CN109568287A - Alfacalcidol soft capsule and preparation method thereof - Google Patents
Alfacalcidol soft capsule and preparation method thereof Download PDFInfo
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
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- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
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Abstract
The present invention relates to a kind of Alfacalcidol soft capsules and preparation method thereof.The content of the Alfacalcidol soft capsule is grouped as by the group of following parts by weight: 85-125 parts of oleaginous base, 0.01-0.2 parts of antioxidant, 0.000001-0.000015 parts of Alfacalcidol；The oleaginous base is median chain triglyceride oil.Preparation method includes the following steps: that (1) takes the antioxidant to be sufficiently mixed with the part oleaginous base, obtains mixture；(2) oleaginous base of surplus is poured into inside Agitation Tank, then mixture obtained by step (1) is added to inside the Agitation Tank, is stirred, is uniformly mixed；(3) it is protected from light, the Alfacalcidol is added inside the Agitation Tank, be uniformly mixed under the atmosphere of protective gas, obtain the content of the Alfacalcidol soft capsule；(4) it is protected from light and the content is prepared into soft capsule.The stability of the Alfacalcidol soft capsule is good.
Description
Technical field
The present invention relates to technical field of medicine, more particularly to a kind of Alfacalcidol soft capsule and its preparation side
Method.
Background technique
Soft capsule is made of content and softgel shell, and the ingredient of softgel shell is generally by matrix, plasticizer, preservative, opacifier, color
Element, solvent composition, matrix are generally gelatin, and plasticizer is glycerol, sorbierite, sorbierite etc., and preservative is P-hydroxybenzoic acid
Methyl esters, ethyl-para-hydroxybenzoate, propylparaben, butyl p-hydroxybenzoate, potassium sorbate etc., opacifier two
Titanium oxide, pigment have Kui Lan, and red ferric oxide, manganese dioxide, Black Rouge, amaranth etc., solvent is water.Content composition is general
For drug and solvent.The formulation characteristic determines that the built-in drug of capsule shells is isolated from the outside world, at the same soft capsule have plasticity and
Elasticity, can it is moisture-proof, anti-oxidation, be protected from light, and the stability of drug can be improved, exquisite appearance receives vulnerable to patient.
Alfacalcidol soft capsule is used to treat endogenous 1-25-(OH)2-D3 and generates calcium metabolism caused by deficiency
Disorder disease.Such as renal osteodystrophy, postoperative property or Idiopathic hypoparathyroidsm disease, false parathyroid gland function
It can low disease, the adjuvant treatment as third hyperthyroidism, anti-vitamin D rickets or malacosteon, dimension life
Plain D dependent form rickets, neonatal hypocalcemia disease or the bad disease of rickets, calcium uptake, osteoporosis, malabsorption and battalion
Rickets of nourishing one's nature and malacosteon.
Alfacalcidol stability is poor, although can improve its stabilization after being prepared into soft capsule to a certain extent
Property, but existing Alfacalcidol Stability of Soft Capsules is still not ideal enough, still has that stability is poor, bioavilability is low
Defect.
Summary of the invention
Based on this, the present invention provides a kind of Alfacalcidol soft capsule, the medicine stability of the soft capsule is good.
Specific technical solution is as follows:
A kind of Alfacalcidol soft capsule, content include the component of following parts by weight:
85-125 parts of oleaginous base
0.01-0.2 parts of antioxidant
0.000001-0.000015 parts of Alfacalcidol；
The oleaginous base is median chain triglyceride oil.
In wherein some embodiments, the content of the Alfacalcidol soft capsule includes the component of following parts by weight:
95-115 parts of oleaginous base
0.06-0.15 parts of antioxidant
0.000002-0.000005 parts of Alfacalcidol.
In wherein some embodiments, the content of the Alfacalcidol soft capsule includes the component of following parts by weight:
95-110 parts of oleaginous base
0.08-0.13 parts of antioxidant
0.000002-0.000003 parts of Alfacalcidol.
In wherein some embodiments, the content of the Alfacalcidol soft capsule includes the component of following parts by weight:
105 parts of oleaginous base
0.08 part of antioxidant
0.0000025 part of Alfacalcidol.
In wherein some embodiments, the antioxidant is selected from ascorbyl palmitate, full dl-alpha-tocopherol, 2,
At least one of 6- di-tert-butyl-4-methy phenol and butylated hydroxy anisole.
In wherein some embodiments, the content of the Alfacalcidol soft capsule further includes the group of following parts by weight
Point:
0~50 part of solubilizer, 0~50 part of cosolvent, 0~50 part of preservative, 0~50 part of pH adjusting agent, surfactant 0
~50 parts.
In wherein some embodiments, the solubilizer is selected from polysorbate, polyoxyethylene fatty acid ester, polyoxyethylene rouge
One or more of fat alcohol ether and poloxamer；The cosolvent is selected from glycerol, ethyl alcohol, propylene glycol, polyethylene glycol, poly- second two
One or more of 01 derivatives and ethyl oleate；The preservative be selected from p-hydroxybenzoate, p-hydroxyphenylaceticacid ester,
Para hydroxybenzene propionic ester, para hydroxybenzene butyrate and one or more of benzoic acid and its salt；The pH adjusting agent is selected from cream
Acid, citric acid, malic acid, sodium hydroxide, sodium citrate, sodium carbonate, triethanolamine, sodium hydroxide, sodium bicarbonate, potassium hydroxide
One or more of with magnesium hydroxide；The surfactant is selected from lauryl sodium sulfate, polysorbate, polyoxyethylene rouge
The one or more of fat acid esters, polyoxyethylene aliphatic alcohol ether, poloxamer and polyethyleneglycol derivative.
The present invention also provides the preparation methods of above-mentioned Alfacalcidol soft capsule.The preparation method can effectively improve
The medicine stability of prepared Alfacalcidol soft capsule.
Specific technical solution is as follows:
A kind of preparation method of Alfacalcidol soft capsule, includes the following steps:
(1) it takes the antioxidant to be sufficiently mixed with the part oleaginous base, obtains mixture；
(2) it pours into the oleaginous base of surplus inside Agitation Tank, then mixture obtained by step (1) is added to described
It inside Agitation Tank, stirs, is uniformly mixed；
(3) Alfacalcidol is added inside the Agitation Tank, is uniformly mixed under the atmosphere of protective gas,
Obtain the content of the Alfacalcidol soft capsule；
(4) content is prepared into soft capsule；
Step (3) and step (4) carry out under conditions of being protected from light.
In wherein some embodiments, the part oleaginous base accounts for the 2%-10% of whole oleaginous bases in step (1).
In wherein some embodiments, the revolving speed of stirring described in step (2) is 100-500r/min, and the time of stirring is
5min-30min。
In wherein some embodiments, the revolving speed of stirring described in step (3) is 100-500r/min, and the time of stirring is
1h-3.5h。
In wherein some embodiments, protective gas described in step (3) is nitrogen, and the pressure after being filled with nitrogen is
0.0Mpa-0.5Mpa。
The present inventor is found surprisingly that by lot of experiments: in the content of Alfacalcidol soft capsule
Add specific oleaginous base (median chain triglyceride oil) cooperates the antioxidant of certain dosage that Ah method's bone can be effectively protected again
Change alcohol, greatly improve the stability of Alfacalcidol soft capsule, to guarantee the validity of patient's medication, improves its biological utilisation
Degree.Alfacalcidol soft capsule of the invention, can very effective raising Ah method with extremely simple content formula composition
The stability of ostelin enormously simplifies existing formula composition, and unexpected harvest has arrived ideal stability result,
The problems such as complicated bring safety is formulated due to excipient substance is reduced, the production cost of drug is also reduced.
It is further preferred by being matched to antioxidant, oleaginous base and Alfacalcidol, and to antioxidant type
Further preferably, it can be further improved Alfacalcidol in the stability of soft capsule.
The preparation method of Alfacalcidol soft capsule of the invention, content process for preparation is in protective gas (preferably nitrogen
Gas) protection under carry out, influence of the mixed oxygen to Alfacalcidol stability in whipping process can be effectively reduced.Into one
Part oleaginous base is first uniformly mixed by step ground, preparation method of the invention with antioxidant, adds the oleaginous base of surplus,
Each component in the Alfacalcidol soft capsule of preparation can be made to mix more uniformly, the interaction of each component is improved, into one
Step improves the stability of Alfacalcidol.Preparation method of the invention can effectively improve prepared Alfacalcidol soft capsule
Medicine stability.
By to oleaginous base substep addition amount control and content preparation process in each technological parameter it is excellent
Change, can be further improved Alfacalcidol in the stability of soft capsule.
Specific embodiment
Below by way of specific embodiment, the present invention will be further described in detail.
Number according to the present invention refers both to mass fraction.Not specified percentage generally should understand that in the present invention
It is weight percentage.
Agents useful for same can routinely be bought unless otherwise specified from market in following embodiment.
Embodiment 1
The present embodiment provides a kind of Alfacalcidol soft capsule, content is composed of the following components:
105 parts of median chain triglyceride oil
0.08 part of ascorbyl palmitate
0.0000025 part of Alfacalcidol
The preparation method is as follows:
1. take antioxidant (ascorbyl palmitate) and 8% oleaginous base (median chain triglyceride oil) to be sufficiently mixed,
Obtain mixture.
2. pouring into the oleaginous base of surplus inside Agitation Tank, and 1 gained mixture is added to inside Agitation Tank, then
It stirs 20min (revolving speed 120r/min), is sufficiently mixed.
3. being protected from light, Alfacalcidol is added inside Agitation Tank, under nitrogen (pressure after nitrogen charging is 0.2Mpa) protection
It stirs (revolving speed 120r/min) 1 hour, obtains content.
4. being protected from light, content is put into reservoir, prepares soft capsule using full-automatic encapsulating machine, then wash ball, drying,
It packs up to the Alfacalcidol soft capsule；When washing ball, drying, the soft capsule being pressed into, which is set in cold wind, is formed, and temperature is
18-25 DEG C, humidity 40-50%；Ball to be washed after sizing, sets drying room, temperature is 18-25 DEG C, humidity is 40-50% dry,
To obtain the final product.
Embodiment 2
The present embodiment provides a kind of Alfacalcidol soft capsule, content is composed of the following components:
105 parts of median chain triglyceride oil
0.16 part of ascorbyl palmitate
0.0000025 part of Alfacalcidol
The preparation method is as follows:
1. take antioxidant (ascorbyl palmitate) and 8% oleaginous base (median chain triglyceride oil) to be sufficiently mixed,
Obtain mixture.
2. pouring into the oleaginous base of surplus inside Agitation Tank, and 1 gained mixture is added to inside Agitation Tank, then
It stirs 20min (revolving speed 120r/min), is sufficiently mixed.
3. being protected from light, Alfacalcidol is added inside Agitation Tank, under nitrogen (pressure after nitrogen charging is 0.2Mpa) protection
It stirs (revolving speed 120r/min) 1 hour, obtains content.
4. being protected from light, content is put into reservoir, prepares soft capsule using full-automatic encapsulating machine, then wash ball, drying,
It packs up to the Alfacalcidol soft capsule；When washing ball, drying, the soft capsule being pressed into, which is set in cold wind, is formed, and temperature is
18-25 DEG C, humidity 40-50%；Ball to be washed after sizing, sets drying room, temperature is 18-25 DEG C, humidity is 40-50% dry,
To obtain the final product.
Embodiment 3
The present embodiment provides a kind of Alfacalcidol soft capsule, content is composed of the following components:
105 parts of median chain triglyceride oil
0.04 part of ascorbyl palmitate
0.0000025 part of Alfacalcidol
The preparation method is as follows:
1. take antioxidant (ascorbyl palmitate) and 8% oleaginous base (median chain triglyceride oil) to be sufficiently mixed,
Obtain mixture.
2. pouring into the oleaginous base of surplus inside Agitation Tank, and 1 gained mixture is added to inside Agitation Tank, then
It stirs 20min (revolving speed 120r/min), is sufficiently mixed.
3. being protected from light, Alfacalcidol is added inside Agitation Tank, under nitrogen (pressure after nitrogen charging is 0.2Mpa) protection
It stirs (revolving speed 120r/min) 1 hour, obtains content.
4. being protected from light, content is put into reservoir, prepares soft capsule using full-automatic encapsulating machine, then wash ball, drying,
It packs up to the Alfacalcidol soft capsule；When washing ball, drying, the soft capsule being pressed into, which is set in cold wind, is formed, and temperature is
18-25 DEG C, humidity 40-50%；Ball to be washed after sizing, sets drying room, temperature is 18-25 DEG C, humidity is 40-50% dry,
To obtain the final product.
Embodiment 4
The present embodiment provides a kind of Alfacalcidol soft capsule, content is composed of the following components:
105 parts of median chain triglyceride oil
0.04 part of 2,6- di-tert-butyl-4-methy phenols (BHT)
0.0000025 part of Alfacalcidol
The preparation method is as follows:
1. antioxidant (BHT) and 8% oleaginous base (median chain triglyceride oil) is taken to be sufficiently mixed, mixture is obtained.
2. pouring into the oleaginous base of surplus inside Agitation Tank, and 1 gained mixture is added to inside Agitation Tank, then
It stirs 20min (revolving speed 120r/min), is sufficiently mixed；
3. being protected from light, Alfacalcidol is added inside Agitation Tank, under nitrogen (pressure after nitrogen charging is 0.3Mpa) protection
It stirs (revolving speed 120r/min) 1 hour, obtains content.
4. being protected from light, content is put into reservoir, prepares soft capsule using full-automatic encapsulating machine, then wash ball, drying,
It packs up to the Alfacalcidol soft capsule；When washing ball, drying, the soft capsule being pressed into, which is set in cold wind, is formed, and temperature is
18-25 DEG C, humidity 40-50%；Ball to be washed after sizing, sets drying room, temperature is 18-25 DEG C, humidity is 40-50% dry,
To obtain the final product.
Embodiment 5
The present embodiment provides a kind of Alfacalcidol soft capsule, content is composed of the following components:
105 parts of median chain triglyceride oil
0.04 part of butylated hydroxy anisole (BHA)
0.04 part of 2,6- di-tert-butyl-4-methy phenols (BHT)
0.0000025 part of Alfacalcidol
The preparation method is the same as that of Example 1.
Embodiment 6
The present embodiment provides a kind of Alfacalcidol soft capsule, content is composed of the following components:
105 parts of median chain triglyceride oil
0.08 part of ascorbyl palmitate
0.0000025 part of Alfacalcidol
The preparation method is as follows:
1. antioxidant (ascorbyl palmitate) and 0.5% oleaginous base (median chain triglyceride oil) is taken sufficiently to mix
It closes, obtains mixture.
2. pouring into the oleaginous base of surplus inside Agitation Tank, and 1 gained mixture is added to inside Agitation Tank, then
It stirs 20min (revolving speed 120r/min), is sufficiently mixed.
3. being protected from light, Alfacalcidol is added inside Agitation Tank, under nitrogen (pressure after nitrogen charging is 0.2Mpa) protection
It stirs (revolving speed 120r/min) 1 hour, obtains content.
4. being protected from light, content is put into reservoir, prepares soft capsule using full-automatic encapsulating machine, then wash ball, drying,
It packs up to the Alfacalcidol soft capsule；When washing ball, drying, the soft capsule being pressed into, which is set in cold wind, is formed, and temperature is
18-25 DEG C, humidity 40-50%；Ball to be washed after sizing, sets drying room, temperature is 18-25 DEG C, humidity is 40-50% dry,
To obtain the final product.
Embodiment 7
The present embodiment provides a kind of Alfacalcidol soft capsule, content is composed of the following components:
105 parts of median chain triglyceride oil
0.08 part of ascorbyl palmitate
0.0000025 part of Alfacalcidol
The preparation method is as follows:
1. take antioxidant (ascorbyl palmitate) and 20% oleaginous base (median chain triglyceride oil) to be sufficiently mixed,
Obtain mixture.
2. pouring into the oleaginous base of surplus inside Agitation Tank, and 1 gained mixture is added to inside Agitation Tank, then
It stirs 20min (revolving speed 120r/min), is sufficiently mixed.
3. being protected from light, Alfacalcidol is added inside Agitation Tank, under nitrogen (pressure after nitrogen charging is 0.2Mpa) protection
It stirs (revolving speed 120r/min) 1 hour, obtains content.
4. being protected from light, content is put into reservoir, prepares soft capsule using full-automatic encapsulating machine, then wash ball, drying,
It packs up to the Alfacalcidol soft capsule；When washing ball, drying, the soft capsule being pressed into, which is set in cold wind, is formed, and temperature is
18-25 DEG C, humidity 40-50%；Ball to be washed after sizing, sets drying room, temperature is 18-25 DEG C, humidity is 40-50% dry,
To obtain the final product.
Comparative example 1
This comparative example provides a kind of Alfacalcidol soft capsule, and content is composed of the following components:
105 parts of median chain triglyceride oil
0.0000025 part of Alfacalcidol
1. pouring into oleaginous base (median chain triglyceride oil) inside Agitation Tank.
3. being protected from light, Alfacalcidol is added inside Agitation Tank, under nitrogen (pressure after nitrogen charging is 0.2Mpa) protection
It stirs (revolving speed 120r/min) 1 hour, obtains content.
3. being protected from light, content is put into reservoir, soft capsule is prepared using full-automatic encapsulating machine, then washes ball, drying, packet
It fills up to the Alfacalcidol soft capsule；When washing ball, drying, the soft capsule being pressed into, which is set in cold wind, is formed, temperature 18-
25 DEG C, humidity 40-50%；Washed ball after sizing, set drying room, temperature is 18-25 DEG C, humidity be 40-50% it is dry to get.
Comparative example 2
This comparative example provides a kind of Alfacalcidol soft capsule, and content is composed of the following components:
105 parts of sesame oil
0.08 part of ascorbyl palmitate
0.0000025 part of Alfacalcidol
The preparation method is the same as that of Example 1.
Comparative example 3
This comparative example provides a kind of Alfacalcidol soft capsule, and content is composed of the following components:
105 parts of median chain triglyceride oil
0.08 part of ascorbyl palmitate
0.0000025 part of Alfacalcidol
The preparation method is as follows:
1. take antioxidant (ascorbyl palmitate) and 8% oleaginous base (median chain triglyceride oil) to be sufficiently mixed,
Obtain mixture.
2. pouring into the oleaginous base of surplus inside Agitation Tank, and 1 gained mixture is added to inside Agitation Tank, then
It stirs 20min (revolving speed 120r/min), is sufficiently mixed.
3. being protected from light, Alfacalcidol is added inside Agitation Tank, stirs (revolving speed 120r/min) 1 hour (not nitrogen charging),
Obtain content.
4. being protected from light, content is put into reservoir, soft capsule is prepared using full-automatic encapsulating machine, then washes ball, drying, packet
It fills up to the Alfacalcidol soft capsule；When washing ball, drying, the soft capsule being pressed into, which is set in cold wind, is formed, temperature 18-25
DEG C, humidity 40-50%；Washed ball after sizing, set drying room, temperature is 18-25 DEG C, humidity be 40-50% it is dry to get.
8 stability experiment of embodiment
According to 2015 editions Chinese Pharmacopoeias, four general rule guidelines 9001, " material medicine and preparation stability test direction are former
Then " carry out accelerated stability investigation.Sample is in 40 DEG C of temperature, the lower placement of relative humidity 75% 6 months, respectively at 0,1,3 and 6
The indexs such as character, content, disintegration time limited, microbial limit, the related substance of each group sample are detected when the moon after sampling, each index
The regulation of detection method 2015 editions Chinese Pharmacopoeias of reference, wherein related substance is according to 2015 editions Chinese Pharmacopoeias, two Alfacalcidols
The content assaying method of soft capsule quality standard is detected, 100 μ l of sampling volume.
Testing result is as shown in table 1.
Table 1
From experimental result: the stability of Alfacalcidol soft capsule prepared by embodiment 1-7 is better than comparative example 1-
3, it is seen that particular kind of oleaginous base is selected to cooperate a certain amount of antioxidant that can greatly improve Alfacalcidol in soft capsule
In medicine stability, and nitrogen charging can be further improved the medicine stability of obtained soft capsule during the preparation process；
Wherein the stability of the Alfacalcidol soft capsule of embodiment 1-5 is more preferable, is less susceptible to decompose generation impurity, illustrate in preparation process
Part oleaginous base is uniformly mixed with antioxidant first, adds the oleaginous base of surplus, and the oiliness that substep is added
The amount control of matrix in a certain range, can be further improved the stability of Alfacalcidol, be due to operating in this way
Each component in the Alfacalcidol soft capsule of preparation can be made to mix more uniformly, improve the interaction of each component, in turn
The coordinative role of each component can more fully be played；Further, the type for the raw material components that wherein embodiment 1 uses and match
Than the most rationally, the sample of preparation is most stable.
Each technical characteristic of embodiment described above can be combined arbitrarily, for simplicity of description, not to above-mentioned reality
It applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, all should be considered as described in this specification.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
It cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the art
It says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to protection of the invention
Range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (10)
1. a kind of Alfacalcidol soft capsule, which is characterized in that its content includes the component of following parts by weight:
85-125 parts of oleaginous base
0.01-0.2 parts of antioxidant
0.000001-0.000015 parts of Alfacalcidol；
The oleaginous base is median chain triglyceride oil.
2. Alfacalcidol soft capsule according to claim 1, which is characterized in that its content includes following parts by weight
Component:
95-115 parts of oleaginous base
0.06-0.15 parts of antioxidant
0.000002-0.000005 parts of Alfacalcidol.
3. Alfacalcidol soft capsule according to claim 2, which is characterized in that its content includes following parts by weight
Component:
95-110 parts of oleaginous base
0.08-0.13 parts of antioxidant
0.000002-0.000003 parts of Alfacalcidol.
4. Alfacalcidol soft capsule according to claim 3, which is characterized in that its content includes following parts by weight
Component:
105 parts of oleaginous base
0.08 part of antioxidant
0.0000025 part of Alfacalcidol.
5. Alfacalcidol soft capsule according to claim 1-4, which is characterized in that the antioxidant is selected from anti-
In bad hematic acid palmitate, full dl-alpha-tocopherol, 2,6- di-tert-butyl-4-methy phenol and butylated hydroxy anisole extremely
Few one kind.
6. Alfacalcidol soft capsule according to claim 1-4, which is characterized in that its content further include as
The component of lower parts by weight: 0~50 part of solubilizer, 0~50 part of cosolvent, 0~50 part of preservative, 0~50 part of pH adjusting agent, surface
0~50 part of activating agent；
The solubilizer in polysorbate, polyoxyethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether and poloxamer one
Kind is several；The cosolvent is in glycerol, ethyl alcohol, propylene glycol, polyethylene glycol, polyethyleneglycol derivative and ethyl oleate
It is one or more of；The preservative be selected from p-hydroxybenzoate, p-hydroxyphenylaceticacid ester, para hydroxybenzene propionic ester, to hydroxyl
Benzenebutanoic acid ester and one or more of benzoic acid and its salt；The pH adjusting agent is selected from lactic acid, citric acid, malic acid, hydrogen-oxygen
Change one of sodium, sodium citrate, sodium carbonate, triethanolamine, sodium hydroxide, sodium bicarbonate, potassium hydroxide and magnesium hydroxide or
It is several；The surfactant is selected from lauryl sodium sulfate, polysorbate, polyoxyethylene fatty acid ester, Polyoxyethylene fatty
The one or more of alcohol ether, poloxamer and polyethyleneglycol derivative.
7. the preparation method of Alfacalcidol soft capsule described in any one of claims 1-6, which is characterized in that including walking as follows
It is rapid:
(1) it takes the antioxidant to be sufficiently mixed with the part oleaginous base, obtains mixture；
(2) it pours into the oleaginous base of surplus inside Agitation Tank, then mixture obtained by step (1) is added to described with liquid
It inside tank, stirs, is uniformly mixed；
(3) Alfacalcidol is added inside the Agitation Tank, is uniformly mixed under the atmosphere of protective gas, obtains institute
State the content of Alfacalcidol soft capsule；
(4) content is prepared into soft capsule；
Step (3) and step (4) carry out under conditions of being protected from light.
8. the preparation method of Alfacalcidol soft capsule according to claim 7, which is characterized in that part in step (1)
The oleaginous base accounts for the 2%-10% of whole oleaginous bases.
9. the preparation method of Alfacalcidol soft capsule according to claim 7, which is characterized in that described in step (2)
The revolving speed of stirring is 100-500r/min, and the time of stirring is 5min-30min；And/or
The revolving speed of stirring described in step (3) is 100-500r/min, and the time of stirring is 1h-3.5h.
10. according to the preparation method of the described in any item Alfacalcidol soft capsules of claim 7-9, which is characterized in that step
(3) protective gas described in is nitrogen, and the pressure after being filled with nitrogen is 0.0Mpa-0.5Mpa.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111214453A (en) * | 2020-03-06 | 2020-06-02 | 广州白云山星群(药业)股份有限公司 | Alfacalcidol soft capsule and preparation method thereof |
| CN111588696A (en) * | 2020-04-28 | 2020-08-28 | 南通华山药业有限公司 | Alfacalcidol oral liposome medicine and preparation method and application thereof |
| CN116270520A (en) * | 2023-03-03 | 2023-06-23 | 正大制药（青岛）有限公司 | Vitamin D capsule type drop and preparation method thereof |
| CN118252813A (en) * | 2024-05-30 | 2024-06-28 | 青松医药集团股份有限公司 | Alfacalcidol soft capsule and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH054925A (en) * | 1991-06-27 | 1993-01-14 | Teikoku Chem Ind Corp Ltd | Soft capsule preparation of alpha calcidiol |
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2019
- 2019-01-16 CN CN201910039540.3A patent/CN109568287A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH054925A (en) * | 1991-06-27 | 1993-01-14 | Teikoku Chem Ind Corp Ltd | Soft capsule preparation of alpha calcidiol |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111214453A (en) * | 2020-03-06 | 2020-06-02 | 广州白云山星群(药业)股份有限公司 | Alfacalcidol soft capsule and preparation method thereof |
| CN111214453B (en) * | 2020-03-06 | 2021-04-13 | 广州白云山星群(药业)股份有限公司 | Alfacalcidol soft capsule and preparation method thereof |
| CN111588696A (en) * | 2020-04-28 | 2020-08-28 | 南通华山药业有限公司 | Alfacalcidol oral liposome medicine and preparation method and application thereof |
| CN116270520A (en) * | 2023-03-03 | 2023-06-23 | 正大制药（青岛）有限公司 | Vitamin D capsule type drop and preparation method thereof |
| CN118252813A (en) * | 2024-05-30 | 2024-06-28 | 青松医药集团股份有限公司 | Alfacalcidol soft capsule and preparation method thereof |
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