CN114767719A - Medicinal composition for preventing and treating rickets and preparation method thereof - Google Patents

Medicinal composition for preventing and treating rickets and preparation method thereof Download PDF

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CN114767719A
CN114767719A CN202210625483.9A CN202210625483A CN114767719A CN 114767719 A CN114767719 A CN 114767719A CN 202210625483 A CN202210625483 A CN 202210625483A CN 114767719 A CN114767719 A CN 114767719A
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vitamin
calcium carbonate
pharmaceutical composition
bacillus coagulans
gelatin
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CN114767719B (en
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王永宏
王朝辉
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Beijing Langdi Pharmaceutical Co ltd
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    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals

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Abstract

The invention relates to a pharmaceutical composition for preventing and treating rickets, which consists of pharmaceutical active ingredients and a pharmaceutically acceptable carrier, wherein the pharmaceutical active ingredients consist of calcium carbonate, vitamin D3, vitamin K2, bacillus coagulans and amino acid, and the content of calcium in the pharmaceutical active ingredients is as follows in terms of calcium element: vitamin D3: vitamin K2: bacillus coagulans: the weight ratio of the amino acid is 250: 0.0025: 0.02-0.04: 15-50: 80-130, the amino acid is selected from any one or the combination of glutamic acid, glutamine, lysine hydrochloride and arginine, and the particle size of the calcium carbonate is less than or equal to 20 um. The invention obviously improves the treatment effect for preventing and treating diseases such as rickets and the like, and obviously improves the stability and the quality uniformity of the preparation.

Description

Medicinal composition for preventing and treating rickets and preparation method thereof
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a medicinal composition for preventing and treating rickets, a preparation method and application thereof.
Background
Rickets are also called vitamin D deficiency rickets, calcium and phosphorus metabolism disorder caused by insufficient vitamin D in bodies of infants, children and teenagers, and vitamin D deficiency enables mature bone to be under calcified, including long epiphyseal end cartilage plates and bone tissues to be under calcified, so that systemic chronic nutritional diseases characterized by skeleton lesion are shown as low-calcium convulsion, growth retardation, cachexia, irritability, easy respiratory tract infection in infancy and the like. The high risk group is infants within 2 years old, and can be prevented by taking sufficient vitamin D. The prevalence rate of northern rickets is higher than that of southern rickets, the prevalence rate of severe rickets is reduced year by year, but the prevalence rate of mild and moderate rickets is still high.
Calcium carbonate D3The tablet is prepared from calcium carbonate and vitamin D3The compound preparation is clinically used for calcium supplement of pregnant and lactating women, climacteric women, old people and children. Calcium is an essential element in maintaining the normal function of the human nervous system, the skeletal muscular system, cell membranes and capillary permeability. Vitamin D3Can promoteThe composition can be used for preventing and treating osteoporosis, rickets, osteomalacia, tetany of infants, rickets with decayed teeth, protecting teeth, facilitating the growth and development of placenta and fetuses of pregnant women, effectively preventing abortion, premature birth, slow development of fetuses and the like, promoting acid-base balance in human serum, reducing electrolyte disorder, improving immunity and resistance, preventing amino acid loss of kidneys, reducing incidence of cancers and the like. But has the disadvantages of low calcium absorption rate and adverse reactions such as constipation and calculus.
Children, especially infants, have unhealthy development of liver and kidney functions, central nervous systems and endocrine systems, are greatly different from adults in the aspects of physiology, pathology, immunity and the like, have obvious difference in pharmacokinetics and pharmacodynamics with adults, and have the characteristics of poor drug tolerance, high incidence rate of adverse drug reactions and the like. The calcium preparation for children is mostly prepared by the way of adult preparation divided dose or suspension prepared by pharmacist. The method causes defects of damage to the structure of the preparation, cross contamination during preparation, poor stability, poor distribution uniformity, interaction between a solvent and a medicament, unstable bioavailability, inaccurate dosage and the like, and thus adverse medication events occur. Therefore, the development of calcium-containing pharmaceutical compositions with diversified dosage and high bioavailability is urgently needed to meet clinical requirements.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition for preventing and treating rickets, which consists of a pharmaceutical active ingredient and a pharmaceutically acceptable carrier, wherein the pharmaceutical active ingredient consists of calcium carbonate, vitamin D3, vitamin K2, bacillus coagulans and amino acid, and the content of calcium in the pharmaceutical active ingredient is as follows in terms of calcium element: vitamin D3: vitamin K2: bacillus coagulans: the weight ratio of the amino acid is 250: 0.0025: 0.02-0.04: 15-50: 80-130, the amino acid is selected from any one or the combination of glutamic acid, glutamine, lysine hydrochloride and arginine, and the particle size of the calcium carbonate is less than or equal to 20 um.
In a preferred embodiment of the present invention, the composition optionally comprises zinc gluconate.
In the preferred technical scheme of the invention, the pharmaceutical active ingredients in the composition consist of calcium carbonate, vitamin D3, vitamin K2, bacillus coagulans, amino acid and zinc gluconate, and the pharmaceutical active ingredients comprise the following calcium elements in percentage by calcium element: vitamin D3: vitamin K2: bacillus coagulans: amino acid (b): the weight ratio of the zinc gluconate is 250: 0.0025: 0.02-0.04: 15-50: 80-130: 15-50, the amino acid is selected from any one or the combination of glutamic acid, glutamine, lysine hydrochloride and arginine, and the particle size of the calcium carbonate is less than or equal to 15 um.
In the preferred technical scheme of the invention, the particle size of the calcium carbonate in the composition is less than or equal to 15um, preferably less than or equal to 10 um.
In the preferred technical scheme of the invention, the viable count of the bacillus coagulans is more than or equal to 5 multiplied by 107CFU/g, preferably ≥ 1X 108CFU/g。
In a preferred technical scheme of the invention, the pharmaceutically acceptable carrier is selected from any one or a combination of gelatin, mannitol, sorbitol, xylitol, carrageenan, pectin, agar, guar gum, arabic gum, konjac gum, xanthan gum, sodium alginate, microcrystalline cellulose, starch, dextrin, povidone, starch slurry, sodium hydroxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, sodium stearyl fumarate, a sweetening agent, essence and a pigment.
In a preferred technical scheme of the invention, the essence is selected from any one of lemon essence, apple essence, strawberry essence, mint essence and orange essence or a combination thereof.
In a preferred technical scheme of the invention, the sweetener is selected from any one of aspartame, glucose, sucrose, sodium cyclamate, lactose, fructose, acesulfame potassium and stevioside or a combination thereof.
In a preferred technical scheme of the invention, the pigment is selected from any one of or a combination of lemon yellow, carmine, erythrosine, beet red, amaranth, indigo, curcumin, carotene, sunset yellow, composite black and fluorescent fruit green.
In the preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition is as follows: vitamin D3: vitamin K2: bacillus coagulans: glutamic acid: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.2: 180: 1250: 5500: 2000: 1500: 100:18.
In the preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition is as follows: vitamin D3: vitamin K2: bacillus coagulans: (ii) glutamine: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.3: 200: 1250: 5500: 2000: 1500: 100:18.
In a preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition: vitamin D3: vitamin K2: bacillus coagulans: lysine hydrochloride: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.4: 300: 1000: 5500: 2000: 1500: 100:18.
In the preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition is as follows: vitamin D3: vitamin K2: bacillus coagulans: arginine: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.4: 300: 1000: 5500: 2000: 1500: 100:18.
In the preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition is as follows: vitamin D3: vitamin K2: bacillus coagulans: zinc gluconate: glutamic acid: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.2: 180: 300: 1250: 5500: 2000: 1500: 100:18.
In a preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition: vitamin D3: vitamin K2: bacillus coagulans: zinc gluconate: glutamine (b): gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.3: 200: 280: 1250: 5500: 2000: 1500: 100:18.
In a preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition: vitamin D3: vitamin K2: bacillus coagulans: zinc gluconate: lysine hydrochloride: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.4: 300: 260: 1000: 5500: 2000: 1500: 100:18.
In a preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition: vitamin D3: vitamin K2: bacillus coagulans: zinc gluconate: arginine: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.4: 300: 350: 1000: 5500: 2000: 1500: 100:18.
The pharmaceutical composition of the invention is prepared according to the conventional preparation method in the field.
Another object of the present invention is to provide a method for preparing a pharmaceutical composition for preventing and treating rickets, wherein the pharmaceutical composition comprises a pharmaceutically active ingredient and a pharmaceutically acceptable carrier, wherein the pharmaceutically active ingredient comprises calcium carbonate, vitamin D3, vitamin K2, bacillus coagulans and amino acid, and the content of calcium in the pharmaceutical active ingredient is as follows: vitamin D3: vitamin K2: bacillus coagulans: the weight ratio of the amino acid is 250: 0.0025: 0.02-0.04: 15-50: 80-130, the amino acid is selected from any one or combination of glutamic acid, glutamine, lysine hydrochloride and arginine, the particle size of the calcium carbonate is less than or equal to 20um, and the method comprises the following steps:
(1) weighing required amounts of vitamin D3 and vitamin K2, stirring, dissolving in 95% ethanol solution, and spraying the obtained ethanol solution of vitamin complex to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) weighing required amount of gelatin, stirring, swelling in required amount of water, stirring, heating to obtain gelatin solution, and keeping the temperature for use;
(3) Weighing the required amount of bacillus coagulans, amino acid and other pharmaceutically acceptable carriers except gelatin, stirring, uniformly mixing with calcium carbonate particles containing vitamin complex, stirring, placing the prepared mixture into a gelatin solution, uniformly mixing, pouring into a mold, and drying under reduced pressure to obtain the calcium carbonate calcium coagulant.
In a preferred embodiment of the present invention, the composition optionally comprises zinc gluconate.
In the preferable technical scheme of the invention, the pharmaceutical active ingredients in the composition consist of calcium carbonate, vitamin D3, vitamin K2, bacillus coagulans, amino acid and zinc gluconate, and the pharmaceutical active ingredients comprise the following calcium elements in percentage by calcium element: vitamin D3: vitamin K2: bacillus coagulans: amino acids: the weight ratio of the zinc gluconate is 250: 0.0025: 0.02-0.04: 15-50: 80-130: 15-50, the amino acid is selected from any one or the combination of glutamic acid, glutamine, lysine hydrochloride and arginine, and the particle size of the calcium carbonate is less than or equal to 15 um.
In a preferred embodiment of the present invention, the preparation method of the composition comprises the following steps:
(1) weighing required amounts of vitamin D3 and vitamin K2, stirring, dissolving in 95% ethanol solution, and spraying the prepared vitamin D complex ethanol solution to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) Weighing required amount of gelatin, stirring, swelling in required amount of water, stirring, heating to obtain gelatin solution, and keeping the temperature for use;
(3) weighing the required amount of bacillus coagulans, zinc gluconate, amino acid and other pharmaceutically acceptable carriers except gelatin, stirring, uniformly mixing with calcium carbonate particles containing multivitamins, stirring, placing the prepared mixture into a gelatin solution, uniformly mixing, pouring into a mold, and drying under reduced pressure to obtain the calcium carbonate calcium complex.
In the preferred technical scheme of the invention, the particle size of the calcium carbonate in the composition is less than or equal to 15um, preferably less than or equal to 10 um.
In the preferred technical scheme of the invention, the viable count of the bacillus coagulans is more than or equal to 5 multiplied by 107CFU/g, preferably ≥ 1X 108CFU/g。
In a preferred technical scheme of the invention, the pharmaceutically acceptable carrier is any one or a combination of gelatin, mannitol, sorbitol, xylitol, carrageenan, pectin, agar, guar gum, arabic gum, konjac gum, xanthan gum, sodium alginate, microcrystalline cellulose, starch, dextrin, povidone, starch slurry, sodium hydroxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, sodium stearyl fumarate, a sweetening agent, essence and a pigment.
In a preferred technical scheme of the invention, the essence is any one or combination of lemon essence, apple essence, strawberry essence, mint essence and orange essence.
In a preferred technical scheme of the invention, the sweetener is selected from any one of aspartame, glucose, sucrose, sodium cyclamate, lactose, fructose, acesulfame potassium and stevioside or a combination thereof.
In a preferred technical scheme of the invention, the pigment is selected from any one of lemon yellow, carmine, erythrosine, beet red, amaranth, indigo, curcumin, carotene, sunset yellow, composite black and fluorescent fruit green or a combination thereof.
In the preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition is as follows: vitamin D3: vitamin K2: bacillus coagulans: glutamic acid: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.2: 180: 1250: 5500: 2000: 1500: 100:18.
In a preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition: vitamin D3: vitamin K2: bacillus coagulans: glutamine (b): gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.3: 200: 1250: 5500: 2000: 1500: 100:18.
In the preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition is as follows: vitamin D3: vitamin K2: bacillus coagulans: lysine hydrochloride: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.4: 300: 1000: 5500: 2000: 1500: 100:18.
In a preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition: vitamin D3: vitamin K2: bacillus coagulans: arginine: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.4: 300: 1000: 5500: 2000: 1500: 100:18.
In the preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition is as follows: vitamin D3: vitamin K2: bacillus coagulans: zinc gluconate: glutamic acid: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.2: 180: 300: 1250: 5500: 2000: 1500: 100:18.
In the preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition is as follows: vitamin D3: vitamin K2: bacillus coagulans: zinc gluconate: glutamine (b): gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.3: 200: 280: 1250: 5500: 2000: 1500: 100:18.
In a preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition: vitamin D3: vitamin K2: bacillus coagulans: zinc gluconate: lysine hydrochloride: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.4: 300: 260: 1000: 5500: 2000: 1500: 100:18.
In the preferred technical scheme of the invention, the calcium carbonate in the pharmaceutical composition is as follows: vitamin D3: vitamin K2: bacillus coagulans: zinc gluconate: arginine: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.4: 300: 350: 1000: 5500: 2000: 1500: 100:18.
In a preferred embodiment of the present invention, the stirring condition is 100rpm to 1000rpm, preferably 200rpm to 800rpm, and more preferably 300rpm to 600 rpm.
In the preferable technical scheme of the invention, the heating temperature is not lower than 45 ℃, preferably not lower than 50 ℃, and more preferably not lower than 60 ℃.
In the preferred technical scheme of the invention, the drying temperature is less than or equal to 60 ℃, preferably less than or equal to 50 ℃, and more preferably less than or equal to 45 ℃.
The invention also aims to provide application of the pharmaceutical composition in preparing a medicament for preventing and treating any one of osteoporosis, rickets and children growth and development disorder or complications thereof.
Another object of the present invention is to provide the use of the pharmaceutical composition of the present invention for the preparation of a calcium-supplemented or calcium-zinc-supplemented preparation.
In a preferred technical scheme, the pharmaceutical composition is used for supplementing calcium or calcium and zinc for the old, children, pregnant women and other people needing calcium supplement.
Unless otherwise indicated, when the present invention relates to percentages between liquids, said percentages are volume/volume percentages; when the invention relates to percentages between liquid and solid, said percentages are volume/weight percentages; the invention relates to the percentages between solid and liquid, said percentages being weight/volume percentages; the balance weight/weight percent.
Compared with the prior art, the invention has the following beneficial effects:
1. the invention scientifically screens the components and the mixture ratio in the pharmaceutical composition, and the components comprise calcium carbonate (the grain diameter is less than or equal to 20 mu m) in the composition and vitamin D3Vitamin K2Zinc gluconate, amino acid, Bacillus coagulans, and vitamin D3Vitamin K2Spraying to calcium carbonate, remarkably improving the stability and quality uniformity of the preparation, and promoting the body to treat calcium, zinc and vitamin D by synergistically utilizing bacillus coagulans and amino acid 3Vitamin K2The absorption and utilization of the composition can improve intestinal flora of patients and inhibit intestinal helicobacter pylori, effectively and durably increase bone density, relieve bone pain, improve bone microstructure, protect bone health, promote bone formation and growth and development, protect teeth and prevent tooth decay, is beneficial to oral health, remarkably improves the treatment effect of the composition for preventing and treating rickets, osteoporosis, children growth and development disorder and other diseases, remarkably improves mouthfeel and gastrointestinal function and flatulence, constipation, calculus and other side reactions, and remarkably improves the safety and effectiveness of the pharmaceutical composition.
2. The preparation method has the advantages of simple and convenient operation, better cost, suitability for industrial production and the like.
Drawings
FIG. 1 shows the effect of the groups tested in test example 1 on the body weight of the rats tested, "-" indicates comparison with the blank control group, P < 0.05, ". DELTA.indicates comparison with the positive control group, P < 0.05.
FIG. 2 Effect of the test groups in test example 1 on bone density in rats tested, "+" indicates comparison with blank control group, P < 0.05, ". DELTA" indicates comparison with positive control group, P < 0.05.
FIG. 3 the effect of the test groups in test example 1 on bone calcium in the test rats, "+" indicates P < 0.05 compared with the blank control group and ". DELTA" indicates P < 0.05 compared with the positive control group.
FIG. 4 Effect of the test groups in test example 1 on the bone weight of the rats, ". X" indicates comparison with the blank control group, P < 0.05, ". DELTA" indicates comparison with the positive control group, P < 0.05.
Detailed Description
The present invention will be specifically described with reference to examples. The embodiments of the present invention are only for illustrating the technical solutions of the present invention, and do not limit the spirit of the present invention.
In the specific embodiment, the bacillus coagulans is commercially available, and the number of viable bacteria is not less than 1000 hundred million cfu/g.
Example 1Preparation of the pharmaceutical composition of the invention
The pharmaceutical composition of the invention comprises the following components in percentage by weight:
Figure BDA0003677130310000111
the preparation of the pharmaceutical composition of the invention comprises the following steps:
(1) weighing required amounts of vitamin D3 and vitamin K2, stirring (300rpm), dissolving in 95% ethanol solution, and spraying the obtained ethanol solution of vitamin complex to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) weighing required amount of gelatin, stirring (500rpm), placing in required amount of water, swelling for 40min, preparing gelatin solution at 55 deg.C and 600rpm, and keeping the temperature for use;
(3) weighing the required amount of bacillus coagulans, glutamic acid, xylitol, mannitol, strawberry essence and aspartame, stirring (600rpm), uniformly mixing with calcium carbonate particles containing compound vitamins, stirring (600rpm), placing the prepared mixture into a gelatin solution, uniformly mixing, pouring into a mold, and drying under reduced pressure (55 ℃), thus obtaining the product.
Example 2Preparation of the pharmaceutical composition of the invention
The pharmaceutical composition of the invention comprises the following components in percentage by weight:
Figure BDA0003677130310000121
the preparation of the pharmaceutical composition of the invention comprises the following steps:
(1) weighing required amounts of vitamin D3 and vitamin K2, stirring (250rpm), dissolving in 95% ethanol solution, and spraying the obtained ethanol solution of vitamin complex to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) weighing required amount of gelatin, stirring (600rpm), placing in required amount of water, swelling for 40min, preparing gelatin solution at 50 deg.C and 600rpm, and keeping the temperature for use;
(3) weighing required amounts of bacillus coagulans, glutamine, xylitol, mannitol, lemon essence and aspartame, stirring (600rpm), uniformly mixing with calcium carbonate particles containing compound vitamins, stirring (600rpm), placing the prepared mixture into a gelatin solution, uniformly mixing, pouring a mold, and drying under reduced pressure (50 ℃), thus obtaining the product.
Example 3Preparation of the pharmaceutical composition of the invention
The pharmaceutical composition comprises the following components in percentage by weight:
Figure BDA0003677130310000131
Figure BDA0003677130310000141
the preparation of the pharmaceutical composition of the invention comprises the following steps:
(1) Weighing required amounts of vitamin D3 and vitamin K2, stirring (300rpm), dissolving in 95% ethanol solution, and spraying the obtained ethanol solution of vitamin complex to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) weighing required amount of gelatin, stirring (500rpm), placing in required amount of water, swelling for 40min, preparing gelatin solution at 55 deg.C and 600rpm, and keeping the temperature for use;
(3) weighing required amounts of bacillus coagulans, lysine hydrochloride, xylitol, mannitol, apple essence and aspartame, stirring (600rpm), uniformly mixing with calcium carbonate particles containing vitamin complex, stirring (600rpm), placing the prepared mixture into a gelatin solution, uniformly mixing, pouring a mold, and drying under reduced pressure (53 ℃), thus obtaining the product.
Example 4Preparation of the pharmaceutical composition of the invention
The pharmaceutical composition comprises the following components in percentage by weight:
Figure BDA0003677130310000142
Figure BDA0003677130310000151
the preparation of the pharmaceutical composition of the invention comprises the following steps:
(1) weighing required amounts of vitamin D3 and vitamin K2, stirring (300rpm), dissolving in 95% ethanol solution, and spraying the obtained vitamin complex ethanol solution to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) Weighing required amount of gelatin, stirring (600rpm), placing in required amount of water, swelling for 40min, preparing gelatin solution at 50 deg.C and 600rpm, and keeping the temperature for use;
(3) weighing the required amount of bacillus coagulans, arginine, xylitol, mannitol, mint essence and aspartame, stirring (600rpm), uniformly mixing with calcium carbonate particles containing compound vitamins, stirring (600rpm), placing the prepared mixture into a gelatin solution, uniformly mixing, pouring into a mold, and drying under reduced pressure (50 ℃), thus obtaining the product.
Example 5Preparation of the pharmaceutical composition of the invention
The pharmaceutical composition comprises the following components in percentage by weight:
Figure BDA0003677130310000152
Figure BDA0003677130310000161
the preparation of the pharmaceutical composition of the invention comprises the following steps:
(1) weighing required amounts of vitamin D3 and vitamin K2, stirring (300rpm), dissolving in 95% ethanol solution, and spraying the obtained ethanol solution of vitamin complex to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) weighing required amount of gelatin, stirring (500rpm), placing in required amount of water, swelling for 40min, preparing gelatin solution at 55 deg.C and 600rpm, and keeping the temperature for use;
(3) Weighing the required amount of bacillus coagulans, zinc gluconate, glutamic acid, xylitol, mannitol, strawberry essence and aspartame, stirring (600rpm), uniformly mixing with calcium carbonate particles containing multivitamins, stirring (600rpm), placing the prepared mixture into a gelatin solution, uniformly mixing, pouring into a mold, and drying under reduced pressure (55 ℃), thus obtaining the product.
Example 6Preparation of the pharmaceutical composition of the invention
The pharmaceutical composition comprises the following components in percentage by weight:
Figure BDA0003677130310000171
the preparation of the pharmaceutical composition of the invention comprises the following steps:
(1) weighing required amounts of vitamin D3 and vitamin K2, stirring (250rpm), dissolving in 95% ethanol solution, and spraying the obtained ethanol solution of vitamin complex to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) weighing required amount of gelatin, stirring (600rpm), placing in required amount of water, swelling for 40min, preparing gelatin solution at 55 deg.C and 600rpm, and keeping the temperature for use;
(3) weighing the required amount of bacillus coagulans, glutamine, zinc gluconate, xylitol, mannitol, lemon essence and aspartame, stirring (600rpm), uniformly mixing with calcium carbonate particles containing multivitamins, stirring (600rpm), placing the prepared mixture into a gelatin solution, uniformly mixing, pouring into a mold, and drying under reduced pressure (50 ℃), thus obtaining the product.
Example 7Preparation of the pharmaceutical composition of the invention
The pharmaceutical composition comprises the following components in percentage by weight:
Figure BDA0003677130310000181
the preparation of the pharmaceutical composition of the invention comprises the following steps:
(1) weighing required amounts of vitamin D3 and vitamin K2, stirring (300rpm), dissolving in 95% ethanol solution, and spraying the obtained vitamin complex ethanol solution to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) weighing required amount of gelatin, stirring (500rpm), placing in required amount of water, swelling for 40min, preparing gelatin solution at 55 deg.C and 600rpm, and keeping the temperature for use;
(3) weighing the required amount of bacillus coagulans, lysine hydrochloride, zinc gluconate, xylitol, mannitol, apple essence and aspartame, stirring (600rpm), uniformly mixing with calcium carbonate particles containing multivitamins, stirring (600rpm), placing the prepared mixture into a gelatin solution, uniformly mixing, pouring into a mold, and drying under reduced pressure (58 ℃), thus obtaining the product.
Example 8Preparation of the pharmaceutical composition of the invention
The pharmaceutical composition comprises the following components in percentage by weight:
Figure BDA0003677130310000191
the preparation of the pharmaceutical composition of the invention comprises the following steps:
(1) Weighing required amounts of vitamin D3 and vitamin K2, stirring (300rpm), dissolving in 95% ethanol solution, and spraying the obtained vitamin complex ethanol solution to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) weighing required amount of gelatin, stirring (600rpm), placing in required amount of water, swelling for 40min, preparing gelatin solution at 55 deg.C and 600rpm, and keeping the temperature for use;
(3) weighing the required amount of bacillus coagulans, zinc gluconate, arginine, xylitol, mannitol, mint essence and aspartame, stirring (600rpm), uniformly mixing with calcium carbonate particles containing multivitamins, stirring (600rpm), placing the prepared mixture into a gelatin solution, uniformly mixing, pouring into a mold, and drying under reduced pressure (50 ℃), thus obtaining the product.
Test example 1The influence of the pharmaceutical composition on the bone mineral density and the bone weight of the rat to be tested
SPF grade female weaning SD rats were selected at 50. During the test, the test animals freely ingest and drink deionized water at room temperature of 20-24 ℃ and relative humidity of 55-68%. After one week of adaptive feeding, the rats were randomly divided into five groups, a blank control group (gavage pure water), a positive control group (calcium carbonate D3 granules produced by gavage Beijing, Shadongtongrandi pharmaceutical Co., Ltd., in a dosage of 240mg/kg.bw in terms of calcium), a group I (the pharmaceutical composition of gavage example 3 in a dosage of 240mg/kg.bw in terms of calcium), a group II (the pharmaceutical composition of gavage example 5 in a dosage of 240mg/kg.bw in terms of calcium), a group III (the pharmaceutical composition of gavage example 7 in a dosage of 240mg/kg.bw in terms of calcium), and 10 rats each group. The test animals were gavaged 10mL/kg.bw daily, once daily. Weigh the body weight weekly. After continuous gavage for 12 weeks, the animals were sacrificed under anesthesia, the femurs on both sides of the test animals were removed, they were placed in an oven at 105 ℃ to dry to a constant weight, and the right femurs were weighed. And detecting the calcium content of the right femur by adopting an atomic absorption spectrophotometer method. And detecting the bone density of the left femur by adopting a full-automatic high-resolution X-ray machine. The results are shown in FIGS. 1-4.
The above description of the embodiments of the present invention is not intended to limit the present invention, and those skilled in the art may make various changes and modifications without departing from the spirit of the present invention, which should fall within the scope of the appended claims.

Claims (10)

1. A pharmaceutical composition for preventing and treating rickets, which is characterized by comprising a pharmaceutical active ingredient and a pharmaceutically acceptable carrier, wherein the pharmaceutical active ingredient comprises calcium carbonate, vitamin D3, vitamin K2, Bacillus coagulans and amino acid, and the content of calcium in the pharmaceutical active ingredient is as follows in terms of calcium element: vitamin D3: vitamin K2: bacillus coagulans: the weight ratio of amino acid is 250: 0.0025: 0.02-0.04: 15-50: 80-130, the amino acid is selected from any one or combination of glutamic acid, glutamine, lysine hydrochloride and arginine, and the particle size of the calcium carbonate is less than or equal to 20 um.
2. The pharmaceutical composition according to claim 1, wherein the calcium carbonate in the composition has a particle size of 15um or less, preferably 10um or less.
3. The pharmaceutical composition of any one of claims 1-2, wherein the bacillus coagulans has a viable count of 5 x 10 or more 7CFU/g, preferably ≥ 1X 108CFU/g。
4. A pharmaceutical composition according to any one of claims 1 to 3, wherein the pharmaceutically acceptable carrier is selected from any one of gelatin, mannitol, sorbitol, xylitol, carrageenan, pectin, agar, guar gum, gum arabic, konjac gum, xanthan gum, sodium alginate, microcrystalline cellulose, starch, dextrin, povidone, starch slurry, sodium hydroxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, sodium stearyl fumarate, sweeteners, flavours, colours or combinations thereof.
5. The pharmaceutical composition of any one of claims 1-4, wherein the calcium carbonate: vitamin D3: vitamin K2: bacillus coagulans: lysine hydrochloride: gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.4: 300: 1000: 5500: 2000: 1500: 100:18.
6. The pharmaceutical composition of any one of claims 1-4, wherein the calcium carbonate: vitamin D3: vitamin K2: bacillus coagulans: glutamine (b): gelatin: xylitol: mannitol: essence: the mass ratio of aspartame is 6250: 0.025: 0.3: 200: 1250: 5500: 2000: 1500: 100:18.
7. The method of preparing a pharmaceutical composition according to any one of claims 1 to 6, wherein the composition comprises a pharmaceutically active ingredient and a pharmaceutically acceptable carrier, wherein the pharmaceutically active ingredient comprises calcium carbonate, vitamin D3, vitamin K2, Bacillus coagulans and an amino acid, and the ratio of calcium in the pharmaceutically active ingredient is as follows, calculated as calcium: vitamin D3: vitamin K2: bacillus coagulans: the weight ratio of the amino acid is 250: 0.0025: 0.02-0.04: 15-50: 80-130, the amino acid is selected from any one or combination of glutamic acid, glutamine, lysine hydrochloride and arginine, the particle size of the calcium carbonate is less than or equal to 20um, and the method comprises the following steps:
(1) weighing required amounts of vitamin D3 and vitamin K2, stirring, dissolving in 95% ethanol solution, and spraying the obtained ethanol solution of vitamin complex to calcium carbonate to obtain calcium carbonate containing vitamin complex;
(2) weighing required amount of gelatin, stirring, swelling in required amount of water, heating, stirring to obtain gelatin solution, and keeping the temperature for use;
(3) weighing the required amount of bacillus coagulans, amino acid and other pharmaceutically acceptable carriers except gelatin, stirring, uniformly mixing with calcium carbonate containing vitamin complex, stirring, placing the prepared mixture into gelatin solution, uniformly mixing, pouring into a mold, and drying under reduced pressure to obtain the product.
8. The method of claim 7, wherein the stirring conditions are 100rpm to 1000rpm, preferably 200rpm to 800rpm, more preferably 300rpm to 600 rpm.
9. The method of any one of claims 7-8, wherein the drying temperature is 60 ℃ or less, preferably 50 ℃ or less, more preferably 45 ℃ or less.
10. Use of the pharmaceutical composition according to any one of claims 1 to 6 or the pharmaceutical composition prepared by the method according to any one of claims 7 to 9 for the manufacture of a medicament for the prevention and treatment of rickets, osteoporosis, any one of growth and development disorders in children or complications thereof.
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