CN104688774A

CN104688774A - Lysine and calcium hydrophosphate pharmaceutical composition comprising chiral isomeric compound and application of pharmaceutical composition

Info

Publication number: CN104688774A
Application number: CN201510086109.6A
Authority: CN
Inventors: 刘力
Original assignee: Individual
Current assignee: Individual
Priority date: 2015-02-17
Filing date: 2015-02-17
Publication date: 2015-06-10

Abstract

The invention provides a pharmaceutical composition of lysine and calcium hydrophosphate or dihydrate of the calcium hydrophosphate, which comprises a chiral isomeric compound, and is used for preventing or treating L-lysine and calcium deficiency, retarded growth of children and teenagers, osteoporosis, metabolic acidosis and brain trauma, and regulating blood pressure and the like, a preparation method of the pharmaceutical composition, and an application of the pharmaceutical composition as health foods or medicines. The obtained product has new intended population, or relatively good pertinence and clinical safety in clinical application.

Description

Comprise the lysine calcium mono hydrogen phosphate medical composition and its use of chiral photo-isomerisation compound

Technical field

The present invention relates to medical art, be specifically to provide the lysine comprising chiral photo-isomerisation compound of prevention or treatment calcium deficiency etc. and the pharmaceutical composition of calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate and preparation thereof and purposes.

Background technology

Calcium ion is the indispensable ion of the every physiological activity of body.It is for the bioelectric potential maintaining cell membrane both sides, and maintain normal Nerve conduction etc., some functions of hormones mechanism are all showed by calcium ion.Main Function or mechanism are:

1, calcium ion is thrombin, participates in coagulation process;

2, participate in muscle (comprising skeletal muscle, smooth muscle) contraction process, impel heartbeat.

3, neurotransmitter synthesis and release, hormone sensitive lipase gene and secretion is participated in, and afferent nerve signal.When body calcium deficiency, the release of neurotransmitter is intercepted, and excitatory mechanism and the suppression mechanism of human body are destroyed.If child's calcium deficiency, can night cry, fright at night, irritated insomnia, serious causes brain development obstacle, occurs the disease such as bradykinesia, many dynamic, learning difficulty, affect brain maturation and intelligence.

4, be the important substance that skeleton is formed.

5, signal of resisting the enemy is transmitted.Its mechanism is: when exotic antigen activated T cell receptor, start the signal path of calcium-mediated, impel immune cell differentiation and growth.When the foreign invaders such as pathogenic bacteria, antibacterial, poisonous substance invade human body, first calcium ion sends early warning signal; Calcium ion sends again the signal what characteristic invader has subsequently, and immune system organizes corresponding immunocyte thereupon, catches and engulfs enemy.Once calcium deficiency, function of immune system decline, disorder will be there is, diseases induced.As: autoimmune disease lupus erythematosus, rheumatism; Dermatosis: dermatitis, acne etc.Replenish the calcium, these diseases for the treatment of are played an important role, the function of calcium of having given counterevidence.

But usual Oral Calcium Preparations is only 1/5 ~ 1/3 by intestinal absorption, and the plasma protein binding rate about 45% of calcium, Oral Calcium Preparations about 80% is from defecate.

Lysine belongs to basic amino acid, has DL lysine, D-Lys, 1B three kinds of primitive forms, and 1B is that human body must one of 8 seed amino acids, and 1B provides structural constituent for synthetic carnitine, and carnitine can impel the synthesis of fatty acid in cell.Particularly in childhood development phase, after being ill convalescent period, pregnant lactication phase, higher to the requirement of 1B.Because content is lower in the food such as rice, Semen Maydis, easily cause human body to lack, be called as " the first lack amino acid ".

1B shortage can cause dysplasia, inappetence, loses weight, negative nitrogen balance, hypoproteinemia, hypoplasia of tooth, anemia, enzymatic activity decline and other physiological function obstacle.1B is improved intelligence, growth promoting effects, health invigorating; Appetite stimulator, improve malnutrition situation; Improve insomnia, improve memory; Help to produce antibody, hormone and enzyme, improve immunity, increase hematochrome; Help the absorption of calcium, treatment prevents osteoporosis; Help nervous tissue to repair, promote nervous cell regenerating, improve the effect of central nervous tissue function.Lysine can improve blood-brain barrier permeability; contributing to medicine enters in brain cell; the clinical cerebral protective agent being used as treatment craniocerebral trauma, chronic cerebral tissue ischemia, ischemic disease; or the auxiliary treatment to other encephalopathys; also can be used for 1B lack cause children's's inappetence, (Liu Xiaolan, etc., the medical applications new development of 1B for malnutrition and cerebral dysgenesis; the modern internal medicine magazine of China, 2006 (3) 8:923-924).

At present, the disclosed bibliographical information composite preparation of lysine hydrochloride calcium hydrogen phosphate (document: Chinese patent CN1943594; Lysine calcium mono hydrogen phosphate sheet, national standard WS-10001-(HD-0388)-2002; The national standard of lysine calcium mono hydrogen phosphate granule, WS-10001-(HD-0389)-2002).But not yet there is open source literature to report the compositions of LYS L-lysine acetate or lysine acetate or lysine or 1B and calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate.The more important thing is that the preparation of prior art exists shortcomings or deficiency! Containing the D-Lys of half and 1B in lysine, only 1B is just easily absorbed by body, has larger value to human body, and D-Lys is not easily absorbed by the body utilization; Although also openly report the L-lysine hydrochloride granule of single optical isomer at present, be only limitted to one-component administration.In addition, also there is the patient being not suitable for hyperchloremia, acidosis and renal insufficiency etc. in some cases in compound recipe lysine calcium mono hydrogen phosphate of the prior art or sheet or granule, especially when unknown or take when being difficult to know and may bring adverse consequences in advance; And do not limit in current preparation and use 1B, this makes the quality of preparation or nutrition or therapeutic value or is restricted maybe can not be in Optimal State; Moreover, a current unit dosage strengths only has the lysine hydrochloride of 100mg and the calcium hydrogen phosphate of 100mg or sheet or granule, and when or in fact lysine hydrochloride and calcium hydrogen phosphate single taking dose meet or exceed 200mg, 300mg, 400mg, 500mg, 600mg respectively, be unfavorable for the daily convenience taken; In preparation when increase one multiple dose unit, increase the D-Lys that half is not easily absorbed and used, a unit dose is larger, and Time of Administration is longer, wastes larger.This makes in manufacture, on taking convenience, transport and packaging also have problems maybe can not be suitable for clinical practice to the greatest extent; more be unfavorable for saving human resources and building a resource-conserving society; this rough sledding is ignored for many years always and is improved; the actual social resources that cause are wasted; and increase pressure to environmental conservation, but there is not yet and break through old framework.

Summary of the invention

The compositions of involved in the present invention the is lysine calcium mono hydrogen phosphate comprising chiral photo-isomerisation compound and preparation thereof and purposes, what be specifically related to is prevention or the treatment LYS of calcium deficiency or the compositions of L-lysine acetate or lysine acetate or lysine or 1B and calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate and preparation thereof and purposes.

Principal agent component in compositions of the present invention and weight ratio thereof are: LYS or its hydrate 85-115 part or L-lysine acetate or lysine acetate or its hydrate 95.98-130 part or 1B or its hydrate 68.0-92.04 part, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 85-115 part.One independently medicine or health food packaging unit or independently pack in individuality the total amount that the compositions of this weight ratio of the present invention is housed and can change arbitrarily, can change or adjustment with dosage such as 3 daily doses or 5 daily doses or 6 daily doses or 10 daily doses or 12,20,28,30,60,100 etc., this and without prejudice to spirit of the present invention.

The principal agent component of compositions of the present invention and weight ratio thereof can be: LYS or its hydrate 85-115 part or L-lysine acetate or lysine acetate or its hydrate 95.98-130 part or 1B or its hydrate 68.0-92.04 part, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 85-115 part; Or the 0.5-50 of the above-mentioned each principal agent component in above-mentioned said composition doubly; Wherein the hydrate of LYS or L-lysine acetate or lysine acetate or 1B is according to its anhydride calculated weight.Calcium hydrogen phosphate in the present invention or calcium hydrogen phosphate hydrate, also comprise Portugal's calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate; LYS or L-lysine acetate or lysine acetate or lysine or 1B are all containing its hydrate, comprise its 1 hydrate, 2 hydrates or 3 hydrates etc., the weight of the component calcium hydrogen phosphate in compositions of the present invention calculates its inventory with the weight of calcium hydrogen phosphate 2 hydrate for benchmark carries out equivalent.

The principal agent component of the said composition of a unit dose of the present invention or a unit formulation and weight ratio thereof can be: LYS or its hydrate 85-115 part or L-lysine acetate or lysine acetate or its hydrate 95.98-130 part or 1B or its hydrate 68.0-92.04 part, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 85-115 part; Or the 0.5-50 of the above-mentioned each principal agent component in the said composition of an above-mentioned unit dose or a unit formulation doubly, and can 0.5 be minimum multiple unit, calculate the number (0.5 times, 1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 5.5 times, 6 times, 7 times of (or increase or reduce) each component in proportion ... 12 times, 20,24,25 times etc.); Wherein the hydrate of LYS or L-lysine acetate or lysine acetate or 1B is according to its anhydride calculated weight.Calcium hydrogen phosphate in the present invention or calcium hydrogen phosphate hydrate, also comprise Portugal's calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate; LYS or L-lysine acetate or lysine acetate or lysine or 1B are all containing its hydrate, comprise its 1 hydrate, 2 hydrates or 3 hydrates etc., the weight of the component calcium hydrogen phosphate in compositions of the present invention calculates its inventory with the weight of calcium hydrogen phosphate 2 hydrate for benchmark carries out equivalent.

The pharmaceutical composition of lysine of the present invention and calcium hydrogen phosphate, the said composition of a unit dose or a unit formulation can contain the principal agent component of following weight ratio: LYS 100 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100 parts; The said composition of a unit dose or a unit formulation also can principal agent component containing following weight ratio: L-lysine acetate or lysine acetate 112.92 parts or 112.9 parts or 113 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100 parts, the said composition of a unit dose or a unit formulation also can principal agent component containing following weight ratio: lysine or 1B 80.04 parts or 80.1 parts or 80 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100 parts; Or the 0.5-50 of the above-mentioned each principal agent component in the different compositions of an above-mentioned unit dose or a unit formulation doubly, and can 0.5 be minimum multiple unit, the number (0.5 times, 1 times, 1.5 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times, 5 times, 6 times, 7,8,9,10,11,12,25 times etc.) of (or increase or reduce) each component is calculated according to same ratio.

Pharmaceutical composition of the present invention also comprises as follows: a unit dose or a unit formulation said composition can principal agent component containing following weight ratio:

LYS 100 parts or L-lysine acetate or lysine acetate 113 parts or 1B or its hydrate 80 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100 parts, or the 0.5-50 of above-mentioned each principal agent component is doubly; Or, the said composition of a unit dose or a unit formulation contains the principal agent component of following weight ratio: LYS 110 parts or L-lysine acetate or lysine acetate 130 parts or 1B or its hydrate 92 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 90 parts, or the 0.5-50 of above-mentioned each principal agent component is doubly; Or, the said composition of a unit dose or a unit formulation contains the principal agent component of following weight ratio: LYS 90 parts or L-lysine acetate or lysine acetate 96 parts or 1B or its hydrate 80 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 110 parts, or the 0.5-50 of above-mentioned each principal agent component is doubly; Or, the said composition of a unit dose or a unit formulation contains the component of following weight ratio: LYS or L-lysine acetate or lysine acetate or 1B or its hydrate 90 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100 parts, or the 0.5-12 of above-mentioned each principal agent component is doubly; Or the said composition of a unit dose or a unit formulation contains the component of following weight ratio: LYS or L-lysine acetate 95 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100 parts, or the 0.5-50 of above-mentioned each principal agent component is doubly.The 0.5-50 of the above-mentioned each principal agent component in the different compositions of an above-mentioned unit dose or a unit formulation doubly, 0.5 for minimum multiple unit, the number (0.5 times, 1 times, 1.5 times, 2 times, 2.5 times, 3 times, 4 times, 5 times, 6 times of (or increase or reduce) each component can be calculated in proportion ... 12,24,25,360,40,50 times etc.).

The compositions of lysine calcium mono hydrogen phosphate of the present invention, the principal agent component contained in compositions in a unit dose or a unit formulation is: LYS 1200mg or L-lysine acetate or lysine acetate 1355.04mg or 1355.1mg or 1355mg or lysine or 1B 960.48mg or 960.5mg or 961mg or 960mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 1200mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight, wherein, also other pharmaceutically acceptable adjuvant can be contained.

Or, the principal agent component that can contain in the lysine in a unit dose or a unit formulation and calcium hydrogen phosphate compositions: LYS 1000mg or L-lysine acetate or lysine acetate 1129.2mg or 1129mg or 1130mg or lysine or 1B 800.4mg or 800mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 1000mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B or hydrate are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight, wherein, also other pharmaceutically acceptable adjuvant can be contained.

Or, the principal agent component contained in compositions in a unit dose or a unit formulation is: LYS 600mg or L-lysine acetate or lysine acetate 677.52mg or 677.5mg or 678mg or lysine or 1B 480.24mg or 480.2mg or 480.3 or 481mg or 480mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 600mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight, wherein, also other pharmaceutically acceptable adjuvant can be contained.

Or, the principal agent component contained in compositions in a unit dose or a unit formulation is: LYS 500mg or L-lysine acetate or lysine acetate 564.6mg or 565mg or lysine or 1B 400.2mg or 401mg or 400mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 500mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight, wherein, also other pharmaceutically acceptable adjuvant can be contained.

Or, the principal agent component contained in compositions in a unit dose or a unit formulation is: LYS 400mg or L-lysine acetate or lysine acetate 451.68mg or 451.7mg or 452mg or lysine or 1B 320.16mg or 320.2mg or 320mg or 321mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 400mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight, wherein, also other pharmaceutically acceptable adjuvant can be contained.

Or, the principal agent component contained in compositions in a unit dose or a unit formulation is: LYS 300mg or L-lysine acetate or lysine acetate 338.76mg or 338.8mg or 339mg or lysine or 1B 240.12mg or 240.1mg or 240mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 300mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight, wherein, also other pharmaceutically acceptable adjuvant can be contained.

Or, the principal agent component contained in compositions in a unit dose or a unit formulation: LYS 200mg or L-lysine acetate or lysine acetate 225.84mg or 225.8mg or 226mg or lysine or 1B 160.08mg or 160.1mg or 160mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 200mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight, wherein, also other pharmaceutically acceptable adjuvant can be contained.

Or, the principal agent component contained in lysine in a unit dose or a unit formulation and calcium hydrogen phosphate compositions: LYS 100mg or L-lysine acetate or lysine acetate 112.92mg or 112.9mg or 113mg or lysine or 1B 80.04mg or 80mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B or hydrate are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight, wherein, also other pharmaceutically acceptable adjuvant can be contained.

Or, the principal agent component contained in lysine in a unit dose or a unit formulation and calcium hydrogen phosphate compositions: LYS 50mg or L-lysine acetate or lysine acetate 56.46mg or 56.5mg or 57mg or 56mg or lysine or 1B 40.02mg or 40mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 50mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B or hydrate are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight, wherein, also other pharmaceutically acceptable adjuvant can be contained.

Or, principal agent component containing following weight ratio in the lysine and calcium hydrogen phosphate compositions of a unit dose or a unit formulation: LYS or its hydrate 85-115 part or L-lysine acetate or lysine acetate or its hydrate 95.98-130 part or 1B or its hydrate 68.03-92.04 part, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 85-115 part, or the 0.5-50 containing above-mentioned each principal agent component in the compositions of an above-mentioned unit dose or a unit formulation doubly, and be minimum multiple unit with 0.5, calculate the number (0.5 times of (or increase or reduce) each component in proportion, 1 times, 1.5 doubly, 2 times, 2.5 doubly, 3 times, 4 times, 5 times, 6 times ... 12, 25, 40 times etc.), in addition, one or more pharmaceutically acceptable adjuvant or excipient wherein also containing 0.0001-5000 part, wherein, the calculated weight when hydrate of LYS or L-lysine acetate or 1B is converted into anhydride according to it.

It is to be noted, the principal agent component contained in compositions in a unit dose or a unit formulation: L-lysine acetate or between lysine acetate 225.84mg and 225.8mg and 226mg, or lysine or between 1B 160.08mg and 160.1mg and 160mg, be equivalent or effects equivalent in the present invention, omit to some extent because significant digits are different or accept or reject to some extent; Or, the principal agent component contained in compositions in a unit dose or a unit formulation: L-lysine acetate or between lysine acetate 112.92mg and 112.9mg and 113mg, or between lysine or 1B 80.04mg and 80mg, equivalent or effects equivalent in the present invention, omit to some extent because significant digits are different or accept or reject to some extent, in other compositions of the present invention the significant digits of principal agent or adjuvant accept or reject mode or principle also identical therewith.

For pharmaceutical composition of the present invention, can containing LYS or L-lysine acetate or lysine acetate or lysine or 1B (calculating with anhydride) 80-400mg in compositions in a unit dose or a unit formulation, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate about 85-400mg, this patient according to different indications or crowd or all ages and classes and fixed and aspect manufacture, transport or carry, reduce the expense of manufacturer's time, reduce packing charges or freight or taking convenience at double.LYS (calculating with anhydride) not only containing 100mg in the preparation of a standard unit dosage of the present invention and calcium hydrogen phosphate 2 hydrate of 100mg, and in the preparation of a standard unit dosage, also contain the LYS (calculating with anhydride) of 200mg and calcium hydrogen phosphate 2 hydrate of 200mg, calcium hydrogen phosphate 2 hydrate (calculating with anhydride) of the LYS usually containing 300mg in the preparation of more or one standard unit dosage and 300mg, calcium hydrogen phosphate 2 hydrate (calculating with anhydride) of the LYS usually containing 400mg in the preparation of more or one standard unit dosage and 400mg, the compositions of high unit dose is conducive to obviously reducing the consumption of adjuvant and enhances productivity.

In pharmaceutical composition of the present invention, the type of service of different component can be different, if: LYS or L-lysine acetate or lysine acetate or lysine or 1B can be use its crystalline hydrate (LYS monohydrate, L-lysine acetate trihydrate etc.); Calcium hydrogen phosphate and crystalline hydrate thereof, as calcium hydrogen phosphate 2 hydrate etc., if use its anhydride, its content or inventory can be converted according to calcium hydrogen phosphate 2 hydrate accordingly according to molecular weight; This does not hinder other component use or do not use, when deployed, and can according to chemistry or pharmacy be regular carries out.

In pharmaceutical composition of the present invention, the amount of each component or the pharmaceutically acceptable form of difference (comprising its salt or hydrate) of each component can rationally change or adjust, to form different combinations in the certain limit that the present invention specifies.

The purposes of the compositions of lysine calcium mono hydrogen phosphate of the present invention, is characterized in that: said composition separately or adjuvant acceptable with pharmacy, is preparing the application in tablet, granule, capsule, powder, suspensoid, liquid preparation.

Prevention or treatment 1B and the 1B of calcium deficiency and the preparation method of composition of calcium hydrogen phosphate, get LYS or L-lysine acetate or lysine or 1B and calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate and cross 40 ~ 200 mesh sieves respectively, get the principal agent after sieving, mix homogeneously, survey granule content, granule is prepared in fill capsule or pack.

The compositions of LYS of the present invention or L-lysine acetate or lysine acetate or lysine or 1B and calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate, also can add pharmaceutically acceptable adjuvant and be prepared into pharmaceutical preparation, comprise capsule, tablet (ordinary tablet, dispersible tablet, effervescent tablet, oral cavity disintegration tablet etc.), granule, powder, suspensoid etc.; Its preparation method for by LYS, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate and pharmaceutically acceptable adjuvant be prepared from accordance with the law.Wherein, pharmaceutically acceptable adjuvant comprises filler, lactose, starch, microcrystalline Cellulose, disintegrating agent as hydroxypropyl starch, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, melon you natural gum, methylcellulose one or several, lubricant as magnesium stearate, zinc stearate, micropowder silica gel, Pulvis Talci, Macrogol 2000-8000 one or several, pharmaceutically acceptable correctives and or coloring agent (as aspartame, cyclamate, saccharin sodium, sucralose, sweetleaf centautin, xylitol, sorbitol, xylose, lactose, glycyrrhizin, sucrose, citrus seed oil, oleum Citri sinensis, Fructus Citri Limoniae oil, Oleum menthae, linalool, menthol, curcumin, monascorubin, beet red, amaranth, Xylene Red, sunset yellow, Gardenia Yellow, chlorophyll, red or the food coloring flavochrome of food coloring, other sweeting agent or other essence or other pigment etc.), or pharmaceutically acceptable antiseptic or antifungus agent or antibacterial (benzoic acid or its sodium or potassium salt, sorbic acid or its pharmaceutical salts, potassium sorbate or sodium sorbate, Nipagin ester etc.) etc. in one or more.

The preparation method of solid preparation comprises, supplementary material is crossed 60 ~ 200 mesh sieves respectively, LYS after sieving or L-lysine acetate or lysine acetate or lysine or 1B and calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate and adjuvant are mixed homogeneously, soft material is made with 5-10% binding agent, cross 14 ~ 40 mesh sieves to granulate, 40 ~ 80 DEG C of dryings, cross 14 ~ 40 mesh sieve granulate, with disintegrating agent and magnesium stearate lubricant, zinc stearate, micropowder silica gel, Pulvis Talci, one or several of Macrogol 2000-8000 (add pharmaceutically acceptable suspending agent or stabilizing agent when preparing suspensoid, as xanthan gum, tartaric acid, citric acid, tragakanta, gelatin, fructose, polyvinylpyrrolidone, methylcellulose, ethyl cellulose, sodium carboxymethyl cellulose, sodium alginate, carboxymethyl starch sodium, one or several mix homogeneously in pectin etc., survey granule content, in Filling bag), tabletting or encapsulated, packaging, inspection, obtain finished product.

The compositions of the LYS of a unit dose of the present invention or L-lysine acetate or lysine acetate or lysine or 1B and calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate with same unit dose lysine hydrochloride compared with the compositions of calcium hydrogen phosphate 2 hydrate, what medicine of the present invention can get rid of a half-value dose under similar circumstances is not easily immediately used by the body D-lysine hydrochloride, this means when same quality, the L-type lysine that medicine of the present invention not only can provide the human body first of a multiple dose to lack more, also eliminate the D type isomer that second half can not be absorbed by body, and improve the efficiency etc. of transport calcium ion etc.

Therefore, the present invention not only not only itself provides more lysine of L configuration utilized for human body in the preparation of a unit dose, also contribute to improving on the original basis calcium absorption and by the utilization rate of body, produce better synergy.This also makes the patient for calcium deficiency, for sufferers of osteoporosis face, in same situation, will obtain better effect of supplemented calcium.Being multiplied of L-type lysine in this unit dose, the patient to a certain extent for cerebrovascular disease also has positive effect.

In the process of production unit dosage particles, under square one, contribute to producing exponentially the high preparation of LYS in unit dose formulations or L-lysine acetate or 1B content or compositions within the unit interval, reduce production cost and cost of transportation etc. significantly.

Therefore, for the compositions of relative fixed dosage, no matter the calcium preparation of the 1B containing more is the child and adult that lack for calcium and 1B, or positive meaning is had more for the calcium 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 the construction of environmentally friendly society.

We find, the pH value of the principal agent compositions of different L-lysine acetate of the present invention or lysine acetate and calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate is [under room temperature, about 20-25 DEG C, Example 16 respectively, embodiment 17, embodiment 18, embodiment 19, embodiment 20, embodiment 21, evenly mixed about 4 grams, the powder of mistake 100 mesh sieve of two principal agent components of the shown ratio of embodiment 42 is placed in 50ml flask respectively, add 20ml water for injection, abundant stirring or after jolting 20 minutes, test the pH value of its liquid, find that its pH value is all greater than 6.7] than the pH value of the lysine hydrochloride of prior art and the compositions of calcium hydrogen phosphate 2 hydrate [under room temperature, about 20-25 DEG C, took respectively 100 mesh sieves etc. heavy lysine hydrochloride and calcium hydrogen phosphate 2 hydrate, evenly after mixed powder, get about 4 grams in the 50ml flask of 20ml water for injection, abundant stirring or after jolting 20 minutes, test the pH value of its liquid, find that its pH value is less than 5.9] closer to Human Physiology neutral value, thus better or advantageously, more useful to body.In addition, particularly to acidosic patient, the concentration increasing chloride ion in body again can make the exacerbation of symptoms of metabolic acidosis, for the patient of the renal failure of light moderate, lysine or 1B or L-lysine acetate or lysine acetate more valuable or better safety than lysine hydrochloride.Thus, the compositions of LYS of the present invention or lysine or 1B or L-lysine acetate or lysine acetate and calcium hydrogen phosphate or calcium hydrogen phosphate 2 gas hydrate synthesis has more reality and Long Significance or clinical value, is preventing in potential untoward reaction especially.

In drug use process, untoward reaction is perhaps rare or even rare, and what have is comparatively large to patient effect, although its curative effect of many medicines is obvious, but at home and abroad quits listing because of untoward reaction, such as rosiglitazone, nimesulide, Thalidomide etc.The improvement of medicine is usually careless middle progressive, and ironically, after removing the large S-configuration Thalidomide isomer of side effect in the Thalidomide in racemization, R-Thalidomide is but recaptured newborn.Antihypertensive drug amlodipine is after removing d-isomer, and the curative effect of Levamlodipine is more outstanding, and untoward reaction is lower, obtains and better evaluate after listing.The untoward reaction of medicine is also medicament research and development and evaluates with the key problem must paid close attention to all the time in clinical practice.

For lysine calcium mono hydrogen phosphate composition of medicine involved in the present invention, we find, 68 years old age, height is about 1.58m, the elderly woman that body weight is about 58kg takes lysine hydrochloride calcium hydrogen phosphate tablet (100mg/100mg/ sheet, with lysine hydrochloride and calcium hydrogen phosphate 2 hydrated basis), each 5, twice daily, before taking medicine, be measured as 139/90mmHg in the morning about 8, after taking three weeks continuously, measurement morning about 8, finds that blood pressure rises to 142/92mmHg, surmounts marginal value, patient is slightly dizzy, conscious slightly uncomfortable; Do not take other antihypertensive drugs, drug withdrawal is measurement morning about 8 two days later, and blood pressure is reduced to 140/91mmHg; Then change and take acetic acid 1B calcium hydrogen phosphate particle (about 565mg/500mg/ bag of the present invention, respectively with acetic acid 1B and calcium hydrogen phosphate 2 hydrated basis, two components cross the blend compositions of 100 mesh sieves), each 1 bag, twice daily, after taking three weeks continuously, blood pressure about 8 measurements in continuous two day morning remain on 137/88mmHg, and patient's dizziness disappears.This fully shows advantage of the present invention.

The invention provides improvement or more advantageous lysine and calcium hydrogen phosphate pharmaceutical composition, the present invention also embodies other advantage simultaneously: the compositions 1, providing the new ratio of the compositions of a LYS and calcium hydrogen phosphate, the 1B providing more Absorbable rod effectively to utilize in a unit dose, contributes to the growth promoter of child etc.; 2, the compositions of the new ratio of the compositions of L-lysine acetate and calcium hydrogen phosphate thing is provided, reduces the incidence rate of hyperchloremia; 3, the compositions of lysine or 1B and calcium hydrogen phosphate is provided, the potential incidence rate that during minimizing clinical administration, hyperchloremia occurs; 4, find containing the lysine of lysine hydrochloride and the compositions of calcium hydrogen phosphate and be unfavorable for the treatment of autism children, to to suffer from infantile autism but need the patient of the pharmaceutical composition of lysine supplement and calcium hydrogen phosphate, there is provided the selection that is safer and more effective or more, perhaps this more current pharmacy or clinical ignore or have no promotion; 5, for the selection acidosic patient occurs or easily occurs providing new, or potential untoward reaction is reduced.6, the compositions of L lysine and calcium hydrogen phosphate is provided, can acidosic incidence rate be reduced with lysine hydrochloride in prior art compared with calcium hydrogen phosphate compositions, 7, in a unit formulation of the preparation of prior art, drug content is very low, only has calcium hydrogen phosphate 2 hydrate of lysine hydrochloride containing 100mg and 100mg, and oral dose exceedes usually or need to exceed above dosage, inconvenience is brought to taking medicine, pressure is brought to the manufacturing, particularly when equipment capacity is certain, cause supplying obstacle, again to the packaging having more one or several times, pressure is brought to environment, the invention provides the preparation of the compositions of high unit dose, give and manufacture the drug release one times of equal daily dose or the production capacity of several times and make environment become friendly.8, the 1B of the present invention's acquisition and the compositions of calcium hydrogen phosphate, the lysine hydrochloride of the racemization that the compositions sheet of the LYS that preparation specification is identical or L-lysine acetate calcium hydrogen phosphate is more identical than preparation specification and the compositions of calcium hydrogen phosphate more easily enter blood circulation fast and reach effectively treats concentration, has comparatively significantly clinical advantage.

Get the compositions of lysine calcium mono hydrogen phosphate of the present invention in plastic bottle sealing (sample that in by specific embodiment prepared by each embodiment method), be placed in that temperature is 30 DEG C ± 2 DEG C, relative humidity is test 6 months under 75% ± 5% condition, to take a sample to check 0,6 the end of month quality respectively at test.Detection method of content list of references (document: lysine calcium mono hydrogen phosphate sheet, the national standard WS-10001-(HD-0388)-2002 of calcium hydrogen phosphate, calcium hydrogen phosphate 2 hydrate and 1B; The national standard of lysine calcium mono hydrogen phosphate granule, WS-10001-(HD-0389)-2002), wherein the content of L-lysine acetate or lysine acetate or lysine or 1B or LYS carries out blank determination with L-lysine acetate or lysine acetate or lysine or 1B or LYS reference substance respectively, convert according to its stoichiometry, need capsule shell to remove in capsule during the mensuration of principal agent, the method for the fine powder of its content with reference to tablet or granule national standard is measured.Experiment finds, with the seal-packed LYS of the present invention of plastic bottle or L-lysine acetate or lysine acetate or lysine or 1B and calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate compositions capsule or tablet or granule (each embodiment sample) (in each embodiment, the inventory of each component is labelled amount), measure the sample through accelerated test 0 month and 6 months, find that its character, content etc. have no significant change, meet convention or the regulation of standards of pharmacopoeia.The results are shown in Table 1.

The compositions of LYS of the present invention or L-lysine acetate or lysine acetate or lysine or 1B and calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate, be applicable to supplement for the preparation of prevention and therapy people and mammiferous retarded growth, teenager, anemia of pregnant woman, old man, the calcareous of calcium deficiency patient, or the patient that lacks of 1B supplements the application in the medicine of 1B, metabolic acidosis, cerebral trauma, adjustment blood pressure and osteoporosis etc. or health food.

Consumption usage: generally, with the cubage dosage of calcium, daily requirement amount is come into being ~ 3 years old 200 ~ 800mg, 4 ~ 6 years old 400 ~ 800mg, 7 ~ 10 years old 400 ~ 800mg, adult 400 ~ 1200mg, wet nurse 400 ~ 1200mg (all referring to element calcium above).

Detailed description of the invention

During except there being instruction in an embodiment and separately, in description and claims, all numerical value used should be understood to be in all examples and modify with term " about ", therefore, unless the contrary indication, numerical parameter given in this description and appending claims is approximation, it can change according to by character required for sought by present disclosure, at least, and not the application being intended to limit doctrine of equivalents right, each numerical parameter should consider that the number of significant digits and the routine method of rounding up are explained.

Although numerical range and the parameter of the wide region of setting disclosure are approximations.But numerical value given in a particular embodiment is as far as possible accurately reported, any number comprises some error certainly led to by the standard deviation found in their respective tests in essence.

Unless it is pointed out that in literary composition and illustrated in addition clearly, the singulative " " used in this specification and the appended claims, " one " and " being somebody's turn to do " comprise the plural form referring to thing, so, such as.If comprise the mixture of two or more compounds when mentioning the compositions containing " a kind of compound ", unless it should be noted that in addition and illustrate in addition clearly herein, term "or" generally includes "and/or".

Drug content in each embodiment can be all qualified specification according to the 85-115% of the 90-110% of its labelled amount or labelled amount.

" pharmaceutical composition " used herein refers to the compositions of medicine, and described pharmaceutical composition can contain the pharmaceutically acceptable carrier of at least one.

" pharmaceutically acceptable excipient " used herein refers to the pharmaceutical carrier or solvent that are applicable to the compound administration occasionally provided herein, and it comprises any examples of such carriers that well known to a person skilled in the art and be applicable to specific administration mode,

In order to understand the present invention further, below in conjunction with embodiment, the preferred embodiment of the invention is described, but should be appreciated that these describe just for further illustrating the features and advantages of the present invention, instead of limiting to the claimed invention.

Preparation (the specification: 100mg/100mg grain of embodiment 1 LYS calcium hydrogen phosphate capsule, with LYS and calcium hydrogen phosphate 2 hydrated basis) prescription: LYS 100g, calcium hydrogen phosphate 2 hydrate 100g get recipe quantity, respectively cross 60 ~ 100 mesh sieves, get the LYS after sieving and calcium hydrogen phosphate 2 hydrate, mix homogeneously, survey the content of principal agent in granule, according to dosage fill capsule, packaging, inspection, obtain finished product.

Preparation (specification: 195mg/ grain, respectively with LYS and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 2 LYS calcium hydrogen phosphate capsule: LYS 95g, calcium hydrogen phosphate 2 hydrate 100g; Preparation technology: get recipe quantity, cross the LYS after 60 ~ 100 mesh sieves and calcium hydrogen phosphate 2 hydrate respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage encapsulated, packaging, inspection, to obtain final product.

Preparation (specification: 90mg/100mg/ grain, respectively with LYS and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 3 LYS calcium hydrogen phosphate capsule: LYS 90g, calcium hydrogen phosphate 2 hydrate 100g; Preparation technology: get the LYS after 60 ~ 100 mesh sieves of mistake respectively of recipe quantity and calcium hydrogen phosphate 2 hydrate, mix homogeneously, surveys the content of principal agent in granule, according to dosage fill capsule, and packaging, inspection, obtain finished product.

Preparation (specification: 90mg/110mg/ grain, respectively with LYS and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 4 LYS calcium hydrogen phosphate capsule: LYS 90g, calcium hydrogen phosphate 2 hydrate 110g, magnesium stearate 1g; Preparation technology: get recipe quantity, cross 60 ~ 100 mesh sieves respectively, get the LYS after sieving, calcium hydrogen phosphate 2 hydrate, magnesium stearate, mix homogeneously, survey the content of principal agent in granule, according to dosage fill capsule, packaging, inspection, obtain finished product.

Preparation (specification: 110mg/90mg/ grain, respectively with LYS and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 5 LYS calcium hydrogen phosphate capsule: LYS 110g, calcium hydrogen phosphate 2 hydrate 90g, magnesium stearate 1g; Preparation technology: get LYS, calcium hydrogen phosphate 2 hydrate, the magnesium stearate after 60 ~ 100 mesh sieves of mistake respectively of recipe quantity, mix homogeneously, surveys the content of principal agent in granule, according to dosage fill capsule, and packaging, inspection, obtain finished product.

Preparation prescription (the specification: 112.9mg/100mg/ grain of embodiment 6 L-lysine acetate calcium hydrogen phosphate capsule, respectively with L-lysine acetate and calcium hydrogen phosphate 2 hydrated basis), prescription: L-lysine acetate 112.9g, calcium hydrogen phosphate 2 hydrate 100g; Preparation technology: get recipe quantity, cross the L-lysine acetate after 40 ~ 60 mesh sieves and calcium hydrogen phosphate 2 hydrate respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage fill capsule, packaging, inspection, obtain finished product.

Preparation (specification: L-lysine acetate 113mg/95mg/ calcium hydrogen phosphate 2 hydrates/grain, with L-lysine acetate and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 7 L-lysine acetate calcium hydrogen phosphate capsule: L-lysine acetate 113g, calcium hydrogen phosphate 2 hydrate 95g; Preparation technology: get recipe quantity, cross 60 mesh sieves respectively, get the L-lysine acetate after sieving and calcium hydrogen phosphate 2 hydrate, mix homogeneously, survey the content of principal agent in granule, according to dosage fill capsule, packaging, inspection, obtain finished product.

Preparation (specification: lysine 80mg/100mg/ calcium hydrogen phosphate 2 hydrates/grain, with lysine and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 8 lysine calcium mono hydrogen phosphate capsule: lysine 80g, calcium hydrogen phosphate 2 hydrate 100g; Preparation technology: get recipe quantity, cross the lysine after 60 mesh sieves and calcium hydrogen phosphate 2 hydrate respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage fill capsule, packaging, inspection, obtain finished product.

Preparation (specification: 1B 68mg/90mg/ calcium hydrogen phosphate 2 hydrates/grain, respectively with 1B and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 9 1B calcium hydrogen phosphate capsule: 1B 68g, calcium hydrogen phosphate 2 hydrate 90g; Preparation technology: get recipe quantity, cross the 1B after 60 mesh sieves and calcium hydrogen phosphate 2 hydrate respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage fill capsule, packaging, inspection, obtain finished product.

Preparation (specification: LYS 100mg/100mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with LYS and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 10 LYS calcium hydrogen phosphate particle agent: LYS 100g, calcium hydrogen phosphate 2 hydrate 100g, sucrose 3000g; Preparation technology: get recipe quantity, cross the LYS after 40 ~ 60 mesh sieves and calcium hydrogen phosphate 2 hydrate, sucrose respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage in Filling bag, sealing, inspection, obtain finished product.

Preparation (specification: LYS 200mg/200mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with LYS and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 11 LYS calcium hydrogen phosphate particle agent: LYS 100g, calcium hydrogen phosphate 2 hydrate 100g, sucrose 2000g, xylitol 100g; Preparation technology: get recipe quantity, cross the LYS after 40 ~ 60 mesh sieves and calcium hydrogen phosphate 2 hydrate, sucrose respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage in Filling bag, sealing, inspection, obtain finished product.

Preparation (specification: LYS 300mg/300mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with LYS and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 12 LYS calcium hydrogen phosphate particle agent: LYS 300g, calcium hydrogen phosphate 2 hydrate 300g, sucrose 20g, xylitol 200g; Preparation technology: get recipe quantity, cross the LYS after 60 mesh sieves and calcium hydrogen phosphate 2 hydrate, sucrose, xylitol respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage in Filling bag, sealing, inspection, obtain finished product.

Preparation (specification: LYS 400mg/400mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with LYS and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 13 LYS calcium hydrogen phosphate particle agent: LYS 500g, calcium hydrogen phosphate 2 hydrate 500g, sucrose 10g, xylitol 200g; Preparation technology: get recipe quantity, cross the LYS after 40 ~ 60 mesh sieves and calcium hydrogen phosphate 2 hydrate, sucrose, xylitol respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage in Filling bag, sealing, inspection, obtain finished product.

Preparation (specification: LYS 500mg/500mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with LYS and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 14 LYS calcium hydrogen phosphate particle agent: LYS 500g, calcium hydrogen phosphate 2 hydrate 500g, saccharin sodium 5g, xylitol 100g; Preparation technology: get recipe quantity, cross 40 ~ 60 mesh sieves respectively, get the LYS after sieving and calcium hydrogen phosphate 2 hydrate, saccharin sodium, xylitol, mix homogeneously, survey the content of principal agent in granule, according to dosage divide in pack, sealing, inspection, obtain finished product.

(specification: LYS 600mg/600mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with LYS and calcium hydrogen phosphate 2 hydrated basis in the preparation of embodiment 15 LYS calcium hydrogen phosphate particle agent; Specification: LYS 1200mg/1200mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with LYS and calcium hydrogen phosphate 2 hydrated basis) prescription: LYS 600g, calcium hydrogen phosphate 2 hydrate 600g, sucrose 100g, xylitol 100g; Preparation technology: get recipe quantity, cross the LYS after 60 mesh sieves and calcium hydrogen phosphate 2 hydrate, sucrose, xylitol respectively, mix homogeneously, surveys the content of principal agent in granule, is sub-packed in bag respectively according to different dosage strengths, sealing, inspection, to obtain final product.

Preparation (specification: L-lysine acetate 112.9mg/100mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with L-lysine acetate and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 16 L-lysine acetate calcium hydrogen phosphate particle agent: L-lysine acetate 112.9g, calcium hydrogen phosphate 2 hydrate 100g, sucrose 100g; Preparation technology: get recipe quantity, cross the LYS after 60 mesh sieves and calcium hydrogen phosphate 2 hydrate, sucrose respectively, mix homogeneously, survey the content of principal agent in granule, be according to dosage sub-packed in bag, sealing, inspection, obtain finished product.

Preparation (specification: L-lysine acetate 226mg/200mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with L-lysine acetate and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 17 L-lysine acetate calcium hydrogen phosphate particle agent: L-lysine acetate 226g, calcium hydrogen phosphate 2 hydrate 100g, sucralose 1g, xylitol 200g; Preparation technology: get recipe quantity, cross the L-lysine acetate after 40 ~ 60 mesh sieves and calcium hydrogen phosphate 2 hydrate, sucralose, xylitol respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage divide in pack, sealing, inspection, obtain finished product.

Preparation (specification: L-lysine acetate 339mg/300mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with L-lysine acetate and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 18 L-lysine acetate calcium hydrogen phosphate particle agent: L-lysine acetate 339g, calcium hydrogen phosphate 2 hydrate 300g, sucrose 30g, xylitol 200g; Preparation technology: get recipe quantity, cross the L-lysine acetate after 80 mesh sieves and calcium hydrogen phosphate 2 hydrate, sucrose, xylitol respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage divide in pack, sealing, inspection, obtain corresponding preparation.

(specification: L-lysine acetate 451.6mg/400mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with L-lysine acetate and calcium hydrogen phosphate 2 hydrated basis in the preparation of embodiment 19 L-lysine acetate calcium hydrogen phosphate particle agent; Specification: L-lysine acetate 913.2mg/800mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with L-lysine acetate and calcium hydrogen phosphate 2 hydrated basis) prescription: L-lysine acetate 451.6g, calcium hydrogen phosphate 2 hydrate 400g, sucrose 100g, xylitol 100g; Preparation technology: get recipe quantity, cross the L-lysine acetate after 60 mesh sieves and calcium hydrogen phosphate 2 hydrate, sucrose, xylitol respectively, mix homogeneously, surveys the content of principal agent in granule, is sub-packed in bag respectively according to different dosage strengths, sealing, inspection, obtain corresponding preparation.

Preparation (specification: L-lysine acetate 565mg/500mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with L-lysine acetate and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 20 L-lysine acetate calcium hydrogen phosphate particle agent: L-lysine acetate 565g, calcium hydrogen phosphate 2 hydrate 500g, sucrose 100g, xylitol 100g; Preparation technology: get recipe quantity, cross the L-lysine acetate after 40 ~ 60 mesh sieves and calcium hydrogen phosphate 2 hydrate, sucrose, xylitol respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage divide in pack, sealing, inspection, obtain finished product.

Preparation (specification: L-lysine acetate 678mg/600mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with L-lysine acetate and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 21 L-lysine acetate calcium hydrogen phosphate particle agent: L-lysine acetate 678g, calcium hydrogen phosphate 2 hydrate 600g, sucrose 200g, xylitol 200g; Preparation technology: get recipe quantity, cross 40 ~ 60 mesh sieves respectively, get the L-lysine acetate after sieving and calcium hydrogen phosphate 2 hydrate, sucrose, xylitol, mix homogeneously, survey the content of principal agent in granule, according to dosage divide in pack, sealing, inspection, obtain finished product.

Preparation (specification: 1B 80mg/100mg/ calcium hydrogen phosphate 2 hydrates/bag, with 1B and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 22 1B calcium hydrogen phosphate particle agent: 1B 80g, calcium hydrogen phosphate 2 hydrate 100g; Preparation technology: get recipe quantity, cross the 1B after 60 mesh sieves and calcium hydrogen phosphate 2 hydrate respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage divide in pack, sealing, packaging, inspection, obtain finished product.

Preparation (specification: 1B 160mg/200mg/ calcium hydrogen phosphate 2 hydrates/bag, respectively with 1B and the calcium hydrogen phosphate 2 hydrated basis) prescription of embodiment 23 1B calcium hydrogen phosphate particle agent: 1B 160g, calcium hydrogen phosphate 2 hydrate 200g, sucrose 100g, xylitol 100g; ; Preparation technology: 1B that get recipe quantity, that cross 60 mesh sieves respectively and calcium hydrogen phosphate 2 hydrate, sucrose, xylitol, mix homogeneously, surveys the content of principal agent in granule, according to dosage divides in pack, and sealing, packaging, inspection, obtain finished product.

The preparation prescription of embodiment 24 LYS phosphoric acid hydrogen suspensoid: LYS 100g, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100g, xylitol 500g, xanthan gum 5g; Preparation technology: get recipe quantity, cross the LYS after 80 mesh sieves and calcium hydrogen phosphate 2 hydrate, xylitol, xanthan gum 5g respectively, mix homogeneously, survey the content of principal agent in granule, according to dosage divide in pack, sealing, inspection, obtain finished product.

The preparation (specification: L-lysine acetate 112.9mg/100mg/ calcium hydrogen phosphate 2 hydrates/bag) of embodiment 25 L-lysine acetate phosphoric acid hydrogen suspensoid, prescription: L-lysine acetate 112.9g, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100g, xylitol 500g, xanthan gum 5g; Preparation technology: get recipe quantity, cross the L-lysine acetate after 80 mesh sieves and calcium hydrogen phosphate 2 hydrate, xylitol respectively, and cross the xanthan gum of 100 mesh sieves, mix homogeneously, survey the content of principal agent in granule, according to dosage divide in pack, sealing, inspection, obtain finished product.

Embodiment 26 LYS calcium hydrogen phosphate tablet (100mg/100mg/ sheet, respectively with LYS and calcium hydrogen phosphate 2 hydrated basis) prescription: LYS 100g, calcium hydrogen phosphate 2 hydrate 100g, lactose 50g, microcrystalline Cellulose 300g, replaces hydroxypropyl cellulose 30g, aspartame 1g, micropowder silica gel 5g, the polyvinylpyrrolidone of 5% is appropriate;

Preparation technology: LYS, calcium hydrogen phosphate 2 hydrate, lactose, the microcrystalline Cellulose of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, low-substituted hydroxypropyl cellulose, aspartame mix, polyvinylpyrrolidone (alcohol water of about 80%) solution soft material processed in right amount with 5%, cross 40 mesh sieves to granulate, about 50 DEG C forced air dryings 2 hours, after crossing 40 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Embodiment 27 LYS calcium hydrogen phosphate tablet (200mg/200mg/ sheet, respectively with LYS and calcium hydrogen phosphate 2 hydrated basis) prescription: LYS 200g, calcium hydrogen phosphate 2 hydrate 200g, microcrystalline Cellulose 300g, replacement hydroxypropyl cellulose 30g, micropowder silica gel 5g, the polyvinylpyrrolidone of 5% is appropriate;

Preparation technology: LYS, calcium hydrogen phosphate 2 hydrate, microcrystalline Cellulose, replacement hydroxypropyl cellulose, the micropowder silica gel mix homogeneously of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, polyvinylpyrrolidone (alcohol water of about 80%) solution soft material processed in right amount with 5%, cross 40 mesh sieves to granulate, about 50 DEG C forced air dryings 3 hours, after crossing 24 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Embodiment 28 LYS calcium hydrogen phosphate tablet (specification: 300mg/300mg/ sheet, respectively with LYS and calcium hydrogen phosphate 2 hydrated basis) prescription: LYS 300g, calcium hydrogen phosphate 2 hydrate 200g, starch 50g, microcrystalline Cellulose 200g, low-substituted hydroxypropyl cellulose 30g, micropowder silica gel 8g, 3% hydroxypropyl emthylcellulose is appropriate;

Preparation technology: LYS, calcium hydrogen phosphate 2 hydrate, starch, microcrystalline Cellulose, the low-substituted hydroxypropyl cellulose mix homogeneously of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, with 3% hydroxypropyl emthylcellulose (alcohol water of about 75%) solution soft material processed in right amount, cross 40 mesh sieves to granulate, about 50 DEG C forced air dryings 3 hours, after crossing 30 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 400mg/400mg/ sheet of embodiment 29 LYS calcium hydrogen phosphate tablet, respectively with LYS and calcium hydrogen phosphate 2 hydrated basis) prescription: LYS 400g, calcium hydrogen phosphate 2 hydrate 400g, starch 50g, microcrystalline Cellulose 200, carboxymethyl starch sodium 40g, micropowder silica gel 8g, 3% hydroxypropyl emthylcellulose is appropriate;

Preparation technology: LYS, calcium hydrogen phosphate 2 hydrate, starch, microcrystalline Cellulose, the carboxymethyl starch sodium mix homogeneously of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, with 3% hydroxypropyl emthylcellulose (alcohol water of about 80%) solution soft material processed in right amount, cross 40 mesh sieves to granulate, about 50 DEG C forced air dryings 2 hours, after crossing 40 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 500mg/500mg/ sheet of embodiment 30 LYS calcium hydrogen phosphate tablet, respectively with LYS and calcium hydrogen phosphate 2 hydrated basis) prescription: LYS 500g, calcium hydrogen phosphate 2 hydrate 500g, starch 50g, microcrystalline Cellulose 200, carboxymethyl starch sodium 30g, micropowder silica gel 8g, 3% hydroxypropyl emthylcellulose is appropriate;

Preparation technology: LYS, calcium hydrogen phosphate 2 hydrate, starch, microcrystalline Cellulose, the carboxymethyl starch sodium mix homogeneously of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, with 3% hydroxypropyl emthylcellulose (alcohol water of about 75%) solution soft material processed in right amount, cross 24 mesh sieves to granulate, about 53 DEG C forced air dryings 2 hours, after crossing 20 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 113mg/100mg/ sheet of embodiment 31 L-lysine acetate calcium hydrogen phosphate tablet, respectively with L-lysine acetate and calcium hydrogen phosphate 2 hydrated basis) prescription: L-lysine acetate 113g, calcium hydrogen phosphate 2 hydrate 100g, starch 50g, microcrystalline Cellulose 200g, low-substituted hydroxypropyl cellulose 16g, micropowder silica gel 8g, 4% hydroxypropyl emthylcellulose is appropriate;

Preparation technology: L-lysine acetate, calcium hydrogen phosphate 2 hydrate, starch, microcrystalline Cellulose, the low-substituted hydroxypropyl cellulose mix homogeneously of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, with 4% hydroxypropyl emthylcellulose (alcohol water of about 75%) solution soft material processed in right amount, cross 40 mesh sieves to granulate, about 48 DEG C forced air dryings 3 hours, after crossing 20 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 226mg/200mg/ sheet of embodiment 32 L-lysine acetate calcium hydrogen phosphate tablet, respectively with L-lysine acetate and calcium hydrogen phosphate 2 hydrated basis) prescription: L-lysine acetate 226g, calcium hydrogen phosphate 2 hydrate 200g, starch 50g, microcrystalline Cellulose 200g, low-substituted hydroxypropyl cellulose 30g, micropowder silica gel 8g, the PVP K30 of 5% is appropriate;

Preparation technology: L-lysine acetate, calcium hydrogen phosphate 2 hydrate, starch, the microcrystalline Cellulose of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, low-substituted hydroxypropyl cellulose mix homogeneously, PVP K-30 (alcohol water of about 95%) the solution soft material processed in right amount of 5%, cross 40 mesh sieves to granulate, about 55 DEG C forced air dryings 2 hours, after crossing 20 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 339mg/300mg/ sheet of embodiment 33 L-lysine acetate calcium hydrogen phosphate tablet, respectively with L-lysine acetate and calcium hydrogen phosphate 2 hydrated basis) prescription: L-lysine acetate 339g, calcium hydrogen phosphate 2 hydrate 300g, starch 50g, microcrystalline Cellulose 200g, carboxymethyl starch sodium 30g, micropowder silica gel 8g, 4% hydroxypropyl emthylcellulose is appropriate;

Preparation technology: get after pulverizing respectively and cross the L-lysine acetate of recipe quantity of 100 mesh sieves, calcium hydrogen phosphate 2 hydrate, starch, microcrystalline Cellulose, carboxymethyl starch sodium, micropowder silica gel cross 100 mesh sieves, with 5% hydroxypropyl emthylcellulose (alcohol water of about 75%) solution soft material processed in right amount, cross 40 mesh sieves to granulate, about 50 DEG C forced air dryings 3 hours, after crossing 40 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 451.6mg/400mg/ sheet of embodiment 34 L-lysine acetate calcium hydrogen phosphate tablet, respectively with L-lysine acetate and calcium hydrogen phosphate 2 hydrated basis) prescription: L-lysine acetate 451g, calcium hydrogen phosphate 2 hydrate 400g, starch 50g, microcrystalline Cellulose 200g, low-substituted hydroxypropyl cellulose 30g, micropowder silica gel 8g, the PVP K30 solution of 5% is appropriate;

Preparation technology: L-lysine acetate, calcium hydrogen phosphate 2 hydrate, starch, microcrystalline Cellulose, the low-substituted hydroxypropyl cellulose mix homogeneously of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, PVP K30 (alcohol water of about 90%) solution soft material processed in right amount with 5%, cross 40 mesh sieves to granulate, about 50 DEG C forced air dryings 3 hours, after crossing 24 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 565mg/500mg/ sheet of embodiment 35 L-lysine acetate calcium hydrogen phosphate tablet, respectively with L-lysine acetate and calcium hydrogen phosphate 2 hydrated basis) prescription: L-lysine acetate 565g, calcium hydrogen phosphate 2 hydrate 500g, starch 50g, microcrystalline Cellulose 200g, carboxymethyl starch sodium 30g, micropowder silica gel 8g, the PVP K30 solution of 5% is appropriate;

Preparation technology: L-lysine acetate, calcium hydrogen phosphate 2 hydrate, starch, microcrystalline Cellulose, the carboxymethyl starch sodium mix homogeneously of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, PVP K30 (alcohol water of about 90%) solution soft material processed in right amount with 5%, cross 40 mesh sieves to granulate, about 50 DEG C forced air dryings 3 hours, after crossing 24 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 678mg/600mg/ sheet of embodiment 36 L-lysine acetate calcium hydrogen phosphate tablet, respectively with L-lysine acetate and calcium hydrogen phosphate 2 hydrated basis) prescription: L-lysine acetate 678g, calcium hydrogen phosphate 2 hydrate 600g, starch 50g, microcrystalline Cellulose 200g, low-substituted hydroxypropyl cellulose 30g, micropowder silica gel 8g, 4% hydroxypropyl emthylcellulose is appropriate;

Preparation technology: L-lysine acetate, calcium hydrogen phosphate 2 hydrate, starch, microcrystalline Cellulose, the low-substituted hydroxypropyl cellulose mix homogeneously of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, with 8% hydroxypropyl emthylcellulose (alcohol water of about 75%) solution soft material processed in right amount, cross 40 mesh sieves to granulate, about 50 DEG C forced air dryings 3 hours, after crossing 24 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 80mg/100mg/ sheet of embodiment 37 1B calcium hydrogen phosphate tablet, respectively with 1B and calcium hydrogen phosphate 2 hydrated basis) prescription: 1B 80g, calcium hydrogen phosphate 2 hydrate 100g, starch 50g, microcrystalline Cellulose 200g, low-substituted hydroxypropyl cellulose 30g, micropowder silica gel 8g, the PVP K30 solution of 5% is appropriate;

Preparation technology: 1B, calcium hydrogen phosphate 2 hydrate, starch, microcrystalline Cellulose, the low-substituted hydroxypropyl cellulose mix homogeneously of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, PVP K30 (alcohol water of about 85%) solution soft material processed in right amount with 5%, cross 40 mesh sieves to granulate, about 50 DEG C forced air dryings 3 hours, after crossing 20 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 480mg/600mg/ sheet of embodiment 38 1B calcium hydrogen phosphate tablet, respectively with 1B and calcium hydrogen phosphate 2 hydrated basis) prescription: 1B 480g, calcium hydrogen phosphate 2 hydrate 600g, starch 50g, microcrystalline Cellulose 200g, low-substituted hydroxypropyl cellulose 30g, micropowder silica gel 8g, the PVP K30 solution of 7% is appropriate;

Preparation technology: 1B, calcium hydrogen phosphate 2 hydrate, starch, the microcrystalline Cellulose of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, low-substituted hydroxypropyl cellulose mix homogeneously, PVP K30 (alcohol water of about 90%) solution soft material processed in right amount with 7%, cross 40 mesh sieves to granulate, about 50 DEG C forced air dryings 3 hours, after crossing 24 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

Preparation (the specification: 226mg/200mg/ sheet of embodiment 39 L-lysine acetate calcium hydrogen phosphate tablet, respectively in L-lysine acetate and calcium hydrogen phosphate) prescription: L-lysine acetate 226g, calcium hydrogen phosphate 200g, starch 50g, microcrystalline Cellulose 120g, low-substituted hydroxypropyl cellulose 30g, micropowder silica gel 8g, the PVP K30 of 5% is appropriate;

Preparation technology: L-lysine acetate, calcium hydrogen phosphate, starch, the microcrystalline Cellulose of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, low-substituted hydroxypropyl cellulose mix homogeneously, PVP K-30 (alcohol water of about 95%) the solution soft material processed in right amount of 5%, cross 40 mesh sieves to granulate, about 55 DEG C forced air dryings 2 hours, after crossing 20 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product.

The preparation prescription of embodiment 40 lysine phosphoric acid hydrogen suspensoid: LYS 1200g or L-lysine acetate or lysine acetate 1355.04g or 1355.1g or 1355g or 1356g or lysine or 1B 960.48g or 960.5g or 961g or 960g, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 1200g, xylitol 50g, aspartame 10g, sweetleaf centautin 3g, xanthan gum 20g, tragakanta 2g, methylcellulose 10g, lemon yellow 3g; Preparation technology: get recipe quantity, cross the supplementary material after 100 mesh sieves respectively, mix homogeneously, survey the content of principal agent in granule, be sub-packed in bag according to principal agent calcium hydrogen phosphate 2 hemihydrate content 5000mg or 2400mg or 2000mg or 1200mg or calcium hydrogen phosphate 2 hemihydrate content 1000mg or calcium hydrogen phosphate 2 hemihydrate content 800mg specification, sealing, inspection, obtain the preparation of pharmaceutical compositions different accordingly.

The preparation prescription of embodiment 41 lysine phosphoric acid hydrogen suspensoid: LYS 50g or L-lysine acetate or lysine acetate 56.46g or 56.5g or 57g or 56g or lysine or 1B 40.02g or 40g, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 50g, xylitol 200g, sucralose 1g, xanthan gum 2g; Preparation technology: get recipe quantity, cross the supplementary material after 100 mesh sieves respectively, mix homogeneously, surveys the content of principal agent in granule, is sub-packed in bag according to principal agent calcium hydrogen phosphate 2 hemihydrate content 50mg specification, sealing, inspection, obtain the preparation of pharmaceutical compositions different accordingly.

Preparation (the specification: 226mg/200mg/ sheet of embodiment 42 lysine acetate calcium hydrogen phosphate tablet, respectively with lysine acetate and calcium hydrogen phosphate 2 hydrated basis) prescription: lysine acetate 226g, calcium hydrogen phosphate 2 hydrate 200g, starch 30g, microcrystalline Cellulose 100g, carboxymethyl starch sodium 20g, micropowder silica gel 5g, the PVP K30 of 5% is appropriate;

Preparation technology: lysine acetate, calcium hydrogen phosphate 2 hydrate, starch, the microcrystalline Cellulose of getting the recipe quantity pulverizing afterwards and cross 100 mesh sieves respectively, carboxymethyl starch sodium mix homogeneously, PVP K-30 (alcohol water of about 95%) the solution soft material processed in right amount of 5%, cross 40 mesh sieves to granulate, about 55 DEG C forced air dryings 2 hours, after crossing 20 mesh sieve granulate, mix with the micropowder silica gel of crossing 100 mesh sieves, detect intermediates content, tabletting, packs and get final product

In suitable plastic drug package sealing lucifuge, (in by specific embodiment, each embodiment method prepares each sample to embodiment 43 pharmaceutical composition (getting the preparation of 60 unit dose respectively) of getting 1B calcium hydrogen phosphate of the present invention respectively, with sheet or capsule or bag for minimum dose unit), being placed in temperature is 30 DEG C ± 2 DEG C, relative humidity is carry out 6 months Acceleration study under 75% ± 5% condition to investigate its stability, respectively at test 0, 6 samplings at the end of month detect, find that its character is without obvious change, list of references: lysine calcium mono hydrogen phosphate sheet, national standard WS-10001-(HD-0388)-2002, the national standard of lysine calcium mono hydrogen phosphate granule, the method of WS-10001-(HD-0389)-2002 and Chinese Pharmacopoeia are about the assay method etc. in capsule, find after measured, two principal agent constituent contents have no significant change, the content of two principal agent components, all in the scope of the 90-110% of labelled amount, the results are shown in Table 1.

Table 1 stability test result

The rat administration experiments experiment animal of embodiment 44 compositions: the Wistar rat be born about about 25-28 days 100, ablactation, male and female half and half, body weight, at 68-81 gram, is in a good state of health; Give normal feedstuff to raise, protein content about 16.5%, be divided into five groups according to rat body weight and sex uniform distribution rat, only often organize rat n=20, male and female half and half, make average weight between each group of rat before testing without remarkable significant difference, A group is matched group, gives normal feedstuff; B, C, D, E are experimental group, wherein, B group is compositions group (the principal agent compositions proportioning: 100mg/100mg of lysine hydrochloride calcium hydrogen phosphate, respectively with DL-lysine hydrochloride and each composition weight of calcium hydrogen phosphate 2 hydrated basis), C group is L-lysine acetate calcium hydrogen phosphate compositions group (principal agent compositions proportioning: 226mg/200mg/, with L-lysine acetate and calcium hydrogen phosphate 2 hydrated basis); D group is 1B calcium hydrogen phosphate compositions group (principal agent compositions proportioning: 80mg/90mg/, with 1B and each composition weight of calcium hydrogen phosphate 2 hydrated basis); E is the compositions group (principal agent compositions proportioning: 100mg/100mg, respectively with LYS and each composition weight of calcium hydrogen phosphate 2 hydrated basis) of LYS calcium hydrogen phosphate.B, C, D, E respectively organize and are undertaken feeding after preparation mixes by the compositions of normal feedstuff with each group respectively, and every day, normal feedstuff amount kept impartial, freely drank water and ingested; Wherein, B, C, D, E respectively organize each corresponding compositions respectively phosphoric acid hydrogen calcium 2 hydrate being about the Different Weight ratio of 350mg first week every day and are mixed in normal feedstuff and feed rat, second week rises, B, C, D, E respectively organize every day respectively by be mixed with calcium hydrogen phosphate 2 hydrate be about each corresponding compositions of the Different Weight ratio of 500mg normal feedstuff feed rat.Often organize rat to feed five weeks, claim every rat body weight before experiment, test and claim its body weight to the 5th weekend, then obtain the net gain after five weeks, calculate the average often organized, Analysis of variance, found that each experimental group of C, D, E has significance with the difference of the A group contrasted and B group, its p value ﹤ 0.05; Experimental result is in table 2.

The rat administration experimental result of table 2 pharmaceutical composition

Industrial applicibility etc. and explanation etc. thereof:

Below through the specific embodiment and the embodiment to invention has been detailed description; but should understand; these explanations do not form any restriction to scope of the present invention; person skilled obviously can in the case of without departing from the spirit and scope of protection of the present invention; multiple modification, improvement and replacement and combination can be carried out to technical solutions and their implementation methods of the present invention; realize the technology of the present invention, these are all because falling within the scope of protection of the present invention.Special needs to be pointed out is, be appreciated that the change of a lot of details is possible, all similar replacements and change apparent to those skilled in the art, they are all deemed to be included in spirit of the present invention, scope and content, and the present invention is not limited to above-described embodiment.

Claims

1. the compositions of lysine and calcium hydrogen phosphate, it is characterized in that: containing the principal agent component of following weight ratio in said composition: LYS or its hydrate 85-115 part or L-lysine acetate or lysine acetate or its hydrate 95.98-130 part or 1B or lysine or its hydrate 68.03-92.04 part, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 85-115 part; Calculated weight when wherein the hydrate of LYS or L-lysine acetate or lysine acetate or 1B or lysine is converted into anhydride according to it.

2. the compositions of lysine calcium mono hydrogen phosphate according to claim 1, it is characterized in that: containing the principal agent component of following weight ratio in the said composition of a unit dose or a unit formulation: LYS or its hydrate 85-115 part or L-lysine acetate or lysine acetate or its hydrate 95.98-130 part or 1B or lysine or its hydrate 68.03-92.04 part, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 85-115 part; Or 0.5 ~ 50 times of above-mentioned each principal agent component; The 0.5-50 of the above-mentioned each principal agent component in the different compositions of an above-mentioned unit dose or a unit formulation doubly, can 0.5 be minimum multiple unit, calculate or calculate to increase or calculate according to same ratio and reduce the number of each component, namely 0.5 times, 1 times, 1.5 times, 2 times, 2.5 times, 3 times, 4 times, 5 times, 6 times, 7,8,9,10,12 ..., 25 times; Calculated weight when wherein the hydrate of LYS or L-lysine acetate or lysine acetate or 1B or lysine is converted into anhydride according to it.

3. the compositions of lysine calcium mono hydrogen phosphate according to claim 1, it is characterized in that: the said composition of a unit dose or a unit formulation contains the principal agent component of following weight ratio: LYS 100 parts or L-lysine acetate or lysine acetate 113 parts or 1B or lysine or its hydrate 80 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100 parts, or 0.5 ~ 50 times of above-mentioned each principal agent component.

4. the compositions of lysine calcium mono hydrogen phosphate according to claim 1, it is characterized in that: the said composition of a unit dose or a unit formulation contains the principal agent component of following weight ratio: LYS 110 parts or L-lysine acetate or lysine acetate 130 parts or 1B or lysine or its hydrate 92 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 90 parts, or 0.5 ~ 50 times of above-mentioned each principal agent component.

5. the compositions of lysine calcium mono hydrogen phosphate according to claim 1, it is characterized in that: the said composition of a unit dose or a unit formulation contains the principal agent component of following weight ratio: LYS 90 parts or L-lysine acetate or lysine acetate 96 parts or 1B or lysine or its hydrate 80 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 110 parts, or 0.5 ~ 50 times of above-mentioned each principal agent component.

6. the compositions of lysine calcium mono hydrogen phosphate according to claim 1, it is characterized in that: the said composition of a unit dose or a unit formulation contains the component of following weight ratio: LYS or L-lysine acetate or lysine acetate or 1B or lysine or its hydrate 90 parts, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100 parts, or 0.5 ~ 50 times of above-mentioned each principal agent component.

7. the compositions of lysine calcium mono hydrogen phosphate according to claim 1, it is characterized in that: the principal agent component contained in the compositions in a unit dose or a unit formulation is: LYS 600mg or L-lysine acetate or lysine acetate 677.52mg or 677.5mg or 678mg or lysine or 1B 480.24mg or 480.2mg or 480.3 or 481mg or 480mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 600mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight.

8. the compositions of lysine calcium mono hydrogen phosphate according to claim 1, it is characterized in that: the principal agent component contained in the compositions in a unit dose or a unit formulation is: LYS 500mg or L-lysine acetate or lysine acetate 564.6mg or 565mg or lysine or 1B 400.2mg or 401mg or 400mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 500mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight.

9. the compositions of lysine calcium mono hydrogen phosphate according to claim 1, it is characterized in that: the principal agent component contained in the compositions in a unit dose or a unit formulation is: LYS 400mg or L-lysine acetate or lysine acetate 451.68mg or 451.7mg or 452mg or lysine or 1B 320.16mg or 320.2mg or 320mg or 321mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 400mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight.

10. the compositions of lysine calcium mono hydrogen phosphate according to claim 1, it is characterized in that: the principal agent component contained in the compositions in a unit dose or a unit formulation: LYS 300mg or L-lysine acetate or lysine acetate 338.76mg or 338.8mg or 339mg or lysine or 1B 240.12mg or 240.1mg or 240mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 300mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight.

The compositions of 11. lysine calcium mono hydrogen phosphates according to claim 1, it is characterized in that: the principal agent component contained in the compositions in a unit dose or a unit formulation: LYS 200mg or L-lysine acetate or lysine acetate 225.84mg or 225.8mg or 226mg mg or lysine or 1B 160.08mg or 160.1mg or 160mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 200mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight.

The compositions of 12. lysine Fructus Vitis viniferae calcium hydrogen phosphate according to claim 1, it is characterized in that: the principal agent component contained in the compositions in a unit dose or a unit formulation: LYS 100mg or L-lysine acetate or lysine acetate 112.92mg or 112.9mg or 113mg or lysine or 1B 80.04mg or 80mg, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 100mg, wherein, calculated weight when L-lysine acetate or lysine acetate or lysine or 1B or hydrate are all converted into anhydride according to it, calcium hydrogen phosphate is with calcium hydrogen phosphate 2 hydrate calculated weight.

The compositions of 13. 1Bs according to claim 1 and calcium hydrogen phosphate, it is characterized in that: the said composition of a unit dose or a unit formulation contains the principal agent component of following weight ratio: LYS or its hydrate 85-115 part or L-lysine acetate or its hydrate 95.98-130 part or 1B or its hydrate 68.03-92.04 part, calcium hydrogen phosphate or calcium hydrogen phosphate 2 hydrate 85-115 part, or 0.5 ~ 50 times of above-mentioned each principal agent component, one or more pharmaceutically acceptable adjuvant or excipient also containing 0.0001-5000 part; Wherein, the calculated weight when hydrate of LYS or L-lysine acetate or 1B or lysine is converted into anhydride according to it.

The compositions of 14. lysine calcium mono hydrogen phosphates according to claim 1, it is characterized in that: its purposes is: said composition separately or adjuvant acceptable with pharmacy, is preparing the application in tablet, granule, capsule, powder, suspensoid, liquid preparation.

The compositions of 15. lysine calcium mono hydrogen phosphates according to claim 1, is characterized in that: its purposes is: the application in the health food of preparation prevention or treatment 1B and calcium deficiency, child and adolescent growth dysplasia, osteoporosis, metabolic acidosis, cerebral trauma, adjustment blood pressure and medicine.