calculated weight when solvated compounds of each principal agent component is converted into corresponding solvent free compound.
The compositions of the five dimension lysines of the present invention can be more preferably also: the combination in a unit dose or unit formulation
Thing contains: LYS or its solvated compounds 150mg or L-lysine acetate or lysine acetate or it is molten
Immunomodulator compounds 169.3731mg or 169.373mg or 169.37mg or 169.4mg or 170mg or 169mg or bad ammonia
Acid or 1B or its solvated compounds 120.058mg or 120.06mg or 120mg or 120.1mg, vitamin
B1Or its solvated compounds 3.6mg, vitamin B2Or its solvated compounds 0.45mg, vitamin B6Or its solvent
Compound 0.225mg, nicotiamide 7.2mg, D-VB5 calcium or D-VB5 calcium 2 hydrate 0.45mg；And pharmaceutically
One or more adjuvants acceptable or carrier；Wherein, the solvated compounds of each principal agent component is converted into corresponding nothing
Calculated weight during solvated compounds.
The most each component is also possible at the 80-120% of the labelled amount of its principal agent constituent content, wherein, and each principal agent
The calculated weight when solvated compounds of component is converted into corresponding solvent free compound.
It is pointed out that the principal agent component or its contained in the compositions in a unit dose or a unit formulation
The weight ratio of principal agent component is: L-lysine acetate or lysine acetate or the 56.4577mg of its solvated compounds or
Between 56.458mg or 56.46mg or 56.5mg, or lysine or 1B or the 40.02mg of its solvated compounds
Or between 40.1mg or 40mg；Or L-lysine acetate or lysine acetate or the 112.915mg of its solvated compounds
Or between 112.92mg or 112.9mg or 113mg, or lysine or 80.04mg or 80.1mg of 1B
Or between 80mg；Or L-lysine acetate or lysine acetate or 225.831mg and 225.83mg of its solvated compounds
And between 225.83mg and 225.8mg and 226mg, or lysine or 1B or the 160.08 of its solvated compounds
Between mg and 160.1mg and 160mg and 161mg, it is equivalent or approximation effects equivalent in the present invention, because of
Significant digits are different and omitted or accepted or rejected；Principal agent or the significant digits of adjuvant in other compositions of the present invention
Choice mode or principle are also identical with this.
For the compositions in the pharmaceutical composition of the present invention, a unit dose or a unit formulation can contain
The LYS of high dose or L-lysine acetate or lysine acetate or lysine or 1B are (with anhydride
Calculate), or D-VB5 calcium or D-VB5 calcium 2 hydrate, this is according to different indications or crowd or all ages and classes
Depending on patient and aspect manufacture, transport or carry, reduce manufacturer's time expense, at double reduce packing charges or
Freight or taking convenience.The compositions of high unit dose is conducive to significantly reducing the consumption of adjuvant and improving production effect
Rate etc..
In the pharmaceutical composition of the present invention, the type of service of different component can be different, such as: LYS or L-
Lysine acetate or lysine acetate or lysine or 1B can be to use its crystalline hydrate (L-hydrochloric acid relies ammonia
Acid or L-lysine acetate or lysine acetate 1,2,3 hydrate etc.)；Vitamin B1, vitamin B2, vitamin
B6, nicotiamide, D-VB5 calcium or its crystalline hydrate, such as D-VB5 calcium 2 hydrate etc., if using its anhydride,
Its content or inventory can be converted accordingly according to the molecular weight of anhydride；This do not hinder other component use or
Do not use, when deployed, can carry out according to chemistry or pharmacy rule.
In the pharmaceutical composition of the present invention, the amount of each component or the pharmaceutically acceptable form of the difference (bag of each component
Include its salt or hydrate) can rationally change or adjust in the certain limit that present invention provide that, to form different combinations.
The purposes performance of the compositions of the five dimension lysines of the present invention is: said composition is individually or with pharmaceutically acceptable
Adjuvant, the application in preparing tablet, granule, capsule, powder, suspensoid, liquid preparation.
The LYS of the present invention or L-lysine acetate or lysine acetate or lysine or 1B and, dimension
Raw element B1, vitamin B2, vitamin B6, nicotiamide, D-VB5 calcium or the compositions of D-VB5 calcium 2 hydrate,
Also can add pharmaceutically acceptable adjuvant and be prepared as pharmaceutical preparation, including capsule, tablet (ordinary tablet, dispersible tablet,
Effervescent tablet, chewable tablet, oral cavity disintegration tablet etc.), granule, powder, suspensoid etc.；Its preparation method is for rely L-hydrochloric acid on ammonia
Acid or L-lysine acetate or lysine acetate or lysine or 1B and vitamin B1, vitamin B2, dimension raw
Element B6, nicotiamide, D-VB5 calcium or D-VB5 calcium 2 hydrate and pharmaceutically acceptable adjuvant be prepared from accordance with the law.
Wherein, pharmaceutically acceptable adjuvant includes filler, lactose, starch, microcrystalline Cellulose；Disintegrating agent such as hydroxypropyl forms sediment
Powder, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, sodium carboxymethyl cellulose, crospolyvinylpyrrolidone,
Guar natural gum, methylcellulose one or several；Lubricant such as magnesium stearate, zinc stearate, micropowder silica gel, cunning
Stone powder, Macrogol 2000-8000 one or several；Pharmaceutically acceptable correctives and or coloring agent (as Ah
This Ba Tian, cyclamate, saccharin sodium, sucralose, sweetleaf centautin, xylitol, sorbitol, xylose, lactose, sweet
Grass glucin, sucrose, citrus seed oil, oleum Citri sinensis, Fructus Citri Limoniae oil, Oleum menthae, linalool, menthol, curcumin, Monas cuspurpureus Went
Pigment, beet red, amaranth, Xylene Red, sunset yellow, Gardenia Yellow, chlorophyll, food coloring are red or edible
Pigment flavochrome, other sweeting agent or other essence or other pigment etc.) or pharmaceutically acceptable preservative or mildew-resistant
Agent or antibacterial (benzoic acid or its sodium or potassium salt, sorbic acid or its pharmaceutical salts, potassium sorbate or sodium sorbate, Ni Bo
Gold ester etc.) etc. in one or more.
The preparation method of solid preparation includes, supplementary material is crossed 60～200 mesh sieves respectively, and the L-hydrochloric acid after sieving relies
Propylhomoserin or L-lysine acetate or lysine acetate or lysine or 1B and vitamin B1, vitamin B2, dimension
Raw element B6, nicotiamide, D-VB5 calcium or D-VB5 calcium 2 hydrate and adjuvant mix homogeneously, carry out dry granulation or with
2-10% binding agent makes soft material, crosses 14～40 mesh sieves and pelletizes, and 40～80 DEG C are dried, and cross 14～40 mesh sieve granulate,
With disintegrating agent and magnesium stearate lubricant, zinc stearate, micropowder silica gel, Pulvis Talci, Macrogol 2000-8000
One or several (add pharmaceutically acceptable suspending agent or stabilizer when preparing suspensoid, as xanthan gum, tartaric acid,
Citric acid, tragakanta, gelatin, fructose, polyvinylpyrrolidone, methylcellulose, ethyl cellulose, carboxylic first
One or several mix homogeneously in base sodium cellulosate, sodium alginate, carboxymethyl starch sodium, pectin etc., survey granule and contain
Amount, in Filling bag), tabletting or encapsulated, pack, check, obtain finished product；
The LYS of one unit dose of the present invention or L-lysine acetate or 1B and D-VB5 calcium
Deng other three components compositions with as the compositions of other three components such as a unit dose lysine hydrochloride
Compare, medicine of the present invention can under similar circumstances or avoid using a half-value dose be difficult to be immediately used by the body D-hydrochloric acid and rely
Propylhomoserin, it means that in the case of same quality, the compositions of the present invention is possible not only to provide under square one more
The L-type lysine that the human body first of one multiple dose lacks, moreover it is possible to avoid or limit half being difficult to be absorbed by organisms utilization
D type isomer, can improve the efficiency etc. of transport calcium ion etc., increase D-VB5 calcium the most simultaneously.
Therefore, the present invention not only not only itself provides more L being available for human body utilization in the preparation of a unit dose
The lysine of configuration, increases D-VB5 calcium the most simultaneously, additionally aids and improve the absorption of calcium on the original basis and by body
Utilization rate, produce more preferable synergy.This also makes the patient for calcium deficiency, for sufferers of osteoporosis face,
In same situation, more preferable effect of supplemented calcium will be obtained.Being multiplied of L-type lysine in this unit dose,
Patient for cerebrovascular disease also has positive effect to a certain extent.
During production unit dosage particles, under square one, contribute to producing exponentially within the unit interval
Go out LYS in unit dose formulations or L-lysine acetate or the high preparation of 1B content or compositions,
Significantly decrease production cost and cost of transportation etc..
Therefore, for the compositions being relatively fixed dosage, for unit formulation or the unit of a new compositions
In dosage, the preparation containing further amounts of 1B is either for 1B or the child of calcium deficiency and adult, also
It is that positive meaning is had more for the preparation containing 1B, when manufacturing the compositions of high standard or high dose,
Save processing charges, packing charges and freight at double, also reduce environmental pollution and treatment of wastes produced, contribute to ring
The construction of the society of border friendly.
It was found that the principal agent combination of five dimension lysines of the different L-lysine acetate of the present invention or lysine acetate
The pH value of thing is close to physiology or more meaningful to acidosis patient.By following experiment, prior art is contrasted
Research.Under room temperature, about 20-25 DEG C, claim respectively to press lysine hydrochloride, vitamin B1, vitamin B2, vitamin
B6, nicotiamide, calcium pantothenate (respectively by weight 50:1.2:0.15:0.075:2.4:0.15 sample), take about 2.1
Gram in 50ml flask, add 20ml water for injection, be sufficiently stirred for or shake after within 20 minutes, placing, test its liquid
PH value, finds that its pH value is less than 6.0.For the compositions of the present invention, at room temperature, about 20-25 DEG C, respectively
Example 2, embodiment 3, embodiment 5, embodiment 7, embodiment 8, embodiment 13, embodiment 15, enforcement
Example 16, embodiment 17, embodiment 18, embodiment 19, the powder of four principal agent components of shown ratio of embodiment 21
About 2.1 grams of end is respectively placed in 50ml flask, adds 20ml water for injection, is sufficiently stirred for or shakes after within 20 minutes, placing,
Test the pH value of its liquid；Found that embodiment 3, embodiment 5, embodiment 7, embodiment 8, embodiment 13,
Embodiment 15, embodiment 16, embodiment 17, embodiment 18, the pH value of embodiment 21 are all higher than 6.4, are less than
7.8；Bigger than the compositions of prior art pH value in water, and closer to Human Physiology neutral value, thus more
Good or advantageously, more useful to body.It addition, particularly to acidosic patient, be further added by chlorine in body
The concentration of ion can make the exacerbation of symptoms of metabolic acidosis, for the patient of the renal failure of light moderate.And implement
Example 2, embodiment 19 pH value more than 8, in acidosic situation or to improve acidic physique more meaningful.Relying of alkalescence
Propylhomoserin or 1B or tend to the L-lysine acetate of alkalescence or lysine acetate is more more valuable than lysine hydrochloride or more
Good safety.Thus, the present invention compositions have more reality and Long Significance or clinical value, especially in advance
Anti-potential untoward reaction aspect.
The compositions of the five dimension lysines taking the present invention seals (each embodiment method system in by specific embodiment in plastic bottle
Standby sample), be placed in temperature be 30 DEG C ± 2 DEG C, relative humidity be to test 6 months, respectively at examination under the conditions of 75% ± 5%
Test quality of taking a sample to check 0,6 the end of month.The detection method of content list of references document of 1B: five dimension lysines
Grain, national drug standards WS-10001-(HD-0597)-2002), wherein L-lysine acetate or lysine acetate or bad
The content of propylhomoserin or 1B or LYS respectively with L-lysine acetate or lysine acetate or lysine or
1B or LYS reference substance carry out blank determination, convert according to its stoichiometry, main in capsule
Need during the mensuration of medicine to remove, by the fine powder of its content with reference to tablet or the side of granule national standard capsule shell
Method is measured.Experiment finds, LYS or L-acetic acid by the seal-packed present invention of plastic drug package rely
Propylhomoserin or lysine acetate or lysine or 1B and five kinds of vitamin combination capsules or tablet or granule are (each
Embodiment sample) (in each embodiment, the inventory of each component is labelled amount), measure accelerated test 0 month and 6 months
Sample, finds that its character, content etc. have no significant change, and meets convention or the regulation of standards of pharmacopoeia.The results are shown in Table 1.
The compositions of the five dimension lysines of the present invention, it is adaptable to preparation is for preventing and treating being used for of people and mammal
Promote child, Children Normal growth promoter and the nutritional supplementation of elderly and infirm, or the patient that other 1B lacks
Supplement 1B or metabolic acidosis, hyperchloremia but need to mend lysine and vitamin, inappetence, battalion
Support in bad and cerebral dysgenesis, rickets, craniocerebral trauma, the medicine preventing osteoporosis etc. or health food
Application.
The pharmaceutical composition of five dimension lysines that are that the invention provides improvement or that more have advantage, the present invention the most also embodies
Further advantage is: 1, provide LYS, a vitamin B1, vitamin B2, vitamin B6, nicotiamide,
D-VB5 calcium or the new compositions of D-VB5 calcium 2 hydrate, provide in a unit dose and more effectively can inhale
Receive the 1B utilized, contribute to the growth promoter etc. of people or mammal；2, offer is different from compositions in the past
LYS, vitamin B1, vitamin B2, vitamin B6, nicotiamide, D-VB5 calcium or D-VB5 calcium
The compositions of the new weight ratio of 2 hydrates；3, lysine or 1B or lysine acetate or L-acetic acid is provided to rely ammonia
Acid and, vitamin B1, vitamin B2, vitamin B6, nicotiamide, D-VB5 calcium or D-VB5 calcium 2 hydrate
Compositions, the incidence rate that when reducing clinical administration, the untoward reaction such as hyperchloremia or acidosis is potential；4, rely containing hydrochloric acid
The compositions of propylhomoserin is also unfavorable for the treatment of autism children, to that suffer from infantile autism but require supplementation with five dimension lysines
The patient of pharmaceutical composition, it is provided that one is safer and more effective or more select, this most current pharmacy or clinical institute
Ignore or have no promotion；5, for occurring or easily occur the patient of acidosis or hyperchloremia to provide new selection, or
Reduce potential untoward reaction so that the safety of clinical treatment improves.6, a unit formulation of prior art preparation
Middle drug content is the lowest, only contains lysine hydrochloride and the 0.15mg calcium pantothenate of 50mg, and oral dose is at needs
When exceeding or require more than above dosage or expand the crowd of being suitable for, bring inconvenience, bring pressure to the manufacturing, special
It not in the case of equipment capacity is certain, causes work time cost to be multiplied, give again the packaging having more one or several times,
Bring pressure, the present invention to provide the preparation of compositions of high unit dose to environment, give and manufacture equal daily dose
Drug release one times or the production capacity of several times also make environment become friendly.7, the compositions that the present invention obtains, preparation specification
The lysine hydrochloride of the racemization that the compositions sheet of identical LYS or L-lysine acetate is more identical than preparation specification
Compositions be more easy to rapidly enter blood circulation and reach effectively to treat concentration, there is more significantly clinical advantage.
8, compositions or the preparation of high drug content of the high-load of new unit dose are provided, save at double production, packaging,
The resources such as inspection, transport.
Detailed description of the invention
Except in an embodiment and indicated otherwise time, all of numerical value used in specification and claims should be by
Be interpreted as modifying with term " about " in all of example, therefore, unless the contrary indication, this specification and
The numerical parameter gone out given in appending claims is approximation, and it can be according to by sought by present disclosure
Required character and change, at least, and be not intended to limit the application of doctrine of equivalents right,
Each numerical parameter is considered as the number of significant digits and the routine method of rounding up is explained.
Although the numerical range and the parameter that set the wide scope of disclosure are approximations.But institute in a particular embodiment
The numerical value be given is reported as precisely as possible, and any number substantially comprises some and sent out by the test of each of which
The error that existing standard deviation is necessarily led to.
It is pointed out that unless literary composition the most additionally illustrates, use in this specification and the appended claims
Singulative " ", " a kind of " and " being somebody's turn to do " include the plural form that refers to thing, so, such as.If mentioning and containing
The mixture of two or more compound is included, it is further noted that remove when having the compositions of " a kind of compound "
Non-the most additionally illustrating, term "or" generally includes "and/or".
Drug content in each embodiment all can be according to the 80-120% of the 90-110% of its labelled amount or labelled amount for closing
The specification of lattice.
" pharmaceutical composition " used herein refers to the compositions of medicine, and described pharmaceutical composition can contain at least one
Pharmaceutically acceptable carrier.
It is medicinal that " pharmaceutically acceptable excipient " used herein refers to that the compound being applicable to occasionally provide herein is administered
Carrier or solvent, it includes well known to a person skilled in the art any examples of such carriers being applicable to specific administration mode,
Ethanol water about 95% or the alcohol water blend of 95%, i.e. refer to that both volume ratios are: ethanol: water=95:5,
The ethanol water of 90% or alcohol water, i.e. both volume ratios be: ethanol: water=90:10, below or remaining is similar.
In order to further appreciate that the present invention, below in conjunction with embodiment, the preferred embodiment of the invention is described, but
Should be appreciated that these describe simply for further illustrating the features and advantages of the present invention rather than wanting right of the present invention
The restriction asked.
The preparation of embodiment 1 five dimension 1B capsule, prescription (1000): LYS 50g, dimension
Raw element B11.2g, vitamin B20.15g, vitamin B60.075g, nicotiamide 2.4g, D-VB5 calcium or D-VB5
Calcium 2 hydrate 0.15g；Preparation technology: LYS that take recipe quantity, that cross 100 mesh sieves respectively, dimension are raw
Element B1, vitamin B2, vitamin, nicotiamide, D-VB5 calcium, by equal increments dilution method mix homogeneously, survey granule
The content of middle principal agent LYS, according to dosage fill capsule, pack, check, obtain goods.
The preparation of embodiment 2 five dimension 1B capsule, prescription (1000): 1B 40g, vitamin
B11.2g, vitamin B20.15g, vitamin B60.075g, nicotiamide 2.4g, D-VB5 calcium 2 hydrate 0.15g；
Preparation technology: each component that take recipe quantity, that cross 100 mesh sieves respectively by by equal increments method dilution method mix homogeneously,
Survey the content of principal agent 1B, according to dosage fill capsule in granule, pack, check, obtain goods.
Embodiment 3 L-five ties up the preparation of lysine capsule, prescription (1000): L-lysine acetate 56.458g,
Vitamin B11.2g, vitamin B20.15g, vitamin B60.075g, nicotiamide 2.4g, D-VB5 calcium 0.15g；System
Standby technique: each component that take recipe quantity, that cross 100 mesh sieves respectively is progressively increased dilution method mix homogeneously according to equivalent, surveys
The content of LYS in Li, qualified after according to dosage fill capsule, pack, check, obtain goods.
Embodiment 4L-five ties up preparation (prescription (1000) LYS 45g, the dimension life of lysine capsule
Element B11.44g, vitamin B20.12g, vitamin B60.09g, nicotiamide 2.12g, D-VB5 calcium 0.18g, tristearin
Acid magnesium 1g；Preparation technology: take recipe quantity, respectively cross 100 mesh sieves each component according to equivalent progressively increase dilution method mixing
Uniformly, survey the content of principal agent LYS, according to dosage fill capsule in granule, pack, check, obtain goods.
Embodiment 5 L-five ties up the preparation prescription of lysine capsule, prescription (1000): L-lysine acetate 62.10g,
Vitamin B10.96g, vitamin B20.18g, vitamin B60.06g, nicotiamide 2.88g, D-VB5 calcium 2 is hydrated
Thing 0.12g；Preparation technology: take recipe quantity, respectively cross 100 mesh sieves each component according to equivalent progressively increase dilution method mixing
Uniformly, fill capsule according to quantity, pack, check, obtain goods.
Embodiment 6 L-five ties up the preparation of lysine capsule, prescription (1000): LYS 52g, dimension
Raw element B11.1g, vitamin B20.16g, vitamin B60.070g, nicotiamide 2.6g, D-VB5 calcium 0.14g, crystallite
Cellulose 50g, low-substituted hydroxypropyl cellulose 8g, micropowder silica gel 1g, the polyvinylpyrrolidone of 5% is appropriate；System
Standby technique: take after pulverizing respectively and cross the LYS of recipe quantity of 100 mesh sieves, vitamin B1, vitamin
B2, vitamin B6, nicotiamide, D-VB5 calcium, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose progressively increase according to equivalent
Dilution method mix homogeneously；Polyvinylpyrrolidone (alcohol water of about 90%) solution soft material the most processed with 5%, mistake
40 mesh sieves are pelletized, about 50 DEG C forced air dryings 2 hours, after crossing 40 mesh sieve granulate, with the micropowder silica gel crossing 100 mesh sieves
Mixing；Survey the content of LYS, according to dosage fill capsule in granule, pack, check, obtain goods.
The preparation prescription (1000) of embodiment 7 five dimension lysine capsule: L-lysine acetate 54g, vitamin
B11.3g, vitamin B20.14g, vitamin B60.08g, nicotiamide 2.3g, D-VB5 calcium 0.17g, microcrystalline cellulose
Element 60g, low-substituted hydroxypropyl cellulose 10g, micropowder silica gel 1g, the polyvinylpyrrolidone of 5% is appropriate；Preparation work
Skill: take after pulverizing respectively and cross the L-lysine acetate of recipe quantity of 100 mesh sieves, vitamin B1, vitamin B2, dimension
Raw element B6, nicotiamide, D-VB5 calcium, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose progressively increase dilution method according to equivalent
Mix homogeneously；Polyvinylpyrrolidone (alcohol water of about 90%) solution soft material the most processed with 5%, crosses 40 mesh sieves
Pelletizing, about 50 DEG C forced air dryings 2 hours, after crossing 40 mesh sieve granulate, with the micropowder silica gel mixing crossing 100 mesh sieves；
Survey the content of L-lysine acetate, fill capsule according to quantity in granule, pack, check, obtain goods.
Embodiment 8 L-five ties up the preparation prescription (1000) of lysine capsule: lysine acetate 60g, vitamin
B11.2g, vitamin B20.15g, vitamin B60.08g, nicotiamide 2.4g, D-VB5 calcium 0.15g；Preparation technology:
Each component that take recipe quantity, that cross 100 mesh sieves respectively is progressively increased dilution method mix homogeneously according to equivalent；Fill capsule according to quantity,
Packaging, inspection, obtain goods.
Embodiment 9 L-five ties up the preparation prescription (1000 bags) of lysine particle agent: LYS 150g, dimension
Raw element B13.6g, vitamin B20.45g, vitamin B60.225g, nicotiamide 7.2g, D-VB5 calcium or D-VB5 calcium
2 hydrate 0.45g, sucrose 3000g；Preparation technology: take recipe quantity, respectively cross 100 mesh sieves each component by
Progressively increase dilution method mix homogeneously according to equivalent, progressively increase dilution method mix homogeneously according to equivalent, survey principal agent L-hydrochloric acid in granule and rely
The content of propylhomoserin, is according to dosage sub-packed in double aluminum composite membrane packaging bag, seals, checks, obtain goods.
Embodiment 10 L-five ties up the preparation prescription (1000 bags) of lysine particle agent: LYS 50g, dimension
Raw element B11.2g, vitamin B20.15g, vitamin B60.075g, nicotiamide 2.4g, D-VB5 calcium or D-VB5
Calcium 2 hydrate 0.15g, xylitol 945g；Preparation technology: take recipe quantity, respectively cross 100 mesh sieves each component by
Progressively increase dilution method mix homogeneously according to equivalent；Survey the content of principal agent LYS in granule, be according to dosage sub-packed in double aluminum
In composite film packaging bag, seal, check, obtain finished product.
Embodiment 11 L-five ties up the preparation prescription (1000 bags) of lysine particle agent: LYS 48g, dimension
Raw element B11.44g, vitamin B20.13g, vitamin B60.08g, nicotiamide 2.22g, D-VB5 calcium 2 hydrate
0.17g, sucrose 20g, xylitol 600g, Gardenia Yellow 1g, low-substituted hydroxypropyl cellulose 30g, the poly-second of 5%
Alkene pyrrolidone is appropriate；Preparation technology: take respectively pulverize after and cross 100 mesh sieves recipe quantity LYS,
Vitamin B1, vitamin B2, vitamin B6, nicotiamide, D-VB5 calcium 2 hydrate, sucrose, xylitol, Fructus Gardeniae
Flavochrome, low-substituted hydroxypropyl cellulose progressively increase dilution method mix homogeneously according to equivalent；With the polyvinylpyrrolidone of 5%
(alcohol water of about 90%) solution soft material the most processed, crosses 60 mesh sieves and pelletizes, about 50 DEG C forced air dryings 2 hours, mistake
After 40 mesh sieve granulate, survey the content of principal agent LYS in granule, be according to dosage sub-packed in double aluminum composite membrane packaging bag
In, seal, check, obtain finished product.
Embodiment 12 L-five ties up the preparation prescription (1000 bags) of lysine particle agent: LYS 100g, dimension
Raw element B12.4g, vitamin B20.30g, vitamin B60.15g, nicotiamide 4.8g, D-VB5 calcium 2 hydrate 0.3g,
Xylitol 200g；Preparation technology: take recipe quantity, cross each component after 60 mesh sieves respectively and progressively increase dilution method according to equivalent
Mix homogeneously, surveys the content of principal agent LYS in granule, is according to dosage sub-packed in double aluminum composite membrane packaging bag,
Sealing, inspection, obtain finished product.
Embodiment 13 L-five ties up the preparation prescription (1000 bags) of lysine particle agent: L-lysine acetate 56.458g,
Vitamin B11.2g, vitamin B20.15g, vitamin B60.075g, nicotiamide 2.4g, D-VB5 calcium 0.15g,
Saccharin sodium 2g, xylitol 940g；Preparation technology: take recipe quantity, respectively cross 40～60 mesh sieves, take after sieving
Each component is progressively increased dilution method mix homogeneously according to equivalent；Survey the content of principal agent L-lysine acetate in granule, according to dosage divide
It is loaded in double aluminum composite membrane packaging bag, seals, check, obtain finished product.
Embodiment 14 L-five ties up the preparation prescription (1000 bags) of lysine particle agent: L-lysine acetate 56.458g,
Vitamin B11.2g, vitamin B20.15g, vitamin B60.075g, nicotiamide 2.4g, D-VB5 calcium 0.15g,
Sorbitol 500g, low-substituted hydroxypropyl cellulose 30g, the polyvinylpyrrolidone of 5% is appropriate；Preparation technology: take
With the LYS of recipe quantity of 100 mesh sieves, vitamin B excessively after pulverizing respectively1, vitamin B2, vitamin
B6, nicotiamide, D-VB5 calcium 2 hydrate, sorbitol, low-substituted hydroxypropyl cellulose progressively increase dilution method according to equivalent
Mix homogeneously；Polyvinylpyrrolidone (alcohol water of about 90%) solution soft material the most processed with 5%, crosses 60 mesh sieves
Pelletize, about 50 DEG C forced air dryings 2 hours, cross 40 mesh sieve granulate, survey the content of L-lysine acetate in granule, point
It is not sub-packed in double aluminum composite membrane packaging bag according to different dosage strengths, seals, check, to obtain final product.
Embodiment 15 L-five ties up the preparation prescription (1000 bags) of lysine particle agent: L-lysine acetate 112.92g,
Vitamin B12.4g, vitamin B20.30g, vitamin B60.15g, nicotiamide 4.8g, D-VB5 calcium 2 hydrate
0.3g, xylitol 300g；Preparation technology: take recipe quantity, cross each component after 80 mesh sieves respectively and progressively increase according to equivalent
Dilution method mix homogeneously；Survey the content of principal agent L-lysine acetate in granule, be according to dosage sub-packed in double aluminum composite membrane packaging
In Dai, seal, check, obtain corresponding preparation.
Embodiment 16 L-five ties up the preparation prescription (1000 bags) of lysine particle agent: L-lysine acetate 169.37g,
Vitamin B13.6g, vitamin B20.45g, vitamin B60.225g, nicotiamide 7.2g, D-VB5 calcium or D-VB5
Calcium 2 hydrate 0.45g, xylitol 300g；Preparation technology: take recipe quantity, cross each component after 60 mesh sieves respectively
Progressively increase dilution method mix homogeneously according to equivalent；Survey the content of L-lysine acetate in granule, be according to dosage sub-packed in double aluminum multiple
Close in film package bag, seal, check, obtain finished product.
Embodiment 17 L-five ties up the preparation prescription (1000 bags) of lysine particle agent: L-lysine acetate 248.41g,
Vitamin B15.28, vitamin B20.66g, vitamin B60.33g, nicotiamide 10.56g, D-VB5 calcium or D-are general
Acid calcium 2 hydrate 0.66g, sucralose 1g, xylitol 360g；Preparation technology: take recipe quantity, respectively cross 60
Each component after mesh sieve is progressively increased dilution method mix homogeneously according to equivalent；Survey the content of L-lysine acetate in granule, by agent
Amount is sub-packed in double aluminum composite membrane packaging bag, seals, checks, obtains finished product.
The preparation prescription (1000 bags) of embodiment 18 5 dimension lysine particle agent: lysine acetate 112.92g, dimension
Raw element B12.4g, vitamin B20.30g, vitamin B60.15g, nicotiamide 4.8g, D-VB5 calcium 2 hydrate 0.3g,
Xylitol 200g；Preparation technology: take recipe quantity, cross each component after 60 mesh sieves respectively and progressively increase dilution method according to equivalent
Mix homogeneously；Survey the content of lysine acetate in granule, be sub-packed in double aluminum composite membrane packaging bag according to dosage strengths,
Sealing, inspection, obtain corresponding preparation.
The preparation prescription (1000 bags) of embodiment 19 5 dimension lysine particle agent: lysine 42g, vitamin B11.2
G, vitamin B20.15g, vitamin B60.075g, nicotiamide 2.4g, D-VB5 calcium 0.15g, saccharin sodium 2g, wood
Sugar alcohol 956g, Gardenia Yellow 1g；Preparation technology: take recipe quantity, respectively cross each component after 60 mesh sieves according to
Equivalent is progressively increased dilution method mix homogeneously, surveys the content of L-lysine acetate in granule, is according to dosage sub-packed in double aluminum composite membrane
In packaging bag, seal, check, obtain finished product.
Embodiment 20 L-five ties up the preparation prescription (1000 bags) of lysine suspensoid: LYS 50g, dimension
Raw element B11.2g, vitamin B20.15g, vitamin B60.075g, nicotiamide 2.4g, D-VB5 calcium or D-VB5
Calcium 2 hydrate 0.15g, xylitol 300g, xanthan gum 1g；Preparation technology: take recipe quantity, respectively cross 80 mesh sieves
After each component progressively increase dilution method mix homogeneously according to equivalent, survey the content of LYS in granule, according to dosage divide
It is loaded in double aluminum composite membrane packaging bag, seals, check, obtain finished product.
Embodiment 21 L-five ties up the preparation of lysine suspensoid, prescription (1000 bags): L-lysine acetate 62.458g,
Vitamin B11.2g, vitamin B20.17g, vitamin B60.075g, nicotiamide 2.6g, D-VB5 calcium 2 hydrate
0.18g, xylitol 940g, xanthan gum 1g；Preparation technology: take recipe quantity, cross each component after 80 mesh sieves respectively
Progressively increase dilution method mix homogeneously according to equivalent, survey the content of L-lysine acetate in granule, be according to dosage sub-packed in double aluminum multiple
Close in film package bag, seal, check, obtain finished product.
Embodiment 22 L-five ties up lysine tablet formulation (1000): LYS 50g, vitamin B11.2
G, vitamin B20.15g, vitamin B60.075g, nicotiamide 2.4g, D-VB5 calcium or D-VB5 calcium 2 hydrate
0.15g, lactose 20g, microcrystalline Cellulose 30g, low-substituted hydroxypropyl cellulose 10g, aspartame 1g, micropowder silica gel
2g, the polyvinylpyrrolidone of 5% is appropriate；
Preparation technology: take after pulverizing respectively and cross the LYS of recipe quantity of 100 mesh sieves, vitamin B1, dimension
Raw element B2, vitamin B6, nicotiamide, D-VB5 calcium or D-VB5 calcium 2 hydrate, lactose, microcrystalline Cellulose,
Low-substituted hydroxypropyl cellulose, aspartame progressively increase dilution method mixing according to equivalent, then the polyvinylpyrrolidone with 5%
(alcohol water of about 85%) solution soft material the most processed, crosses 40 mesh sieves and pelletizes, about 50 DEG C forced air dryings 2 hours, mistake
After 40 mesh sieve granulate, with the micropowder silica gel mixing crossing 100 mesh sieves；Being crossed 40 mesh sieves, granulate, in detection intermediate
LYS content, tabletting, pack and get final product.
Embodiment 23 L-five ties up lysine tablet formulation (1000): L-lysine acetate 56.458g, vitamin
B11.2g, vitamin B20.15g, vitamin B60.075g, nicotiamide 2.4g, D-VB5 calcium 0.15g, microcrystalline cellulose
Element 100g, low-substituted hydroxypropyl cellulose 10g, micropowder silica gel 1.2g, the polyvinylpyrrolidone of 5% is appropriate；
Preparation technology: take after pulverizing respectively and cross the L-lysine acetate of recipe quantity of 100 mesh sieves, vitamin B1, dimension
Raw element B2, vitamin B6, nicotiamide, D-VB5 calcium or D-VB5 calcium 2 hydrate, microcrystalline Cellulose, low replacement
Hydroxypropyl cellulose mix homogeneously；Polyvinylpyrrolidone (alcohol water of about 90%) solution with 5% is made soft in right amount
Material, crosses 40 mesh sieves and pelletizes, about 50 DEG C forced air dryings 2 hours, after crossing 40 mesh sieve granulate, and crosses 100 mesh sieves
Micropowder silica gel mixes；Detection intermediate L-lysine acetate content, tabletting, pack and get final product.
Embodiment 24 L-five ties up the preparation prescription (1000) of lysine tablet: L-lysine acetate 112.92g,
Vitamin B12.4g, vitamin B20.30g, vitamin B60.15g, nicotiamide 4.8g, D-VB5 calcium 2 hydrate
0.3g, starch 50g, microcrystalline Cellulose 120, carboxymethyl starch sodium 20g, micropowder silica gel 8g, about 3% hydroxypropyl first
Base cellulose is appropriate；
Preparation technology: take after pulverizing respectively and cross the LYS of recipe quantity of 100 mesh sieves, vitamin B1, dimension
Raw element B2, vitamin B6, nicotiamide, D-VB5 calcium or D-VB5 calcium 2 hydrate, starch, microcrystalline Cellulose,
Carboxymethyl starch sodium mix homogeneously；Make soft in right amount with 3% hydroxypropyl methyl cellulose (alcohol water of about 80%) solution
Material, crosses 40 mesh sieves and pelletizes, about 50 DEG C forced air dryings 2 hours, after crossing 40 mesh sieve granulate, and crosses 100 mesh sieves
Micropowder silica gel mixes, the L-lysine acetate content in detection intermediate, and tabletting is packed and be get final product.
The pharmaceutical composition of the five dimension lysines that embodiment 25 takes the present invention seals lucifuge in suitable plastic drug package and (presses
In specific embodiment, each embodiment method prepares each sample respectively, with sheet or capsule or bag for minimum dose unit), it is placed in
Temperature is 30 DEG C ± 2 DEG C, relative humidity is to carry out 6 months Acceleration study under the conditions of 75% ± 2% to investigate its stability, point
Not in 0,6 sampling detections at the end of month of test, find that its character is without substantially changing；List of references " the national drug standards five
Dimension lysine particle, national drug standards WS-10001-(HD-0597)-2002 " in lysine assay method and in
State's pharmacopeia, about the assay method etc. in capsule, granule, finds after measured, the principal agent component equal nothing of 1B content
Significant change, changes of contents, all in the range of the 90-110% of labelled amount, the results are shown in Table 1.
Table 1 stability test result
The rat of embodiment 26 compositions is administered experiments experiment animal: be born about about surrounding, body weight is about 74～91
Gram, the Wistar male white rat 80 that is in a good state of health, ablactation；It is divided into four according to rat body weight uniform distribution rat
Group, often group rat n=20 is only so that the average weight between each group rat before experiment there was no significant difference, and A group is empty
White matched group, gives normal feedstuff and raises；B, C, D are administration group, give the principal agent group that normal feedstuff adds the present invention
The mixed fodder of compound is raised, and contains the Different Weight of this most tested principal agent compositions 1.5 grams respectively with every 100g normal feedstuff
Each correspondent composition powder of ratio or the mixed fodder of granule are fed rat；Wherein, B group is the combination of lysine hydrochloride
(principal agent composition weight proportioning is thing group: 50:1.2:0.15:0.075:2.4:0.15, relies with DL-hydrochloric acid respectively
Propylhomoserin, vitamin B1, vitamin B2, vitamin B6, nicotiamide, each composition weight of calcium pantothenate meter)；C group is containing L-
The compositions group (principal agent compositions proportioning: such as embodiment 21) of lysine acetate；D group is containing LYS
Compositions group (principal agent compositions proportioning: such as the principal agent ratio of embodiment 1)；B, C, D respectively organize respectively with normal feedstuff with
The compositions of each group is fed after carrying out preparing mixing, and the normal feedstuff amount of each group input every day keeps equalization, freely drinks water
And ingest；Often group rat is fed five weeks, claims every rat body weight, experiment to claim its body weight to the 5th weekend before experiment,
Net gain after five weeks, the average that calculating is often organized, Analysis of variance, found that each experimental group of C, D and A group and B
The difference of group all has significance, its p value 0.05；Experimental result is shown in Table 2.
The rat of table 2 five dimension lysine medicament compound is administered experimental result
Industrial applicibility etc. and explanation etc. thereof:
Above by detailed description of the invention and embodiment, the present invention is described in detail, it will nevertheless be understood that these are said
Bright not to the scope of the present invention any restriction of composition, person skilled substantially can be in the spirit without departing from the present invention
In the case of protection domain, technical solutions and their implementation methods of the present invention can be carried out multiple modification, improvement and
Replacing and combination, realize the technology of the present invention, these are all because falling within the scope of protection of the present invention.Of particular note
Be, it will be understood that the change of a lot of details is possible, all similar replacements and changing art technology
Being apparent from for personnel, they are considered as being included in the spirit of the present invention, scope and content, the present invention
It is not limited to above-described embodiment.
Claims (9)
1. the compositions of five dimension lysines, it is characterised in that: principal agent in the said composition of a unit dose or unit formulation
The weight of component or weight ratio be: LYS or its solvated compounds 45.0～220mg or L-acetic acid
Lysine or lysine acetate or its solvated compounds 50.81～248.41mg or lysine or 1B or
Its solvated compounds 36.02～176.08mg, vitamin B1Or its solvated compounds 0.96～5.28mg, dimension is raw
Element B2Or its solvated compounds 0.12～0.66mg, vitamin B6Or its solvated compounds 0.06～0.33mg,
Nicotiamide or its solvated compounds 2.12～10.56mg, D-VB5 calcium or D-VB5 calcium 2 hydrate 0.12～
0.66mg；Wherein, the solvated compounds of each principal agent component calculates when being all converted into solvent free compound according to it
Weight.
The compositions of five dimension lysines the most according to claim 1, it is characterised in that: a unit dose or unit
In the said composition of preparation, weight or the weight ratio of principal agent component are: LYS or its solvated compounds
45.0～220mg or L-lysine acetate or lysine acetate or its solvated compounds 50.81～248.41mg or
Lysine or 1B or its solvated compounds 36.02～176.08mg, vitamin B1Or its solvent chemical combination
Thing 0.96～5.28mg, vitamin B2Or its solvated compounds 0.12～0.66mg, vitamin B6Or its solvent
Compound 0.06～0.33mg, nicotiamide or its solvated compounds 2.12～10.56mg, D-VB5 calcium or D-
Calcium pantothenate 2 hydrate 0.12～0.66mg；And pharmaceutically acceptable one or more adjuvants or carrier；
Wherein, the calculated weight when solvated compounds of each principal agent component is all converted into solvent free compound according to it.
The compositions of the five dimension lysines the most according to claims 1 to 2, it is characterised in that: a unit dose or
In the said composition of unit formulation, the weight ratio of principal agent component is: LYS or its solvated compounds
45.0～55mg or L-lysine acetate or lysine acetate or its solvated compounds 50.81～62.10mg or rely
Propylhomoserin or 1B or its solvated compounds 36.02～44.02mg, vitamin B1Or its solvated compounds
0.96～1.44mg, vitamin B2Or its solvated compounds 0.12～0.18mg, vitamin B6Or its solvation
Compound 0.06～0.09mg, nicotiamide or its solvated compounds 2.12～2.88mg, D-VB5 calcium or D-VB5
Calcium 2 hydrate 0.12～0.18mg；And pharmaceutically acceptable one or more adjuvants or carrier；Wherein,
The calculated weight when solvated compounds of each principal agent component is all converted into solvent free compound according to it.
The compositions of the five dimension lysines the most according to claims 1 to 2, it is characterised in that: a unit dose or
In the said composition of unit formulation, weight or the weight ratio of principal agent component are: LYS or its solvent chemical combination
Thing 90.0～220mg or L-lysine acetate or lysine acetate or its solvated compounds 100～248.41mg
Or lysine or 1B or its solvated compounds 72～176.08mg, vitamin B1Or its solvated compounds
2.0～5.28mg, vitamin B2Or its solvated compounds 0.24～0.66mg, vitamin B6Or its solvation
Compound 0.12～0.33mg, nicotiamide or its solvated compounds 4.24～10.56mg, D-VB5 calcium or D-VB5
Calcium 2 hydrate 0.24～0.66mg；And pharmaceutically acceptable one or more adjuvants or carrier；Wherein,
The calculated weight when solvated compounds of each principal agent component is all converted into solvent free compound according to it.
The compositions of the five dimension lysines the most according to claims 1 to 3, it is characterised in that: a unit dose or
Compositions in unit formulation contains: LYS or its solvated compounds 50mg or L-acetic acid rely ammonia
Acid or its solvated compounds 56.458mg or 56.46mg56.5mgL-lysine or its solvated compounds 40.019
Mg or 40.02mg or 40mg, vitamin B1Or its solvated compounds 1.2mg, vitamin B2Or it is molten
Immunomodulator compounds 0.15mg, vitamin B6Or its solvated compounds 0.075mg, nicotiamide 2.4mg, D-are general
Acid calcium or D-VB5 calcium 2 hydrate 0.15mg；And pharmaceutically acceptable one or more adjuvants or carrier；
Wherein, the calculated weight when solvated compounds of each principal agent component is all converted into solvent free compound according to it.
The compositions of the five dimension lysines the most according to claims 1 to 2, it is characterised in that: a unit dose or
Compositions in unit formulation contains LYS or its solvated compounds 100mg or L-acetic acid relies ammonia
Acid or lysine acetate or its solvated compounds 112.915mg or 112.92mg or 112.9mg or 113mg or
Lysine or 1B or its solvated compounds 80.0384mg or 80.038mg or 80.04mg or 80mg,
Vitamin B1Or its solvated compounds 2.4mg, vitamin B2Or its solvated compounds 0.30mg, vitamin
B6Or its solvated compounds 0.15mg, nicotiamide 4.8mg, D-VB5 calcium or D-VB5 calcium 2 hydrate
0.30mg；And pharmaceutically acceptable one or more adjuvants or carrier；Wherein, each principal agent component is molten
Calculated weight when immunomodulator compounds is all converted into solvent free compound according to it.
The compositions of the five dimension lysines the most according to claims 1 to 2, it is characterised in that: a unit dose or
Compositions in unit formulation contains LYS or its solvated compounds 150mg or L-acetic acid relies ammonia
Acid or lysine acetate or its solvated compounds 169.3731mg or 169.373mg or 169.37mg or
169.4mg or 170mg or 169mg or lysine or 1B or its solvated compounds 120.058mg or
120.06mg or 120mg or 120.1mg, vitamin B1Or its solvated compounds 3.6mg, vitamin B2
Or its solvated compounds 0.45mg, vitamin B6Or its solvated compounds 0.225mg, nicotiamide 7.2mg,
D-VB5 calcium or D-VB5 calcium 2 hydrate 0.45mg；And pharmaceutically acceptable one or more adjuvants or
Carrier；Wherein, the calculated weight when solvated compounds of each principal agent component is all converted into solvent free compound according to it.
The compositions of five dimension lysines the most according to claims 1 to 7, it is characterised in that: its purposes is: should
Compositions individually or with pharmaceutically acceptable adjuvant in preparing tablet, granule, capsule, suspensoid should
With.
The compositions of five dimension lysines the most according to claims 1 to 7, it is characterised in that: its purposes is: system
For preventing or treating people and mammal lysine shortage, calcium deficiency, retarded growth, inappetence, battalion
Support the application in bad, the health food of rickets, osteoporosis, craniocerebral trauma or medicine.
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Cited By (1)
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| CN110227079A (en) * | 2019-06-04 | 2019-09-13 | 延边大学草仙药业有限公司 | One kind five ties up lysine particle and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110227079A (en) * | 2019-06-04 | 2019-09-13 | 延边大学草仙药业有限公司 | One kind five ties up lysine particle and preparation method thereof |
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Application publication date: 20161207 |