CN110227079B - Five-vitamin lysine granules and preparation method thereof - Google Patents
Five-vitamin lysine granules and preparation method thereof Download PDFInfo
- Publication number
- CN110227079B CN110227079B CN201910482389.0A CN201910482389A CN110227079B CN 110227079 B CN110227079 B CN 110227079B CN 201910482389 A CN201910482389 A CN 201910482389A CN 110227079 B CN110227079 B CN 110227079B
- Authority
- CN
- China
- Prior art keywords
- vitamin
- lysine
- particles
- buffer solution
- buffer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- 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, pantothenic 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- 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, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1658—Proteins, e.g. albumin, gelatin
-
- 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
Abstract
The invention relates to five-dimensional lysine particles, which comprise separately packaged particles A and particles B, wherein the particles A comprise lysine hydrochloride, calcium pantothenate and vitamin B 2 Vitamin B 6 A binder, sucrose and a first buffer; the pH of the first buffer is 6.0-7.0 in a solution state; the B granule comprises lysine hydrochloride and vitamin B 1 Vitamin B 2 Vitamin B 6 Nicotinamide, a binder, sucrose and a second buffer; the pH of the second buffer is 3.0-5.5 in a solution state; lysine hydrochloride and vitamin B in the granules A and B 2 And vitamin B 6 The mass ratio of (A) to (B) is 1: 1. Calcium pantothenate and vitamin B in pentavitamin lysine granules of the present invention 1 The stability is improved.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to five-vitamin lysine granules and a preparation method thereof.
Background
The five-vitamin lysine granules are vitamin over-the-counter prescription preparation, and each gram of the five-vitamin lysine granules contains 50 mg of lysine hydrochloride and 1.2 mg of vitamin B 1 0.15 mg of vitamin B 2 0.075 mg vitamin B 6 2.4 mg of nicotinamide, 0.15 mg of calcium pantothenate and the balance of cane sugar serving as an auxiliary material are used for promoting the normal development of children and supplementing the nutrition of the old and the weak.
The five-dimensional lysine granules can reasonably supplement the requirements of human bodies according to the growth and development characteristics of children. Lysine can promote growth and development and repair damaged nerve tissues; vitamin B 1 And B 6 Participate in the formation of coenzyme in vivo and promote metabolism in vivo; calcium pantothenate is involved in the formation of human bone, the reconstruction of bone tissue, muscle contraction, neurotransmission, blood coagulation mechanism, and the maintenance of capillary permeability. The five-dimensional lysine granules can supplement lysine lost by children patients, not only can enhance physique and improve disease resistance, but also can promote the secretion of pepsin of the children patients, thereby forming a virtuous cycle effect in the treatment process.
The main component of the pentavitamin lysine granule is water-soluble vitamin with low stability, especially vitamin B 1 And calcium pantothenate are susceptible to environmental factors such as light, high temperature and water, resulting in high requirements for transportation and storage conditions and greatly limited applications.
The national drug standard has already loaded five-dimensional lysine particles, but the stability problem is very critical due to low content of main components, and if slight content change exists, the quality of the five-dimensional lysine particles is obviously influenced. Chinese patent publication No. CN107233305A discloses a pentavitamin lysine oral liquid, CN201510217486.9 discloses a lysine pentavitamin pharmaceutical composition containing chiral isomeric compound and its use. At present, vitamin B in five-vitamin lysine granules is not seen 1 And the research report related to the stability of calcium pantothenate.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide a pentavitamin lysine granule and a preparation method thereof, which can improve the stability of easily degradable components of vitamin B1 and calcium pantothenate in a prescription and prolong the storage life in different environments, thereby ensuring the quality and effectiveness of the preparation.
The first purpose of the invention is to provide five-dimensional lysine granules, which comprise separately packaged A granules and B granules, wherein the A granules comprise lysine hydrochloride, calcium pantothenate and vitamin B 2 Vitamin B 6 Nicotinamide, binder, sucrose and a first buffer; the pH of the first buffer is 6.0-7.0 in a solution state;
the B granule comprises lysine hydrochloride and vitamin B 1 Vitamin B 2 Vitamin B 6 A binder, sucrose and a second buffer; the pH of the second buffer is 3.0-5.5 in a solution state;
lysine hydrochloride and vitamin B in the granules A and B 2 And vitamin B 6 The mass ratio of (A) to (B) is 1: 1.
Preferably, the first buffer has a pH of 6.0 to 6.8, more preferably 6.3 to 6.5, in the solution state.
Preferably, the second buffer has a pH of 3.5 to 4.0 in a solution state.
Furthermore, each gram of the five-vitamin lysine granules comprises 50 mg of lysine hydrochloride and 1.2 mg of vitamin B 1 0.15 mg of vitamin B 2 0.075 mg vitamin B 6 2.4 mg nicotinamide, 0.15 mg calcium pantothenate, 920-.
Further, the adhesive is selected from one or more of starch slurry, dextrin, gelatin, sodium carboxymethyl cellulose, PVP and ethanol.
Further, the binder is preferably ethanol, PVP or dextrin.
Further, the volume of the buffer solution used for every 50g of the A particles or the B particles is 1.5-2.5 mL, the buffer solution comprises a first buffer or a second buffer, and the concentration of the buffer solution is 0.01mol -1 ～0.2mol.L -1 And the buffer solution contains 60% (w/v) to 90% (w/v) ethanol, 1% (w/v) to 10% (w/v) PVP or 1% (w/v) to 10% (w/v) dextrin.
Further, the first buffer and the second buffer are selected from one or two of citric acid-sodium hydroxide, citric acid-sodium citrate, potassium hydrogen phthalate-sodium hydroxide, acetic acid-sodium acetate, acetic acid-potassium acetate, acetic acid-ammonium acetate, phosphoric acid-phosphoric acid citric acid, sodium dihydrogen phosphate-disodium hydrogen phosphate, potassium dihydrogen phosphate-dipotassium hydrogen phosphate, sodium dihydrogen phosphate-sodium hydroxide and potassium dihydrogen phosphate-sodium hydroxide.
Preferably, the first buffer and the second buffer are citric acid-sodium citrate.
Furthermore, the five-vitamin lysine granules also comprise a flavoring agent.
The second purpose of the invention is to provide a preparation method of the five-dimensional lysine particles, which comprises the following steps:
(1) dissolving an adhesive, a first buffer solution and a second buffer solution in water respectively to obtain a first buffer solution and a second buffer solution, wherein the pH value of the first buffer solution is 6.0-7.0, and the pH value of the second buffer solution is 3.0-5.5;
(2) respectively and uniformly mixing 1/2 prescription amount of sucrose and 1/2 prescription amount of lysine hydrochloride to obtain powder;
mixing calcium pantothenate and 1/2 prescribed amount of vitamin B 2 1/2 prescription amounts of vitamin B 6 Dissolving in a first buffer solution, uniformly mixing the obtained solution and powder, and performing wet granulation and drying to obtain granules A;
mixing vitamin B 1 Nicotinamide 1/2 prescription amount of vitamin B 2 And 1/2 prescription amounts of vitamin B 6 Dissolving in a second buffer solution, uniformly mixing the obtained solution and powder, and performing wet granulation and drying to obtain B granules;
and respectively packaging the particles A and the particles B to obtain the five-dimensional lysine particles.
Further, the binder is preferably ethanol, PVP or dextrin. The first buffer solution or the second buffer solution contains 60% (w/v) to 90% (w/v) ethanol, 1% (w/v) to 10% (w/v) PVP or 1% (w/v) to 10% (w/v) dextrin.
Preferably, the pH of the first buffer is 6.0-6.8, more preferably 6.3-6.5.
Preferably, the pH of the second buffer is between 3.0 and 5.5, more preferably between 3.5 and 4.0.
Further, in the step (1), the concentration of the first buffer or the second buffer is 0.01mol -1 ～0.2mol.L -1 。
Further, in the step (2), the sucrose and the lysine hydrochloride are sieved by a sieve of 80-100 meshes before being mixed.
Further, in the step (2), during wet granulation, the obtained granules are sieved by a sieve with 18-28 meshes.
Further, in step (2), each time 50g A granules were prepared, calcium pantothenate and 1/2 prescribed amounts of vitamin B 2 1/2 prescription amounts of vitamin B 6 Dissolving in 2mL of first buffer solution, spraying the obtained solution on the surface of the powder, mixing uniformly, spraying 1.5mL of first buffer solution, making into soft material, sieving, extruding, granulating, and drying to obtain granule A.
Further, in the step (2), every time the 50g B granules are prepared, vitamin B is added 1 Nicotinamide 1/2 prescribed amount of vitamin B 2 And 1/2 prescription amounts of vitamin B 6 Dissolving in 1-2mL of second buffer solution, spraying the obtained solution on the surface of the powder, mixing uniformly, spraying 1-1.5mL of second buffer solution, making into soft material, sieving, extruding, granulating, and drying to obtain granule A.
Further, in the step (2), the drying temperature was 40 ℃.
A, B granules are respectively prepared according to the physicochemical properties and the color of the medicine, the pH value of the adhesive is adjusted by buffer solution to meet the requirement of vitamin B 1 And calcium pantothenate; through separate packaging, the change of the pH value of the medicine caused by moisture absorption or solvent volatilization is further prevented, and the constancy of the pH value of the medicine environment is ensured, thereby realizing the vitamin B 1 And stability of calcium pantothenate.
By the scheme, the invention at least has the following advantages:
(1) the five-vitamin lysine particles prepared by the invention respectively control the pH value of the environment of the drug particles through a buffer solution system, and fully ensure vitamin B 1 And stability of calcium pantothenate.
(2) The five-vitamin lysine particles prepared by the invention adopt the adhesive auxiliary materials with the least amount as possible, do not influence the determination of the medicine content, have no change in taste, are suitable for the old and children, and can obviously improve the medication compliance of patients
(3) The preparation method of the five-vitamin lysine granules disclosed by the invention adopts a wet granulation method, has a simple process and controllable preparation conditions, and is beneficial to industrial production.
The foregoing is a summary of the present invention, and in order to provide a clear understanding of the technical means of the present invention and to be implemented in accordance with the present specification, the following is a preferred embodiment of the present invention and is described in detail below.
Detailed Description
The following examples are given to further illustrate embodiments of the present invention. The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.
In the following practice of the invention, vitamin B is present in pentavitamin lysine granules 1 And calcium pantothenate as follows:
the obtained pentavitamin lysine particles are respectively placed in a room temperature (25 ℃), a constant temperature and humidity box (40 ℃, 75% RH) and a drying box (60 ℃), and are stored in a dark place, and the samples are taken in 0, 5, 10, 20 and 30 days. Precisely weighing 1g of sample, adding distilled water, dissolving in 20mL volumetric flask, filtering with 0.45 μm filter membrane, collecting supernatant, performing HPLC analysis, and calculating vitamin B 1 And the content of calcium pantothenate (n ═ 3).
Calcium pantothenate and vitamin B in pentavitamin lysine granules 1 The HPLC analysis conditions of (1) are as follows:
(1) determination of the content of calcium pantothenate: chromatography column, C 18 Reverse phase chromatography column (250 mm. times.4.6 mm,5 μm); mobile phase, methanol: water (containing 0.1% phosphoric acid) 20:80 (V/V); detection wavelength, 210 nm; column temperature, 30 ℃; flow rate, 1mL.min -1 (ii) a Sample size, 20 μ L.
(2) Vitamin B 1 The content determination of (A): chromatography column, C 18 Reverse phase chromatography column (150 mm. times.4.6 mm,5 μm); mobile phase, 0.008mol.L -1 Hexane sulfonic acid sodium salt-methanol-glacial acetic acid-triethylamine (7)75:220:7.5: 0.2); detection wavelength, 280 nm; column temperature, 30 ℃; flow rate, 1mL.min -1 (ii) a Sample size, 20 μ L.
EXAMPLE preparation of five-dimensional lysine particles
In the invention, each gram of the five-vitamin lysine granules comprises 50 mg of lysine hydrochloride and 1.2 mg of vitamin B 1 0.15 mg of vitamin B 2 0.075 mg vitamin B 6 2.4 mg nicotinamide, 0.15 mg calcium pantothenate, 920 + 950 mg sucrose. The preparation method comprises the following steps:
(1) preparing an adhesive: anhydrous citric acid and sodium citrate were weighed to pH6.6 and pH4.0(0.1mol. L), respectively -1 ) And (4) a buffer solution. 100mL of buffer solution is measured respectively, 7g of dextrin is added, the mixture is heated in a water bath at 100 ℃ for 5min to be dissolved, and 7% dextrin pulp buffer solutions with the pH value of 6.6 and the pH value of 4.0 are prepared respectively.
(2) Preparation of particles A: 1/2 prescription amount of sucrose and 1/2 prescription amount of lysine hydrochloride are weighed (sieved 80) # ) Then, the mixture was transferred to a beaker (1L) and mixed to obtain a powder. Calcium pantothenate, 1/2 prescription dose of vitamin B 2 And 1/2 prescription amounts of vitamin B 6 Dissolving in 2mL of 7% dextrin slurry buffer solution with pH of 6.6, spraying 1.0mL of the obtained solution into about 50g of precisely weighed powder, mixing uniformly, spraying 1.0mL of 7% dextrin slurry buffer solution with pH of 6.6 into the mixture, mixing uniformly, preparing a soft material, extruding and granulating through a 24-mesh screen, and drying in an oven at 40 ℃ for 30min to obtain the high-performance starch-free starch-based composite material.
(3) B, preparing particles: 1/2 prescription amount of sucrose is weighed (sieved 80) # ) And 1/2 prescription amount of lysine hydrochloride (sieving 80) # ) Then, the mixture was transferred to a beaker (1L) and mixed to obtain a powder. Mixing vitamin B 1 1/2 prescription amounts of vitamin B 2 1/2 prescription amounts of vitamin B 6 Dissolving nicotinamide and 7% dextrin slurry buffer solution with pH of 4.0 at 1.0 mLl, spraying the obtained solution into about 50g of precisely weighed powder, mixing uniformly, spraying 7% dextrin slurry buffer solution with pH of 4.0 at about 1.0 mLl into the mixture, mixing uniformly, preparing a soft material, extruding and granulating through a 24-mesh screen, and drying in an oven at 40 ℃ for 30min to obtain the nicotinamide powder.
Packaging the granules A and B with self-sealing bags, wherein each bag contains 1g of vitaminB 1 And calcium pantothenate were separately investigated for stability. The results are shown in Table 1.
TABLE 1 vitamin B 1 And calcium pantothenate stability test results (%, average. + -. SD, n ═ 3)
The stability test results show that, under the scheme of the invention, calcium pantothenate and vitamin B 1 All had higher stability, and the content at 30d was still more than 90% of the original content.
EXAMPLE preparation of Diwuweilysine particles
This example investigates the effect of buffer concentration on the stability of calcium pantothenate in pentavitamin lysine particles.
(1) Preparing an adhesive: anhydrous citric acid and sodium citrate were weighed and set to pH6.6 and pH5.2, respectively (the concentration of the buffer solution at each pH condition was 0.1mol. L, respectively -1 And 0.01mol.L -1 ) And (4) buffering the solution. 100mL of the buffer solution was measured, 7g of dextrin was added thereto, and the mixture was dissolved by heating in a water bath at 100 ℃ for 5min to prepare 7% dextrin slurry buffer solutions having pH6.6 and pH5.2, respectively.
(2) Preparation of particles A: 1/2 prescription amount of sucrose and 1/2 prescription amount of lysine hydrochloride are weighed (sieved 80) # ) Then, the mixture was transferred to a beaker (1L). Calcium pantothenate, 1/2 prescription dose of vitamin B 2 And 1/2 prescription amounts of vitamin B 6 Dissolving in 7% dextrin pulp buffer solution with pH of 6.6 at 1ml, spraying the obtained solution into about 50g of precisely weighed powder, mixing, spraying and adding 7% dextrin pulp buffer solution with pH of 6.6 at 1.0ml into the mixture, mixing, making soft material, extruding and granulating through a 24-mesh screen, and drying in an oven at 40 deg.C for 30min to obtain the final product.
(3) B, preparing particles: 1/2 prescription amount of sucrose is weighed (sieved 80) # ) And 1/2 prescription amount of lysine hydrochloride (sieving at 80) # ) Transferring to a beaker (1L), and mixing to obtain powder. Mixing vitamin B 1 1/2 prescription amount of vitamin B 2 1/2 prescription amount of vitamin B 6 And nicotinamide in 7% dextrin pulp buffer solution at pH5.2 at 1.0mlSpraying the obtained solution on about 50g of precisely weighed powder, uniformly mixing, then spraying 7% dextrin pulp buffer solution with pH of about 1.0ml and 5.2 into the mixture, uniformly mixing, preparing a soft material, extruding and granulating through a 24-mesh screen, and drying in an oven at 40 ℃ for 30min to obtain the finished product.
Packaging 2g of the granules A and B in a self-sealing bag (1: 1) per bag, and packaging the vitamin B in the granules 1 And calcium pantothenate were separately investigated for stability. The results are shown in tables 2 to 3.
Table 2. buffer concentration effect on calcium pantothenate stability in pentavitamin lysine particles (%, Mean ± SD, n ═ 3)
TABLE 3 buffer concentration vs. vitamin B in pentavitamin lysine granulate 1 Stability impact (%, Mean ± SD, n ═ 3)
As can be seen from tables 2-3, vitamin B was produced by preparing granules A and B and adjusting the appropriate pH values, respectively 1 The content of calcium pantothenate is more than 90%, and the process remarkably improves the stability of the two medicines.
Comparative example preparation of five-dimensional lysine granules
(1) Preparing an adhesive: anhydrous citric acid and sodium citrate were weighed and prepared to pH5.8 and pH5.5(0.1mol. L), respectively -1 ) The buffer solution is measured to 100mL respectively, 7g of dextrin is added, the mixture is heated in a water bath at 100 ℃ for 5min to be dissolved, and 7% dextrin pulp buffer solutions with pH of 5.8 and pH of 5.5 are prepared respectively.
(2) Preparation of particles A: 1/2 prescription amount of sucrose and 1/2 prescription amount of lysine hydrochloride are weighed (sieved 80) # ) Then, the mixture was transferred to a beaker (1L) and mixed to obtain a powder. Calcium pantothenate, 1/2 prescribed amount of vitamin B 2 And 1/2 prescription amounts of vitamin B 6 Dissolving in 1mL of 7% dextrin slurry buffer solution with pH of 5.5, and spraying the obtained solution onto a precision sprayWeighing about 50g of powder, mixing, spraying 7% dextrin pulp buffer solution with pH of 5.5 and 1.0ml into the mixture, mixing, making into soft material, sieving with 24 mesh sieve, extruding, granulating, and oven drying at 40 deg.C for 30 min.
(3) B, preparing particles: 1/2 prescription amount of sucrose is weighed (sieved 80) # ) And 1/2 prescription amount of lysine hydrochloride (sieving 80) # ) Transferring to a beaker (1L) and mixing to obtain powder. Mixing vitamin B 1 1/2 prescription amount of vitamin B 2 1/2 prescription amounts of vitamin B 6 Dissolving nicotinamide and nicotinamide in 1.0ml of 7% dextrin slurry buffer solution with pH of 5.8, spraying into about 50g of precisely weighed powder, mixing, spraying 7% dextrin slurry buffer solution with pH of 5.8 and about 1.0ml of the mixture, mixing, making soft material, sieving with 24-mesh sieve, extruding, granulating, and oven drying at 40 deg.C for 30min to obtain the final product.
Adopting self-sealing bags, packaging granule A and granule B separately, each bag containing 1g of vitamin B 1 And calcium pantothenate were separately investigated for stability. The results are shown in Table 4.
TABLE 4 vitamin B 1 And calcium pantothenate stability test results (%, average. + -. SD, n ═ 3)
The results of the stability tests show that calcium pantothenate and vitamin B at pH5.8 and 5.5 of the binder solution 1 Showing a more rapid downward trend.
Comparative example preparation of Diwuweilysine granules
(1) Preparing an adhesive: anhydrous citric acid and sodium citrate were weighed to make pH4.0(0.1 mol.L) -1 ) And (4) buffering the solution. 100mL of buffer solution is measured, 7g of dextrin is added, and the mixture is heated in a water bath at 100 ℃ for 5min to be dissolved to prepare 7% dextrin pulp buffer solution with the pH value of 4.0. In addition, a 7% dextrin aqueous solution was prepared.
(2) Preparation of particles A: 1/2 prescription amount of sucrose and 1/2 prescription amount of lysine hydrochloride are weighed (sieved 80) # ) Transferring to a beaker (1L), and mixing to obtain powder. Calcium pantothenate, 1/2 prescribed amount of vitamin B 2 And 1/2 prescription amounts of vitamin B 6 Dissolving in 1mL of 7% dextrin water solution, spraying the obtained solution into about 50g of precisely weighed powder, mixing, spraying 1.0mL of 7% dextrin water solution into the mixture, mixing, making soft material, extruding and granulating through a 24-mesh screen, and drying in an oven at 40 ℃ for 30min to obtain the final product.
(3) B, preparing particles: 1/2 prescription amount of sucrose (sieving by 80) is weighed out # ) And 1/2 prescription amount of lysine hydrochloride (sieving at 80) # ) And transferring to a beaker (1L) and mixing uniformly to obtain powder. Mixing vitamin B 1 1/2 prescription amounts of vitamin B 2 1/2 prescription amounts of vitamin B 6 Dissolving nicotinamide and 7% dextrin slurry buffer solution with pH of 4.0 at 1.0ml, spraying into about 50g of precisely weighed powder, mixing, spraying 7% dextrin slurry buffer solution with pH of 4.0 at about 1.0ml into the mixture, mixing, making into soft material, sieving with 24 mesh sieve, extruding, granulating, and oven drying at 40 deg.C for 30min to obtain the final product.
Packaging granule A and granule B separately with self-sealing bag, each bag containing 1g of vitamin B 1 And calcium pantothenate were separately investigated for stability. The results are shown in Table 5.
TABLE 5 vitamin B 1 And calcium pantothenate stability test results (%, average. + -. SD, n ═ 3)
The investigation result shows that the content of calcium pantothenate in the particles A which are not subjected to pH adjustment by buffer solution and are used as the adhesive is remarkably reduced; in buffer-adjusted B particles, vitamin B 1 Is more stable.
Comparative example preparation of Tri-five-dimensional lysine granules
Weighing sucrose (sieving 80) # ) And lysine hydrochloride (sieving 80) # ) Then, the mixture was transferred to a beaker (1L) and mixed. Mixing vitamin B 1 Vitamin B 2 Vitamin B 6 Dissolving calcium pantothenate and nicotinamide in 1.0mL of 7% dextrin water solution, spraying into the above powder, mixing, and spraying 1.0mL of 7% paste into the mixtureMixing the refined water solution, making soft material, sieving with 24 mesh sieve, squeezing, granulating, oven drying at 40 deg.C for 30min, packaging with self-sealing bag, and testing stability. The results are shown in Table 6.
TABLE 6 vitamin B 1 And calcium pantothenate stability test results (%, average. + -. SD, n ═ 3)
As can be seen from Table 6, the pentavitamin lysine granules prepared by the conventional method had calcium pantothenate and vitamin B in the drug under the accelerated test conditions 1 The content is in a remarkable descending trend.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, it should be noted that, for those skilled in the art, many modifications and variations can be made without departing from the technical principle of the present invention, and these modifications and variations should also be regarded as the protection scope of the present invention.
Claims (9)
1. A five-dimensional lysine granule characterized by: comprising separately packaged a particles and B particles, the a particles comprising lysine hydrochloride, calcium pantothenate, vitamin B2, vitamin B6, a binder, sucrose, and a first buffer; the pH of the first buffer is 6.0-7.0 in a solution state;
the B particles comprise lysine hydrochloride, vitamin B1, vitamin B2, vitamin B6, nicotinamide, a binder, sucrose and a second buffering agent; the pH of the second buffer is 3.0-5.5 in a solution state;
the first and second buffers are independently selected from the group consisting of citric acid-sodium hydroxide and citric acid-sodium citrate.
2. Five-dimensional lysine particles according to claim 1, characterized in that: each gram of the pentavitamin lysine particles comprises 50 mg of lysine hydrochloride, 1.2 mg of vitamin B1, 0.15 mg of vitamin B2, 0.075 mg of vitamin B6, 2.4 mg of nicotinamide, 0.15 mg of calcium pantothenate and 920 and 950 mg of sucrose.
3. Five-dimensional lysine particles according to claim 1, characterized in that: the adhesive is ethanol or dextrin.
4. Five-dimensional lysine particles according to claim 1, characterized in that: also comprises a flavoring agent.
5. A method of producing five-dimensional lysine particles according to any one of claims 1 to 4, comprising the steps of:
(1) dissolving an adhesive, a first buffer solution and a second buffer solution in water respectively to obtain a first buffer solution and a second buffer solution, wherein the pH value of the first buffer solution is 6.0-7.0, and the pH value of the second buffer solution is 3.0-5.5;
(2) respectively and uniformly mixing 1/2 prescription amount of sucrose and 1/2 prescription amount of lysine hydrochloride to obtain powder;
dissolving calcium pantothenate and 1/2 prescription vitamin B2 and 1/2 prescription vitamin B6 in a first buffer solution, uniformly mixing the obtained solution and the powder, and carrying out wet granulation and drying to obtain A granules;
dissolving vitamin B1, nicotinamide, vitamin B2 in the amount of 1/2 and vitamin B6 in the amount of 1/2 in a second buffer solution, uniformly mixing the obtained solution and the powder, and performing wet granulation and drying to obtain B granules;
and respectively packaging the particles A and the particles B to obtain the five-dimensional lysine particles.
6. The production method according to claim 5, characterized in that: in the step (1), the wetting agent and the adhesive are ethanol and dextrin ethanol solutions with certain concentrations respectively, and the first buffer solution or the second buffer solution contains 60% (w/v) -90% (w/v) ethanol or 1% (w/v) -10% (w/v) dextrin.
7. The method of claim 5, wherein: in step (1), the concentration of the first buffer or the second bufferThe degree is 0.01mol.L -1 ～0.2mol.L -1 。
8. The method of claim 5, wherein: in the step (2), the sucrose and the lysine hydrochloride are sieved by a sieve with 80-100 meshes before being mixed.
9. The production method according to claim 5, characterized in that: in the step (2), during wet granulation, the obtained granules are sieved by a sieve with 18 meshes to 28 meshes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910482389.0A CN110227079B (en) | 2019-06-04 | 2019-06-04 | Five-vitamin lysine granules and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910482389.0A CN110227079B (en) | 2019-06-04 | 2019-06-04 | Five-vitamin lysine granules and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110227079A CN110227079A (en) | 2019-09-13 |
| CN110227079B true CN110227079B (en) | 2022-07-26 |
Family
ID=67858421
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910482389.0A Active CN110227079B (en) | 2019-06-04 | 2019-06-04 | Five-vitamin lysine granules and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110227079B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114259059B (en) * | 2021-12-09 | 2023-10-20 | 海南金贝康制药有限公司 | Multivitamin calcium zinc chewable tablet and preparation method thereof |
| CN117643576B (en) * | 2024-01-30 | 2024-04-16 | 江西滕王阁药业有限公司 | Preparation method of granules containing lysine hydrochloride and glucose |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1276717A (en) * | 1997-08-22 | 2000-12-13 | 清水制药株式会社 | Glucose-contg. preparation |
| CN104755069A (en) * | 2012-10-31 | 2015-07-01 | 花王株式会社 | Tooth whitening agent |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102888436B (en) * | 2012-09-24 | 2014-06-04 | 天津大学 | Effervescent tablet type low molecular weight collagen peptide and preparation method thereof |
| CN103230593A (en) * | 2012-10-30 | 2013-08-07 | 辽宁亿灵科创生物医药科技有限公司 | Medicine composition used for treating gastrointestinal diseases |
| CN106176756A (en) * | 2015-04-30 | 2016-12-07 | 刘力 | The lysine five comprising chiral photo-isomerisation compound ties up medical composition and its use |
| JP7397563B2 (en) * | 2016-12-28 | 2023-12-13 | 小林製薬株式会社 | solid preparation |
| CN107233305A (en) * | 2017-01-03 | 2017-10-10 | 北京众盈汇丰科技发展有限责任公司 | One kind five ties up lysine oral liquid |
-
2019
- 2019-06-04 CN CN201910482389.0A patent/CN110227079B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1276717A (en) * | 1997-08-22 | 2000-12-13 | 清水制药株式会社 | Glucose-contg. preparation |
| CN104755069A (en) * | 2012-10-31 | 2015-07-01 | 花王株式会社 | Tooth whitening agent |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110227079A (en) | 2019-09-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106420808B (en) | A kind of preparation and preparation method thereof containing vitamin d3 and calcium carbonate | |
| CN110227079B (en) | Five-vitamin lysine granules and preparation method thereof | |
| KR20090094820A (en) | Iron(iii)-carbohydrate based phosphate adsorbent | |
| CN104146197A (en) | Jelly powder for invigorating stomach and improving digestion of infants and preparation method of jelly powder | |
| CN101066244A (en) | Small volume vincamine injection and its prepn process | |
| KR20160110369A (en) | Drug combination, method of preparing same, and use thereof | |
| CN107922513A (en) | A kind of 1,4 oligoglucoses aldehydic acid of oxidized form α and its preparation method and application | |
| CN106389344A (en) | Calcium carbonate particles and preparation method thereof | |
| CN101439076B (en) | Preparation method of chinese medicine granule containing dalbergia heartwood oil | |
| CN113425675A (en) | Calcium zinc gluconate oral solution and preparation method thereof | |
| EP0809995A1 (en) | New diacerhein formulations obtained by active principle inclusion in polysaccharide hydrogels | |
| CN107115325A (en) | Smooth capsules of a kind of butanedioic acid furan Luo Qu and preparation method thereof | |
| CN110279668A (en) | A kind of calcium acetate medications composition and its preparation method and application | |
| CN107550866A (en) | A kind of Sebivo preparation | |
| CN105193844A (en) | Method for preparing delta-hydroxyl contained ferric oxide (multinuclear) and medicine compositions of delta-hydroxyl contained ferric oxide, as well as application to field of hyperphosphatemia | |
| CN1785179A (en) | Compounding chewable vitamin tablets and its prepn. method | |
| CN101439066B (en) | Chinese medicine granular containing notoginseng extract and preparation method thereof | |
| CN1951404A (en) | Oral microemulsion of gingko leaf and preparation method thereof | |
| CN108030767B (en) | Calcitriol injection and preparation method thereof | |
| CN113827570A (en) | Method for preparing traditional Chinese medicine pellet preparation based on drug carrier technology and application thereof | |
| CN101264129A (en) | Sugar-free heart-supplementing dracocephali moldavica granula | |
| CN100402030C (en) | Pharmaceutical composition containing amoxicillin and preparation method thereof | |
| CN107223969A (en) | A kind of ion VC compositions containing blue or green money willow and preparation method thereof | |
| KR20190093999A (en) | Dexibupropen syrup formulation with improved solubility and stability | |
| CN113876727B (en) | Gliclazide sustained release tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 133400 Hexi street, Longjing City, Yanbian Korean Autonomous Prefecture, Jilin Province Patentee after: Grass Immortal Pharmaceutical Co.,Ltd. Address before: 133400 Hexi street, Longjing City, Yanbian Korean Autonomous Prefecture, Jilin Province Patentee before: Yanbian University Herbal Immortal Pharmaceutical Co.,Ltd. |