Amino-acid metal chelate and preparation thereof and preparation method
The present invention relates to amino-acid metal chelate and preparation thereof and preparation method.
Calcium is one of important element that constitutes human body, and calcium has important function to system's normal physiological functions such as circulation, breathing, muscle, skeleton and immunity of keeping human body.Some minor metallic elements outside the deliming such as magnesium, ferrum, zinc, copper, manganese and selenium etc. are in systemic growth and keep in the adjusting of physiological process and also play important effect.Though all contain calcium or other minor metallic element in food, because various factors has influenced absorption, regular meeting causes human body calcium deficiency or other trace element, for example old man, child, climacteric women or patient.Often because of calcium deficiency produces a series of disease, as rickets of child, senile osteoporosis, dental caries or periodontitis etc.
In order to replenish calcium or other trace element, existing calcium preparation mainly contains two classes on the market: a class is calcium of organic acid such as calcium gluconate, calcium lactate, calcium citrate, C8H12CaN2O8, calcium glycerophosphate and calcium acetate etc.Another kind of is mineral acid calcium such as calcium chloride, calcium hydrogen phosphate, calcium carbonate, calcium oxide (trade name vigor calcium), also has bone meal etc. in addition.But little, the most of absorbance of some dissolubility in water of these calcium preparation is low, other can water-solublely be generated inorganic calcium salt by the dissolved calcium of gastric acid under one's belt in digestive tract, yet these calcium salts are easy to be formed insoluble calcium phosphate by the oxalic acid in the food, phosphoric acid etc., and influence absorbs." vigor calcium " in the above-mentioned calcium preparation, though content is higher, because of wherein Main Ingredients and Appearance calcium oxide is too big to the gastrointestinal stimulation, life-time service is difficulty.For minor metallic element, it must form behind polypeptide or the amino acid whose metallo-chelate in vivo could be through intestinal absorption, is absorbed by cell membrane and the big polypeptide metallo-chelate of molecular weight is difficult.
The objective of the invention is to overcome the weak point of above-mentioned calcium and other Rare Elements Preparations, develop new amino-acid metal chelate, it is absorbed by the body easily.
The invention provides a kind of new amino-acid metal chelate, this chelate is the amino-acid metal chelate that is formed less than 300 aminoacid and divalent metal element by molecular weight.
Another object of the present invention has provided above-mentioned amino-acid metal chelate preparation, said preparation is formed as active ingredient and other pharmaceutical carrier with amino-acid metal chelate, and can form 100% composition with any proportioning that contains medicinal carrier 99.9-0.01% by containing amino-acid metal chelate 0.01-99.9%.
Another purpose of the present invention has provided the preparation method of above-mentioned amino-acid metal chelate preparation.This method comprises the following steps: (1) preparation amino-acid metal chelate:
Metal, metal-oxide or metal hydroxides is soluble in water, the amino acid solution that adds 2 gram-molecular weights, 60-80 ℃ of reactions 2-20 hours, obtain clear solution, PH is 7~8, to make the powdery amino-acid metal chelate after this solution drying again, maybe can be with metal carbonate adding soluble in water Na
2CO
8(measuring 1 mole) room temperature was placed 2 hours, added the amino acid solution of 2 gram-molecular weights, stirred 2-4 hours, and the citric acid that adds 1 gram-molecular weight in solution is stirred to, and PH7-8 filters the back spray drying and makes the powdery amino-acid metal chelate; (2) preparation amino-acid metal chelate preparation:
With the above-mentioned amino-acid metal chelate that makes with make various oral formulations according to a conventional method after pharmaceutical carrier mixes.
Preparation method of the present invention can be represented with following reaction equation 1-3: M represents metal in the formula.
Amino-acid metal chelate preparation of the present invention, wherein said metal M can be magnesium, manganese, ferrum, copper and zinc; Described aminoacid is molecular weight less than 300 aminoacid, can be glycine, arginine, agedoite, aspartic acid, alanine, glutamic acid, glutamine, cysteine, histidine, hydroxyproline, isoleucine, leucine, lysine, tryptophan, proline, serine, phenylalanine, valine, threonine, methionine, ornithine or dipeptides, tripeptides and tetrapeptide etc.; Described pharmaceutical carrier has filler such as ca. phosphate dibasic usp23 two water things, Lactis Anhydrous DTG, lactose beadlet, sorbitol, mannitol, glucose and single alkali calcium phosphate etc. or multiple fructose such as Fructus Crataegi powder etc.; Binding agent can be sugar, and natural polymer (starch, arabic gum etc.), two or more in the synthetic polymer (methylcellulose and polyvinylpyrrolidone etc.) mix arbitrarily to be selected for use; Disintegrating agent comprises starch based, potter's clay class, cellulose family, Sargassum acids, gummy class; Lubricant comprises Metallic stearates, Pulvis Talci, stearic acid, silicone, silicon dioxide, Polyethylene Glycol etc. and medicinal coloring agent of using always and fragrant correctives etc.
Amino-acid chelate preparation of the present invention can be water-soluble, take the back human body the absorbance height, have no side effect, be the more satisfactory additional calcium and the preparation of other minor metallic element, especially more China senile osteoporosis patient, have better therapeutic effect.
Example 1, preparation C8H12CaN2O8
Calcium hydroxide 74.1 grams of 1 gram-molecular weight are dissolved in the 1000ml water, form the calcium hydroxide saturated solution, Aspartic Acid 266 grams that in this solution, add 2 gram-molecular weights, reaction is 4 hours under 80 ℃ of conditions, obtain clear solution, PH is 5.8-6.5, and with reacting liquid filtering, the filtrate drying makes Aspartic Acid calcium powder 30 grams.Calcium content is 12-14%.
Example 2, preparation zinc glutamate
1 gram sodium carbonate is dissolved in the 82.2ml water, then 24.5 gram glutamic acid is dissolved in, and adds 4.4 gram zinc oxide again, obtains clear solution 70 ℃ of reactions after 14 hours, and PH is 8, filters, and makes the glutamic acid zinc powder after filtrate is spray-dried, and zinc content is 10.22%.
Example 3, preparation cupric glycinate
6.1 the gram curpic carbonate adds in the 80.9ml water, add 4.9 gram sodium carbonate again, room temperature was placed 2 hours, added 8.2 gram glycine again, slowly stirred 2 hours, the citric acid that in solution, adds 65 grams 15%, agitating solution 20 hours, PH are 7.5, filter, the spray-dried glycine copper powder that makes of filtrate, copper content 14%.
Example 4: preparation Aspartic Acid calcium tablet
500 gram Fructus Crataegi powder, 10 gram albumen Icing Sugar, 275 gram cane sugar powders mixed 80 mesh sieves with 15 gram magnesium stearate, added Aspartic Acid calcium powder 500 gram mixings then, sieved after drying, granulation, tabletting become 1000.
Example 5, preparation glycine calcium tablet
140 gram glycine calcium powders, 95 gram sodium bicarbonate, 200 gram anhydrous citric acid powder, 541 gram cane sugar powders mix with 24 gram egg albumen powders, 40 mesh sieves, after adding an amount of anhydrous alcohol and kneading, pass through 60 order to 20 mesh sieves respectively, after 16 mesh sieves, drying, pelletizing press sheet.
Example 6, preparation ascorbic acid calcium tablet
150 gram calcium ascorbate, 4.55 gram folic acid, 36.78 gram phosphoric acid verdoflavin sodium, 41.2 gram pyridoxal hydrochlorides, 3.4 gram biotin mix with 133.38 gram calcium pantothenates, cross 20 mesh sieves, obtain the water soluble vitamins powder with 8.51 gram lactose powder mixing, these powder 25 grams are mixed with 18g Aspartic Acid calcium powder, add 32 gram sodium bicarbonate, 60 gram anhydrous citric acid powder again, the 280g cane sugar powder, 8g albumen Icing Sugar.Method is with example 2.
Example 7, preparation Aspartic Acid calcium capsule
Behind the method system calcium powder with example 1, make capsule.Make 30 milligrams of every capsules calcics.
Example 8, preparation Aspartic Acid those high in calcium soda pop
After making calcium powder with the method for example 1, add soda pop and promptly get high calcium soda pop, per 250 milliliters of soda pops add 4 and restrain calcium powders.
Example 9, preparation C8H12CaN2O8 nutritional solution
After making calcium powder with the method for example 1, get 300 gram calcium powders and add 24.2 gram sodium bicarbonate, 2.0 gram sodium pyrosulfite; 0.05g disodium edetate adds to 1000ml and can be made into the oral calcium-supplementing nutritive liquid of energy, calcium content 4 mg/ml.