CN110693901A - Calcium vitamin D chewable tablet and preparation method thereof - Google Patents

Calcium vitamin D chewable tablet and preparation method thereof Download PDF

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Publication number
CN110693901A
CN110693901A CN201911063035.9A CN201911063035A CN110693901A CN 110693901 A CN110693901 A CN 110693901A CN 201911063035 A CN201911063035 A CN 201911063035A CN 110693901 A CN110693901 A CN 110693901A
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calcium
vitamin
parts
fermentation
steps
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李红艳
邓文峰
刘海琼
李思睿
张海玲
符晓霞
王昱翔
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Shanghai Children Nutrition Center (Hainan) Co.,Ltd.
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Shanghai Children Nutrition Center Co Ltd Hainan Branch
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
    • A23L29/37—Sugar alcohols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A23L33/155—Vitamins A or D
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Abstract

The invention provides a calcium vitamin D chewable tablet and a preparation method thereof, wherein the calcium vitamin D chewable tablet comprises the following components in parts by weight: 211.28 portions of calcium hydrophosphate plus or minus 1 percent; 207.22 portions of L-calcium lactate pentahydrate +/-1 percent; vitamin D30.63 part of composite powder +/-1%; 730.35 portions of D-mannitol +/-1 percent; 20.00 parts of citric acid +/-1%; 14.40 parts of magnesium stearate +/-1%; 3.32 parts of povidone K30 +/-1%; 0.80 part of sucralose +/-1 percent; the orange essence accounts for 12.00 parts plus or minus 1 percent. The chewable tablet is suitable for the taste of most people; and the pressed sheet is not sticky and does not crack in the preparation process, and the obtained sheet is smooth.

Description

Calcium vitamin D chewable tablet and preparation method thereof
Technical Field
The invention relates to a medicine or health-care food for supplementing nutrient substances to human bodies, in particular to a calcium vitamin D chewable tablet and a preparation method thereof.
Background
The L-calcium lactate is bio-fermented organic calcium, the absorption rate is higher than that of other calcium supplement products, after entering the intestinal tract, free lactic acid changes the pH value in the intestinal cavity, so that the growth of escherichia coli in the colon is inhibited, the amount of escherichia coli is reduced, blood ammonia is reduced, and the colon calcium supplement product is beneficial to health.
The L-calcium lactate is water-soluble and well-soluble calcium preparation, and compared with various calcium preparations, the solubility of various calcium preparations is L-calcium lactate 1345, DL-calcium lactate 702, calcium carbonate 0.56, calcium gluconate 670, calcium citrate 20, and active calcium (Ca (OH))2)65, amino acid calcium 224.
Calcium carbonate is the most widely used calcium supplement agent in the market, on one hand, calcium carbonate is alkalescent and is dissolved in gastric juice in vivo to release calcium ions, and dyspepsia and abdominal distension can be caused by consuming gastric acid after long-term administration. On the other hand, it is an inorganic compound, in the form of a white solid, odorless, neutral, substantially insoluble in water, with a lower absorption rate than L-calcium lactate.
Despite the advantages of L-calcium lactate, L-calcium lactate itself has a bitter taste, which is not readily acceptable when formulated as a calcium supplement. In addition, the preparation of the L-calcium lactate is usually prepared by a fermentation method, the whole preparation process involves a plurality of substances, the components in the fermented solution are complex, and how to extract the L-calcium lactate which has high purity and meets the requirements of calcium supplement preparations is an important problem; in addition, the crystal size distribution of L-calcium lactate is also an important factor affecting the quality of calcium supplement preparations.
Disclosure of Invention
The invention mainly aims to provide a novel calcium vitamin D chewable tablet which has both taste and calcium supplement performance.
In order to achieve the purpose, the invention provides a calcium vitamin D chewable tablet which comprises the following components in parts by weight: 211.28 portions of calcium hydrophosphate plus or minus 1 percent; 207.22 portions of L-calcium lactate pentahydrate +/-1 percent; vitamin D30.63 part of composite powder +/-1%; 730.35 portions of D-mannitol +/-1 percent; 20.00 parts of citric acid +/-1%; 14.40 parts of magnesium stearate +/-1%; 3.32 parts of povidone K30 +/-1%; 0.80 part of sucralose +/-1 percent; the orange essence accounts for 12.00 parts plus or minus 1 percent.
In a preferable scheme, 211.28 parts of calcium hydrophosphate; 207.22 parts of L-calcium lactate pentahydrate; vitamin D30.63 part of composite powder; 730.35 parts of D-mannitol; 20.00 parts of citric acid; 14.40 parts of magnesium stearate; 3.32 parts of povidone K30; 0.80 part of sucralose; the orange essence accounts for 12.00 parts.
In a preferred embodiment, said per gram of vitamin D is3The composition powder contains sucrose 175mg, sodium ascorbate 40mg, and vitamin D32.5mg of caprylic acid, 30mg of capric acid glyceride, 12mg of silicon dioxide and dl-alpha-tocopherol10mg and sodium starch octenyl succinate 730.5 mg.
The invention provides a preparation method of a calcium vitamin D chewable tablet, which comprises the following steps: s1: weighing and proportioning; s2: granulating; s3: drying; s4: mixing; s5: tabletting; s6: packaging in an inner package; s7: packaging;
one preferred embodiment comprises the following steps:
in S1, vitamin D is weighed3The preparation method comprises the following steps of (1) filling weighed materials into a container or a material bag, sealing, and attaching a material label to the outer layer of the container or the material bag for later use, wherein the materials comprise combined powder, L-calcium lactate pentahydrate, calcium hydrogen phosphate, D-mannitol, citric acid, sweet orange essence, magnesium stearate, sucralose and polyvidone K30;
the following steps are included in S2:
s2-1: preparing adhesive, weighing polyvidone K30, adding purified water, stirring to dissolve uniformly to obtain 2% polyvidone slurry, adding sucralose and vitamin D3Adding the combined powder and citric acid into the povidone slurry, and uniformly stirring for later use;
s2-2: pouring weighed materials of L-calcium lactate pentahydrate, calcium hydrophosphate, D-mannitol and sweet orange essence into a high-efficiency wet mixing granulator, adding a binder to prepare a soft material, and then granulating on a swinging granulator by using a 24-mesh nylon screen;
the following steps are included in S3: drying the prepared wet granules by using an oven at the temperature of 55 +/-5 ℃ until the drying weight loss of the granules meets the requirement, and finishing the granules by using a 24-mesh screen;
the following steps are included in S4: putting the dry granules and the magnesium stearate into a mixer and uniformly mixing;
the following steps are included in S5: tabletting according to the marked weight of 1.2 g/tablet, and checking the appearance and weight of the tablet at regular time;
the following steps are included in S6: performing inner packaging according to the operation rules of the equipment, and clearing the field according to the requirements after the production is finished;
the following steps are included in S7: and (5) packing and boxing the small boxes.
In a preferred embodiment, the preparation method of the L-calcium lactate pentahydrate in step S1 is as follows:
performing Sa strain culture, namely placing rhizopus oryzae in a corn starch pilot tube for slant culture for 7-10 d, inoculating the rhizopus oryzae into a triangular flask, performing seed culture on a shaking table, inoculating the rhizopus oryzae into a seed tank for fermentation culture after 20-24 h, wherein the fermentation culture time is 16-20 h;
preparing an Sb fermentation culture medium, namely preparing starch slurry from corn starch, excessive neutralizer calcium carbonate and alpha-amylase, adding the starch slurry into a fermentation tank, adding nutrient salt and ammonium sulfate, uniformly stirring, introducing 0.1MPa steam into the fermentation tank for sterilization for 20min, and then cooling the culture medium to 34 ℃;
sc fermentation, namely inoculating the strain cultured in the step Sa into a fermentation medium prepared from Sb, introducing sterile compressed air, and culturing for 32-34 h;
sd fermentation liquor treatment, adding active carbon into the fermentation liquor obtained in the step Sc, continuously stirring for decoloring and deodorizing, filtering again, and transferring the filtrate into a crystallizer;
se crystallization, namely adjusting the pH value of the filtrate in the Sd crystallizer to 6.5-7.5, adding ethanol at a constant temperature of 35 ℃, cooling to 5-10 ℃, filtering and separating, and collecting a filter cake;
sf washing the filter cake with ethanol, and drying the filter cake to obtain the L-calcium lactate pentahydrate.
One preferable scheme is that the inoculation amount of rhizopus oryzae in the step Sa is 5-10% v/v, sterile compressed air needs to be introduced into a seeding tank, the ventilation amount is 0.5v/v ∙ min, the temperature of the seeding tank is 34 ℃, and a nitrogen source added into the seeding tank is ammonium sulfate;
in the step Sb, the adding amount of the corn starch is 13% of the total mass of the culture medium, the concentration of the alpha-amylase in the culture medium is 5-10 mu g/g, and the filling amount of the culture medium in a fermentation tank is 70%;
the inoculation amount of the strains in the step Sc accounts for 5-10% of the volume of the culture medium, the ventilation amount of sterile compressed air is 0.5v/v ∙ min, the tank pressure is 0.1MPa and the temperature is 34 ℃ in the fermentation process; a cyclone separator is arranged on an exhaust pipe of the fermentation tank, and feed liquid obtained by separating foam generated in the fermentation process is introduced into the fermentation tank;
the adding amount of the ethanol in the step Se is 3-5 times of the total volume of the fermentation liquor, and the adding mode of the ethanol is as follows: 1/5 of the total amount of ethanol is added at a constant speed within 0-30 min, 2/5 of the total amount of ethanol is added at a constant speed within 30-60 min, and 2/5 of the total amount of ethanol is added at a constant speed within 60-180 min; the cooling mode is that the mixture is stood and naturally cooled to 20 ℃, and then is rapidly cooled to 5-10 ℃ within 5 min;
the drying temperature in the step Sf is 50-55 ℃, the pressure during drying is 0.08-0.09 MPa, and the drying time is 2-3 h.
The invention has the beneficial effects that:
the calcium supplement agent of the product is organic calcium L-calcium lactate, has the levorotatory characteristic, is compatible with the levorotatory physiological characteristic of a human body, and has good solubility. However, L-calcium lactate has bitter taste, the bitter taste is reduced by using a sweetening agent of sucralose, D-mannitol with sweetness and good mouthfeel and citric acid with sour taste, and sweet orange essence is added, so that the L-calcium lactate has light faint scent and is more suitable for the taste of most people. The tablet is not sticky and smooth and does not crack.
The preparation method of the L-calcium lactate pentahydrate is optimized, the crystallization process of the fermentation liquid is optimized, the dissolution method is matched with the cooling crystal phase, and the adding mode and the cooling mode of the dissolution agent are optimized, so that the prepared L-calcium lactate pentahydrate has larger particle size and uniform particle size distribution, the phenomena of tabletting and sticking during the preparation process of the calcium vitamin D chewable tablet are further reduced, and the high quality of the product is ensured by matching with other process condition parameters in the preparation process of the chewable tablet.
Drawings
The present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.
Fig. 1 is a schematic structural diagram of an embodiment of the present invention.
Detailed Description
The technical solution in the embodiments of the present invention is clearly and completely described below with reference to the drawings in the embodiments of the present invention. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.
The first embodiment:
the calcium vitamin D chewable tablet of the embodiment is prepared by the following components in weight ratio.
Figure BDA0002256030320000051
Figure BDA0002256030320000061
Wherein per gram of vitamin D3The composition powder contains sucrose 175mg, sodium ascorbate 40mg, and vitamin D32.5mg, octyl, 30mg of glyceryl decanoate, 12mg of silicon dioxide, 10mg of dl-alpha-tocopherol and 730.5mg of starch sodium octenyl succinate.
The preparation method of the calcium vitamin D chewable tablet provided by the embodiment comprises the following steps: s1: weighing and proportioning; s2: granulating; s3: drying; s4: mixing; s5: tabletting; s6: packaging in an inner package; s7: packaging;
specifically, in S1, vitamin D is weighed3The preparation method comprises the following steps of (1) filling weighed materials into a container or a material bag, sealing, and sticking a material label on the outer layer of the container or the material bag for later use, wherein the materials comprise combined powder, L-calcium lactate, calcium hydrogen phosphate, D-mannitol, citric acid, sweet orange essence, magnesium stearate, sucralose and polyvidone K30;
the following steps are included in S2:
s2-1: preparing adhesive, weighing polyvidone K30, adding purified water, stirring to dissolve uniformly to obtain 2% polyvidone slurry, adding sucralose and vitamin D3Adding the combined powder and citric acid into the povidone slurry, and uniformly stirring for later use;
s2-2: pouring weighed materials of L-calcium lactate, calcium hydrophosphate, D-mannitol and sweet orange essence into a high-efficiency wet mixing granulator, adding an adhesive to prepare a soft material, and then granulating on a swinging granulator by using a 24-mesh nylon screen;
the following steps are included in S3: drying the prepared wet granules by using an oven at the temperature of 55 +/-5 ℃ until the drying weight loss of the granules meets the requirement, and finishing the granules by using a 24-mesh screen;
the following steps are included in S4: putting the dry granules and the magnesium stearate into a mixer and uniformly mixing;
the following steps are included in S5: tabletting according to the marked weight of 1.2 g/tablet, and checking the appearance and weight of the tablet at regular time;
the following steps are included in S6: performing inner packaging according to the operation rules of the equipment, and clearing the field according to the requirements after the production is finished;
the following steps are included in S7: and (5) packing and boxing the small boxes.
After the research and improvement of the embodiment, the L-calcium lactate has little bitter taste, slightly sour taste, but no heavy weight, and is more suitable for most people. Further, through sample analysis, the acceptability of the taste is tested and divided into three types of preference, common preference and dislike, and the result shows that the proportion of favorite people is more than 90%.
The calcium supplement agent of the product is organic calcium L-calcium lactate, has the levorotatory characteristic, is compatible with the levorotatory physiological characteristic of a human body, and has good solubility. However, L-calcium lactate has bitter taste, the bitter taste is reduced by using a sweetening agent of sucralose, D-mannitol with sweetness and good mouthfeel and citric acid with sour taste, and sweet orange essence is added, so that the L-calcium lactate has light faint scent and is more suitable for the taste of most people. The tablet is not sticky and smooth and does not crack.
It should be noted that different types of flavoring agents are selected in the process of obtaining the components according to the above mixture weight, and the mixture weights of the multiple flavoring agents are repeatedly compared, so that the above component mixture meeting the taste of most people is finally obtained, and the following contents show some other representative types of embodiments, but the taste of the components obtained in the embodiments is not good enough.
Control group 1:
the formula is as follows:
Figure BDA0002256030320000071
Figure BDA0002256030320000081
the production process comprises the following steps:
and (2) preparing the pulp, namely weighing povidone K30(2.48g), adding 121.52g of purified water, uniformly stirring to obtain 2% povidone K30 solution, weighing citric acid (20g) and sucralose (0.6g), dissolving in 100g of 2% povidone K30 pulp, and stirring to dissolve to obtain the pulp ① for later use.
Mixing: weighing vitamin D3Mixing the combined powder (0.31g), L-calcium lactate (pentahydrate) (103.61g), calcium hydrogen phosphate (105.64g), D-mannitol (501.86g) and orange essence (7.5g) by hand for 5min to obtain material ①.
And (3) preparing a soft material, namely dissolving the material ① in ① slurry to prepare the soft material, adding 24g of 2% povidone K30 slurry, forming the soft material, and granulating on a swing granulator by using a 24-mesh nylon sieve.
And (3) drying: and (3) putting the prepared wet granules into a hot air circulation oven, setting the temperature to be 50 +/-5 ℃, starting the equipment, recording the starting time and the temperature, and drying until the drying weight loss of the granules is less than or equal to 5%.
Mixing: the dried granules were added with magnesium stearate (8g) and mixed by hand for 5 min.
Tabletting: tabletting was carried out at the indicated weight of 1.5 g/tablet, and the appearance and weight of the tablets were checked at regular intervals.
And (4) analyzing results: the tablet has good taste and slight sticking. There is still a problem due to the sticking phenomenon during the tabletting process.
Control group 2:
the formula is as follows:
Figure BDA0002256030320000082
Figure BDA0002256030320000091
2. the production process comprises the following steps:
(1) slurry preparation: weighing polyvidone K30(2.4g), adding purified water 117.6g, stirring to dissolve to obtain 2% polyvidone K30 solution, weighing citric acid (10.0g) and sucralose (0.4g), adding 2% polyvidone K30 slurry, stirring to dissolve, and keeping.
(2) Mixing: weighing vitamin D3Mixing the combined powder (0.31g), L-calcium lactate (pentahydrate) (103.61g), calcium hydrogen phosphate (105.64g), D-mannitol (367.64g) and orange essence (5.0g) by hand for 5min to obtain material ①.
(3) And (3) preparing a soft material, namely dissolving the material ① in 120g of 2% povidone K30 slurry to prepare the soft material, forming the soft material, and granulating on a swing granulator by using a 24-mesh nylon sieve.
(4) And (3) drying: and (3) putting the prepared wet granules into a hot air circulation oven, setting the temperature to be 50 +/-5 ℃, starting the equipment, recording the starting time and temperature, and drying until the drying weight loss of the granules is less than or equal to 6.9%.
(5) Mixing: the dried granules were added with magnesium stearate (5.0g) and mixed by hand for 5 min.
(6) Tabletting: tabletting was carried out at the indicated weight of 1.2 g/tablet, and the appearance and weight of the tablets were checked at regular intervals.
And (4) analyzing results: the tablet has good taste and slight sticking. There is still a problem due to the sticking phenomenon during the tabletting process.
Control group 3:
1. the formula is as follows
Figure BDA0002256030320000101
2. The production process comprises the following steps:
slurry preparation: weighing polyvidone K30(10g) and vitamin D3Adding 0.49kg of purified water into the combined powder (1.9g), the citric acid (60.0g) and the sucralose (2.4g), stirring and dissolving to obtain slurry ①, weighing the povidone K30(4.4g), adding 0.216kg of purified water, stirring and dissolving to obtain slurry ② for later use.
Mixing, weighing L-calcium lactate (pentahydrate) (621.63g), calcium hydrogen phosphate (633.84g), D-mannitol (2193.83g) and orange essence (36g), adding into a mixing granulator, and mixing for 5min to obtain material ① for use.
And (3) preparing soft materials, namely adding the material ① into the slurry ① to prepare soft materials, molding the soft materials (the slurry ② is not used), and granulating the soft materials on a swinging granulator by using a 24-mesh nylon sieve.
And (3) drying: and (3) putting the prepared wet granules into a hot air circulation oven, setting the temperature to be 55 +/-5 ℃, starting the equipment, recording the starting time and temperature, and drying until the drying weight loss of the granules is less than or equal to 5.38%.
Mixing: the dried granules were added with magnesium stearate (36g) and mixed by hand for 5 min.
Tabletting: tabletting was carried out at the indicated weight of 1.2 g/tablet, and the appearance and weight of the tablets were checked at regular intervals.
And (4) analyzing results: the purpose of this test is to verify the feasibility of granulation, which is possible. But the tablets were slightly sticky.
Control group 4:
1. the formula is as follows:
Figure BDA0002256030320000111
2. the production process comprises the following steps:
slurry preparation: weighing polyvidone K30(0.0332kg) and dissolving in purified water 1.626kg, stirring to dissolve, weighing sucralose (0.008kg) and vitamin D3Adding the combined powder (0.0063kg) and citric acid (0.2kg), and stirring to obtain slurry ①.
Weighing L-calcium lactate (pentahydrate) (2.072kg), calcium hydrogen phosphate (2.112kg), D-mannitol (7.304kg) and sweet orange essence (0.12kg), dry mixing in a high efficiency wet granulator for 5min, adding ① slurry to make soft mass for 1min, shaking for 24 mesh, and finishing for 24 mesh.
And (3) drying: and (3) putting the prepared wet granules into a hot air circulation oven, setting the temperature to be 55 +/-5 ℃, starting the equipment, recording the starting time and temperature, and drying until the drying weight loss of the granules is less than or equal to 4.29%.
Mixing: drying, grading with 24 mesh sieve, adding magnesium stearate (0.144kg), and mixing for 5 min.
Tabletting: tabletting was carried out at the indicated weight of 1.2 g/tablet, and the appearance and weight of the tablets were checked at regular intervals.
And (4) analyzing results: the purpose of this test is to test the tablet, can press the tablet, the tablet is smooth, does not split.
The L-calcium lactate pentahydrate used in the above examples and control was prepared by the following steps:
performing Sa strain culture, namely placing rhizopus oryzae in a corn starch pilot tube for slant culture for 7-10 d, inoculating the rhizopus oryzae into a triangular flask, performing seed culture on a shaking table, inoculating the rhizopus oryzae into a seed tank for fermentation culture after 20-24 h, wherein the fermentation culture time is 16-20 h; wherein the inoculation amount of the rhizopus oryzae is 5-10% v/v, sterile compressed air needs to be introduced into a seeding tank, the ventilation amount is 0.5v/v ∙ min, the temperature of the seeding tank is 34 ℃, and a nitrogen source added into the seeding tank is ammonium sulfate;
preparing an Sb fermentation culture medium, namely preparing starch slurry from corn starch, excessive neutralizer calcium carbonate and alpha-amylase, adding the starch slurry into a fermentation tank, adding nutrient salt and ammonium sulfate, uniformly stirring, introducing 0.1MPa steam into the fermentation tank for sterilization for 20min, then introducing cooling water into a coil pipe, and cooling the culture medium to 34 ℃; wherein the adding amount of the corn starch is 13 percent of the total mass of the culture medium, the concentration of the alpha-amylase in the culture medium is 5-10 mug/g, and the filling amount of the culture medium in a fermentation tank is 70 percent;
sc fermentation, namely inoculating the strain cultured in the step Sa into a fermentation culture medium, introducing sterile compressed air, and culturing for 32-34 h; wherein the inoculation amount of the strain accounts for 5-10% of the volume of the culture medium, the ventilation amount of the sterile compressed air is 0.5v/v ∙ min, the tank pressure is 0.1MPa and the temperature is 34 ℃ in the fermentation process; a cyclone separator is arranged on an exhaust pipe of the fermentation tank, and feed liquid obtained by separating foam generated in the fermentation process is introduced into the fermentation tank;
sd fermentation liquor treatment, adding active carbon into the fermentation liquor obtained in the step Sc, continuously stirring for decoloring and deodorizing, filtering again, and transferring the filtrate into a crystallizer;
se crystallization, namely adjusting the pH value of the filtrate in the Sd crystallizer to 6.5-7.5, adding ethanol at a constant temperature of 35 ℃, cooling to 5-10 ℃, filtering and separating, washing a filter cake with ethanol, and drying the filter cake to obtain L-calcium lactate pentahydrate; wherein the adding amount of the ethanol is 3-5 times of the total volume of the fermentation liquor, and the adding mode of the ethanol is as follows: 1/5 of the total amount of ethanol is added at a constant speed within 0-30 min, 2/5 of the total amount of ethanol is added at a constant speed within 30-60 min, and 2/5 of the total amount of ethanol is added at a constant speed within 60-180 min; the cooling mode is that the mixture is stood and naturally cooled to 20 ℃, and then is rapidly cooled to 5-10 ℃ within 5 min; the drying temperature is 50-55 ℃, the pressure during drying is 0.08-0.09 MPa, and the drying time is 2-3 h.
The invention relates to a preparation process of L-calcium lactate pentahydrate, which is characterized in that the crystallization process adopts a dissolution method to be matched with cooling crystallization, the further optimization is that the adding mode and the cooling mode of a dissolution agent ethanol are limited, the obtained L-calcium lactate crystal main granularity is ensured to be larger than 19 mu m within the limited condition range of the invention, the yield of the crystallization reaches more than 85 percent, and the L-type content in the obtained L-calcium lactate crystal reaches more than 99.95 percent.
Control groups 5 and 6
The comparison tests of the first embodiment are shown in the comparison groups 5 and 6, and the difference is that the temperature of the Se crystallization process in the preparation method of the L-calcium lactate pentahydrate in the comparison group 5 is firstly reduced from 35 ℃ to 20 ℃ within 5min, and then is naturally reduced to 5-10 ℃; the ethanol addition in the Se crystallization step of the process for the preparation of L-calcium lactate pentahydrate in control 6 was performed in such a way that all ethanol was added at uniform rate over 180min, and the remaining steps and parameters of controls 5 and 6 were the same as in the first example. As a result, the L-type content of the L-calcium lactate crystals prepared in the control group 5 was 87%, the crystal primary particle size was 15 μm, the crystal yield was 82%, the calcium vitamin D chewable tablets prepared were subjected to taste tests and classified into favorite, general and disliked three types, and the results showed that the proportion of favorite groups was 75%; the content of the L-type in the L-calcium lactate crystals prepared in the control group 6 is 85%, the main particle size of the crystals is 16 mu m, the crystallization yield is 83%, and the prepared calcium vitamin D chewable tablets are subjected to taste tests and divided into favorite, common and disliked three types, and the result shows that the proportion of favorite groups is 79%; and the calcium vitamin D chewable tablet prepared by the control groups 5 and 6 has different sticking during the tabletting process.
It is to be understood that the described embodiments are merely a few embodiments of the invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Claims (7)

1. The calcium vitamin D chewable tablet is characterized by comprising the following components in parts by weight:
211.28 portions of calcium hydrophosphate plus or minus 1 percent;
207.22 portions of L-calcium lactate pentahydrate +/-1 percent;
vitamin D30.63 part of composite powder +/-1%;
730.35 portions of D-mannitol +/-1 percent;
20.00 parts of citric acid +/-1%;
14.40 parts of magnesium stearate +/-1%;
3.32 parts of povidone K30 +/-1%;
0.80 part of sucralose +/-1 percent;
the orange essence accounts for 12.00 parts plus or minus 1 percent.
2. The calcium vitamin D chewable tablet of claim 1,
211.28 parts of calcium hydrophosphate;
207.22 parts of L-calcium lactate pentahydrate;
vitamin D30.63 part of composite powder;
730.35 parts of D-mannitol;
20.00 parts of citric acid;
14.40 parts of magnesium stearate;
3.32 parts of povidone K30;
0.80 part of sucralose;
the orange essence accounts for 12.00 parts.
3. The calcium vitamin D chewable tablet of any one of claims 1 or 2, wherein each of the chewable tablets is a calcium vitamin D chewable tabletKevitamine D3The composition powder contains sucrose 175mg, sodium ascorbate 40mg, and vitamin D32.5mg, octyl, tricaprin 30mg, silicon dioxide 12mg, dl-alpha-tocopherol 10mg and sodium starch octenyl succinate 730.5 mg.
4. A process for the preparation of chewable calcium vitamin D tablets according to claims 1 to 3, characterized in that it comprises the following steps:
s1: weighing and proportioning;
s2: granulating;
s3: drying;
s4: mixing;
s5: tabletting;
s6: packaging in an inner package;
s7: and (6) outer packaging.
5. The process for preparing a calcium vitamin D chewable tablet according to claim 4, characterized in that it comprises the following steps:
in S1, vitamin D is weighed3The preparation method comprises the following steps of (1) filling weighed materials into a container or a material bag, sealing, and attaching a material label to the outer layer of the container or the material bag for later use, wherein the materials comprise combined powder, L-calcium lactate pentahydrate, calcium hydrogen phosphate, D-mannitol, citric acid, sweet orange essence, magnesium stearate, sucralose and polyvidone K30;
the following steps are included in S2:
s2-1: preparing adhesive, weighing polyvidone K30, adding purified water, stirring to dissolve uniformly to obtain 2% polyvidone slurry, adding sucralose and vitamin D3Adding the combined powder and citric acid into the povidone slurry, and uniformly stirring for later use;
s2-2: pouring weighed materials of L-calcium lactate pentahydrate, calcium hydrophosphate, D-mannitol and sweet orange essence into a high-efficiency wet mixing granulator, adding a binder to prepare a soft material, and then granulating on a swinging granulator by using a 24-mesh nylon screen;
the following steps are included in S3: drying the prepared wet granules by using an oven at the temperature of 55 +/-5 ℃ until the drying weight loss of the granules meets the requirement, and finishing the granules by using a 24-mesh screen;
the following steps are included in S4: putting the dry granules and the magnesium stearate into a mixer and uniformly mixing;
the following steps are included in S5: tabletting according to the marked weight of 1.2 g/tablet, and checking the appearance and weight of the tablet at regular time;
the following steps are included in S6: performing inner packaging according to the operation rules of the equipment, and clearing the field according to the requirements after the production is finished;
the following steps are included in S7: and (5) packing and boxing the small boxes.
6. The method of claim 5, wherein the L-calcium lactate pentahydrate is prepared in step S1 as follows:
performing Sa strain culture, namely placing rhizopus oryzae in a corn starch pilot tube for slant culture for 7-10 d, inoculating the rhizopus oryzae into a triangular flask, performing seed culture on a shaking table, inoculating the rhizopus oryzae into a seed tank for fermentation culture after 20-24 h, wherein the fermentation culture time is 16-20 h;
preparing an Sb fermentation culture medium, namely preparing starch slurry from corn starch, excessive neutralizer calcium carbonate and alpha-amylase, adding the starch slurry into a fermentation tank, adding nutrient salt and ammonium sulfate, uniformly stirring, introducing 0.1MPa steam into the fermentation tank for sterilization for 20min, and then cooling the culture medium to 34 ℃;
sc fermentation, namely inoculating the strain cultured in the step Sa into a fermentation medium prepared from Sb, introducing sterile compressed air, and culturing for 32-34 h;
sd fermentation liquor treatment, adding active carbon into the fermentation liquor obtained in the step Sc, continuously stirring for decoloring and deodorizing, filtering again, and transferring the filtrate into a crystallizer;
se crystallization, namely adjusting the pH value of the filtrate in the Sd crystallizer to 6.5-7.5, adding ethanol at a constant temperature of 35 ℃, cooling to 5-10 ℃, filtering and separating, and collecting a filter cake;
sf washing the filter cake with ethanol, and drying the filter cake to obtain the L-calcium lactate pentahydrate.
7. The method of preparing calcium vitamin D chewable tablets according to claim 6,
in the step Sa, the inoculation amount of the rhizopus oryzae is 5-10% v/v, sterile compressed air needs to be introduced into a seeding tank, the ventilation amount is 0.5v/v ∙ min, the temperature of the seeding tank is 34 ℃, and a nitrogen source added into the seeding tank is ammonium sulfate;
in the step Sb, the adding amount of the corn starch is 13% of the total mass of the culture medium, the concentration of the alpha-amylase in the culture medium is 5-10 mu g/g, and the filling amount of the culture medium in a fermentation tank is 70%;
the inoculation amount of the strains in the step Sc accounts for 5-10% of the volume of the culture medium, the ventilation amount of sterile compressed air is 0.5v/v ∙ min, the tank pressure is 0.1MPa and the temperature is 34 ℃ in the fermentation process; a cyclone separator is arranged on an exhaust pipe of the fermentation tank, and feed liquid obtained by separating foam generated in the fermentation process is introduced into the fermentation tank;
the adding amount of the ethanol in the step Se is 3-5 times of the total volume of the fermentation liquor, and the adding mode of the ethanol is as follows: 1/5 of the total amount of ethanol is added at a constant speed within 0-30 min, 2/5 of the total amount of ethanol is added at a constant speed within 30-60 min, and 2/5 of the total amount of ethanol is added at a constant speed within 60-180 min; the cooling mode is that the mixture is stood and naturally cooled to 20 ℃, and then is rapidly cooled to 5-10 ℃ within 5 min;
the drying temperature in the step Sf is 50-55 ℃, the pressure during drying is 0.08-0.09 MPa, and the drying time is 2-3 h.
CN201911063035.9A 2019-10-31 2019-10-31 Calcium vitamin D chewable tablet and preparation method thereof Pending CN110693901A (en)

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