CN107875134A - paricalcitol liquid hard capsule and preparation method thereof - Google Patents
paricalcitol liquid hard capsule and preparation method thereof Download PDFInfo
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- CN107875134A CN107875134A CN201711062041.3A CN201711062041A CN107875134A CN 107875134 A CN107875134 A CN 107875134A CN 201711062041 A CN201711062041 A CN 201711062041A CN 107875134 A CN107875134 A CN 107875134A
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- paricalcitol
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- hard capsule
- antioxidant
- lower alcohol
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- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
- A61K9/4825—Proteins, e.g. gelatin
-
- 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
- A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
Abstract
The present invention relates to pharmaceutical field, and in particular to a kind of paricalcitol liquid hard capsule and preparation method thereof.Paricalcitol liquid hard capsule mainly utilizes hard capsule case parcel paricalcitol pharmaceutical composition.In parts by weight, paricalcitol pharmaceutical composition is mainly made up of 0.25 4 parts of paricalcitols, 720 1500 parts of lower alcohol solvents, 50,000 290000 parts of oleaginous bases and 8 20 parts of antioxidant.The capsule agent content uniformity is good, steady quality, long shelf-life and bioavilability are high.
Description
Technical field
The present invention relates to pharmaceutical field, and in particular to a kind of paricalcitol liquid hard capsule and preparation method thereof.
Background technology
Vitamin D is a kind of liposoluble vitamin.Two kinds of critically important forms are in people：Vitamin D2 (vitamin
D2) and cholecalciferol (vitamin D3).Vitamin D325 (OH) D are converted into liver3。25(OH)D3By hepatic transport to kidney
It is dirty, and through 25-hydroxy-vitamin D31The hydroxylation of-hydroxylase forms active hormones paricalcitol.The activity form is with depositing
Combined in the vitamin D receptor (VDR) in parathyroid gland, intestines, kidney and bone to maintain the dynamic of parathyroid function and calcium and phosphorus
State is balanced, and VDR is also present in many other tissues, including prostate, endothelium and immunocyte.VDR activation is to normal bone
Be suitably formed and maintenance is necessary.In the kidney of lesion, the activation of vitamin D reduces, and causes parathyroid hormone to rise,
Subsequently result in the disturbance of the dynamic equilibrium of Secondary cases parathyropathy (secondary arathyroidism) and calcium and phosphorus.
Paricalcitol is novel vitamin D analogues, can effectively suppress parathyroid hormone (PTH) level.It is usually used in chronic
Secondary hyperparathyroidism (secondary hyperparathyroidismin) SHPT of patients with renal failure
Prevention and treatment.
Chinese patent CN102772364B discloses the Fat Emulsion and its preparation and preparation method of a kind of paricalcitol.Place
Without using organic solvent, stimulation of the reduction used for intravenous injection to blood vessel in side, but emulsifying agent is used, there is certain physiology poison
Property, and injection administration is inconvenient.Emulsification acquires a certain degree of difficulty again after freeze-dried emulsion and capsule developing agent storage.
Chinese patent CN103893114A discloses a kind of Vitamin D receptor agonist drug regimen of the injectable of stabilization
Thing and preparation method thereof.Paricalcitol injection is prepared, contains nonionic solubilizer, organic solvent, water in component.During administration
Organic solvent has certain excitant, drug administration by injection, patient's poor compliance to blood vessel.
The A of Chinese patent CN 104162168 disclose a kind of paricalcitol cyclodextrin inclusion compound drug regimen and its
Prepare.After paricalcitol is made into cyclodextrin inclusion compound, adds stabilizer and prepare freeze-dried powder, mixed with other auxiliary materials, used
Dry granulation technology prepares oral solid formulation.Cyclodextrin inclusion compound bag and rate are difficult to control, and it is poor not include raw material stability.
Chinese patent CN106265492A discloses a kind of drug regimen and preparation method of paricalcitol injection, group
Contain nonionic solubilizer, organic solvent, water in point.Control remaining oxygen increase medicine storage stability in ampoule bottle.Preparation group
Into similar to patent CN103893114A, prescription contains organic solvent, easily causes injection site pain when injecting blood vessel.And injection
In-convenience in use patient's poor compliance.
Paricalcitol is not soluble in water, solvable in most polar solvents.Moist with drawing, unstable chemcial property is right
PH, oxygen are more sensitive.
Existing paricalcitol listing formulation includes injection, and main ingredient is dissolved in organic solvent and be made, gives by injection
Organic solvent has certain excitant to blood vessel during medicine.And injection in-convenience in use, patient's poor compliance.
Therefore, develop that a kind of uniformity of dosage units is good, quality is more stable, pa convenient to take and cheap cost is vertical ossified
Alcohol formulations are particularly important.
In view of this, it is special to propose the present invention.
The content of the invention
It is an object of the invention to provide a kind of paricalcitol liquid hard capsule, the capsule agent content uniformity is good,
Steady quality, long shelf-life and bioavilability are high.
Another object of the present invention is to provide a kind of preparation method of paricalcitol liquid hard capsule, technical process
Simply, operating condition readily satisfies, and operating procedure linking is close, and technological parameter is easily-controllable, and no waste produces, production process green ring
Protect.
The present invention is solved its technical problem and realized using following technical scheme：
The present invention proposes a kind of paricalcitol liquid hard capsule, and it mainly uses the filling paricalcitol of hard capsule case
Pharmaceutical composition.In parts by weight, paricalcitol pharmaceutical composition is mainly by 0.25-4 part paricalcitols, 720-1500
Part lower alcohol solvent, 50000-290000 parts oleaginous base and 8-20 part antioxidant are made.
The present invention proposes a kind of preparation method of paricalcitol liquid hard capsule, comprises the following steps：With parts by weight
Meter, by 0.25-4 parts paricalcitol, 8-20 parts antioxidant and 720-1500 parts lower alcohol solvent mix after again with 50000-
It is filling in hard capsule case after 290000 parts of oleaginous base mixing.
The beneficial effect of paricalcitol liquid hard capsule of the present invention and preparation method thereof is：Invention provides a kind of pa
Vertical ostelin liquid hard capsule, which obviate in the prior art to improve medicine stability in itself and dissolubility addition
The defects of substantial amounts of auxiliary material, formula of the invention is simple but drug solubility and stability are all good, without additionally adding it
His solubilizing auxiliary materials.Better stability of preparation, the content of active ingredient is guaranteed, is not had under aging and content in storage process
The phenomenon of drop occurs.It is convenient for carrying, it is convenient to take.The preparation technology of the present invention is simple, and easy to operate, technological parameter is easily-controllable, raw
Production process is green, virtually also reduces production cost, and reduce manpower and materials supporting in production process into
This.
Embodiment
, below will be in the embodiment of the present invention to make the purpose, technical scheme and advantage of the embodiment of the present invention clearer
Technical scheme be clearly and completely described.Unreceipted actual conditions person, builds according to normal condition or manufacturer in embodiment
The condition of view is carried out.Agents useful for same or the unreceipted production firm person of instrument, it is the conventional production that can be obtained by commercially available purchase
Product.
In the description of the invention, it is necessary to which explanation, term " first ", " second " etc. are only used for distinguishing description, without
It is understood that to indicate or implying relative importance.
Paricalcitol liquid hard capsule of the embodiment of the present invention and preparation method thereof is specifically described below.
A kind of paricalcitol liquid hard capsule provided in an embodiment of the present invention, it mainly uses the filling original of hard capsule case
Auxiliary material mixed solution.It can effectively prevent gelatin to be crosslinked aging using hard capsule case is filling, then ensure capsules break and medicine
The time of dissolution, ensure the quality and stability of product.
Further, hard capsule case is HPMC Capsuleses or gelatin hollow capsule.Above two capsule shells and material phase
Capacitive is good, and stability is high, cheap, therefore preferably both hard capsule cases can effectively prevent paricalcitol liquid hard
Wafer goes bad, and then ensures the rupture of capsule, and medicine is readily absorbed by.HPMC Capsuleses are the hollow glue of HPMC
Capsule has good pliability, and moisture content is low, strong to environmental suitability, can effectively ensure that paricalcitol liquid hard capsule
The drug effect of agent.
Further, in parts by weight, paricalcitol pharmaceutical composition is mainly by 0.25-4 part paricalcitols,
720-1500 part lower alcohol solvents, 50000-290000 parts oleaginous base and 8-20 part antioxidant are made.Preferably, pa is vertical ossified
Alcohol pharmaceutical composition is mainly by 1-3 part paricalcitols, 800-1200 part lower alcohol solvents, 100000-250000 part oiliness
Matrix and 10-18 part antioxidant are made, it is highly preferred that paricalcitol pharmaceutical composition is mainly vertical ossified by 2-2.5 parts pa
Alcohol, 900-1000 part lower alcohol solvents, 150000-200000 parts oleaginous base and 12-15 part antioxidant are made.Above-mentioned each original
Material can ensure that paricalcitol has good solubility in paricalcitol liquid hard capsule using aforementioned proportion, and protect
Card paricalcitol is dispersed in paricalcitol liquid hard capsule, is improved in paricalcitol liquid hard capsule
The uniformity of dosage units of paricalcitol, ensure that paricalcitol liquid hard capsule has good stability.
Further, lower alcohol solvent is monohydric alcohol, it is preferable that lower alcohol solvent is absolute ethyl alcohol, propyl alcohol or butanol
One or more.Dissolving Paricalcitol is easy in a solvent using above-mentioned polar solvent, then lifts paricalcitol
Solubility, and paricalcitol has good stability in above-mentioned polar solvent.
Further, oleaginous base includes MCT Oil, vegetable oil or isopropyl ester type compound, preferably
Ground, vegetable oil be coconut oil, castor oil or soybean oil in one kind, isopropyl ester type compound be isopropyl myristate or
Isopropyl palmitate, it is further preferred that oleaginous base is MCT Oil or coconut oil.Oleaginous base can either effectively be prevented
Only air contacts with paricalcitol, while is beneficial to absorption of the human body to paricalcitol.MCT Oil is referred to as
MCT, it is a kind of saturated fatty acid, its freezing point is low, is at room temperature liquid, viscosity is small.And MCT Oil has
Antibacterial ability, pathogenic bacteria can be killed, lift the security of paricalcitol, reduce side effect.Coconut oil is by coconut meat (dry)
Obtain, for white or faint yellow fat, wherein coconut oil is the grease being uniquely made up of in our conventional foods medium chain fatty acid.
Castor oil is the glyceryl ester of aliphatic acid, and castor oil is present in the seed of castor-oil plant, and its content is 35%~57%
With squeeze or solvent extraction be made castor oil.Castor oil is soluble in ethanol, then enables castor oil vertical ossified with pa
Alcohol liquid hard capsule others raw material is well mixed, and lifts the drug effect of paricalcitol liquid hard capsule.Soybean oil is from big
One kind oil that squeezing extracts in beans, generally we term it " soybean salad oil ", soybean oil contains palmitic acid, oleic acid, hard
Resin acid, linoleic acid, arachidic acid and leukotrienes.The dissolving that soybean oil can not only increase paricalcitol is also prevented from pa and stood
Ostelin aoxidizes, and then ensures the stability of medicine in paricalcitol liquid hard capsule.
Isopropyl myristate has good performance of keeping humidity, and is easily absorbed by the body, and is easy to active ingredient to enter people
Body.Isopropyl palmitate to be colourless to pale yellow oily liquid, it is not volatile, it is flammable, have micro- grease taste.Ethanol, second can be dissolved in
The organic solvents such as ether, it is impossible to be dissolved in water and glycerine, have permeability to skin.Help to be lifted the stability of paricalcitol and molten
Xie Xing, it is uniformly dispersed beneficial to paricalcitol in paricalcitol liquid hard capsule.
Further, antioxidant is dibutyl hydroxy toluene or butylated hydroxy anisole.Dibutyl hydroxy toluene, also known as 2,
6- BHTs, abbreviation BHT, the antioxidation of dibutyl hydroxy toluene be due to its own occur autoxidation and
Realize, BHT stability is high, and oxidation resistance is strong, and does not interfere with the drug effect of paricalcitol.Butylated hydroxy anisole, again
Name tertiary butyl-4-hydroxy anisole, butyl hydroxy anisol, abbreviation BHA, the antioxidation of butylated hydroxy anisole is put by it
Go out hydrogen atom to block grease autoxidation and realize, it can effectively prevent the oxidation of active ingredient, while not interfere with
Imitate the drug effect of composition.
The present invention also provides a kind of preparation method of paricalcitol liquid hard capsule；
In parts by weight, by 0.25-4 parts paricalcitol, 8-20 parts antioxidant and 720-1500 part lower alcohol solvents
It is filling in hard capsule case after being mixed again with 50000-290000 part oleaginous bases after mixing.
Specifically, it is dissolved in by antioxidant in lower alcohol solvent, paricalcitol is then added into antioxidant again
In the mixture of lower alcohol solvent.First addition antioxidant can prevent paricalcitol from oxygen occurs after adding lower alcohol solvent
Change acts on so that paricalcitol can be protected at once when adding lower alcohol solvent, then ensure the drug effect of paricalcitol.
Then the mixture of above-mentioned substance is added in oleaginous base again, the larger oiliness of the said mixture amount of being added to
In matrix, oleaginous base quickly can be disperseed above-mentioned mixing, can be avoided in the prior art to improve medicine in itself
Stability and dissolubility and largely add various auxiliary materials, the embodiment of the present invention both can be with only with antioxidant and oleaginous base
The stability and dissolubility of medicine are protected, and without additionally adding other solubilizing auxiliary materials.
Further, by the mixture of paricalcitol, antioxidant and lower alcohol solvent at the temperature below 25 DEG C
Mixed with oleaginous base.It can ensure paricalcitol liquid hard capsule in preparation process below 25 DEG C temperature control
Stability.
Further, it is the mixture of paricalcitol, antioxidant, lower alcohol solvent and oleaginous base is filling in ebonite
Vacuumize process is carried out to mixture before softgel shell.Application of vacuum excludes air existing for solution, prevents paricalcitol liquid
There is air in hard capsule, then can effectively prevent the quality of paricalcitol from changing, then lift paricalcitol
The drug effect and stability of liquid hard capsule.
It is then that solution is filling in hard capsule case, and encapsulate pharmaceutical coating material in the suit place of hard capsule case.Capsule
The upper pharmaceutical coating material of suit place encapsulating, built-in medicine is in the state of relative insulation with outside air, further keep away
The moisture absorption of built-in medicine is exempted from or has been oxidized.
Invention gained paricalcitol liquid hard capsule, paricalcitol is dissolved in oleaginous base with molecular state,
The problem of overcoming drug solubility difference stability of solution difference, medicaments uniformity is scattered in liquid excipient, improves medicine
Uniformity of dosage units.Reperfu- sion has completely cut off contact of the medicine with air/water point in hard capsule case, adds the stability of medicine.
The present invention has arranged in pairs or groups more excellent antioxidant and oleaginous base, avoids in the prior art to improve medicine steady in itself
Qualitative and dissolubility adds the defects of substantial amounts of auxiliary material.The formula of the present invention is simple but dissolubility and stability are all good,
Without additionally adding other solubilizing auxiliary materials, dosage form stability is high, and the content of active ingredient is guaranteed, is not had in storage process
The phenomenon that aging and content decline occurs.It is convenient for carrying, it is convenient to take.
The feature and performance of the present invention are described in further detail with reference to embodiments.
Embodiment 1
The present embodiment provides a kind of paricalcitol liquid hard capsule, and it is mainly vertical ossified using the filling pa of hard capsule case
Alcohol pharmaceutical composition.Wherein, paricalcitol pharmaceutical composition is mainly by 1 part of paricalcitol, 800 parts of absolute ethyl alcohols, 10 parts
Dibutyl hydroxy toluene, 100000 parts of MCT Oils are made.
The present invention also provides a kind of method for preparing paricalcitol liquid hard capsule, and dibutyl hydroxy toluene is added
In absolute ethyl alcohol, after stirring and dissolving, paricalcitol, stirring and dissolving are added.Chain fat during solution containing paricalcitol is added
In fat acid glycerol three ester, it is uniformly mixed.Degassing is vacuumized, is poured into hard capsule case, and is encapsulated in the suit place of capsule
Upper pharmaceutical coating material.
Embodiment 2
The present embodiment provides a kind of paricalcitol liquid hard capsule, and it is mainly vertical ossified using the filling pa of hard capsule case
Alcohol pharmaceutical composition.Wherein, paricalcitol pharmaceutical composition is mainly by 4 parts of paricalcitols, 1500 parts of propyl alcohol, 20 parts of butyl
BHA, 290000 portions of coconut oil are made.
The present invention also provides a kind of method for preparing paricalcitol liquid hard capsule, and butylated hydroxy anisole is added
In propyl alcohol, after stirring and dissolving, paricalcitol, stirring and dissolving are added.Solution containing paricalcitol is added in coconut oil system,
It is uniformly mixed.Degassing is vacuumized, is poured into hard capsule case, and the pharmaceutical coating material in the encapsulating of the suit place of capsule.
Embodiment 3
The present embodiment provides a kind of paricalcitol liquid hard capsule, and it is mainly vertical ossified using the filling pa of hard capsule case
Alcohol pharmaceutical composition.Wherein, paricalcitol pharmaceutical composition is mainly by 0.25 part of paricalcitol, 750 parts of butanol, 8 parts of fourths
Base BHA, 50000 parts of isopropyl myristates are made.
The present invention also provides a kind of method for preparing paricalcitol liquid hard capsule, and butylated hydroxy anisole is added
In butanol, after stirring and dissolving, paricalcitol, stirring and dissolving are added.It is different that solution containing paricalcitol is added into myristic acid
In propyl ester, it is uniformly mixed.Degassing is vacuumized, is poured into hard capsule case, and the medicinal bag in the encapsulating of the suit place of capsule
Clothing material.
Embodiment 4
The present embodiment provides a kind of paricalcitol liquid hard capsule, and it is mainly vertical ossified using the filling pa of hard capsule case
Alcohol pharmaceutical composition.Wherein, paricalcitol pharmaceutical composition is mainly by 3 parts of paricalcitols, 1200 parts of absolute ethyl alcohols, 18 parts
Dibutyl hydroxy toluene, 250000 parts of isopropyl palmitates are made.
The present invention also provides a kind of method for preparing paricalcitol liquid hard capsule, and dibutyl hydroxy toluene is added
In absolute ethyl alcohol, after stirring and dissolving, paricalcitol, stirring and dissolving are added.Solution containing paricalcitol is added into palmitic acid
In isopropyl ester, it is uniformly mixed.Degassing is vacuumized, is poured into hard capsule case, and it is medicinal in the encapsulating of the suit place of capsule
Coating material.
Embodiment 5
The present embodiment provides a kind of paricalcitol liquid hard capsule, and it is mainly vertical ossified using the filling pa of hard capsule case
Alcohol pharmaceutical composition.Wherein, paricalcitol pharmaceutical composition is mainly by 2 parts of paricalcitols, 900 parts of absolute ethyl alcohols, 12 parts
Dibutyl hydroxy toluene, 150000 parts of castor oil are made.
The present invention also provides a kind of method for preparing paricalcitol liquid hard capsule, and dibutyl hydroxy toluene is added
In absolute ethyl alcohol, after stirring and dissolving, paricalcitol, stirring and dissolving are added.Solution containing paricalcitol is added into castor oil
In, it is uniformly mixed.Degassing is vacuumized, is poured into hard capsule case, and the medical coating material in the encapsulating of the suit place of capsule
Material.
Embodiment 6
The present embodiment provides a kind of paricalcitol liquid hard capsule, and it is mainly vertical ossified using the filling pa of hard capsule case
Alcohol pharmaceutical composition.Wherein, paricalcitol pharmaceutical composition is mainly by 2.5 parts of paricalcitols, 1000 parts of propyl alcohol, 15 parts of fourths
Base BHA, 200000 portions of soybean oils are made.
The present invention also provides a kind of method for preparing paricalcitol liquid hard capsule, and butylated hydroxy anisole is added
In propyl alcohol, after stirring and dissolving, paricalcitol, stirring and dissolving are added.Solution containing paricalcitol is added in soybean oil, stirred
Mix well mixed.Degassing is vacuumized, is poured into hard capsule case, and the pharmaceutical coating material in the encapsulating of the suit place of capsule.
Experimental example 1
By 1-6 of the embodiment of the present invention and external commercially available soft capsule preparation (specification：1 μ g) according to version Chinese Pharmacopoeia four in 2015
Portion's general rule guideline 9001 " material medicine and preparation stability test direction principle " progress long-time stability (25 DEG C of temperature ±
2 DEG C, relative humidity 60% ± 10%) to investigate, stability high spot reviews project is content and relevant material, dissolution situation.And point
Sampling carries out content, dissolution rate and relevant material using HPLC methods not when 0,3,6,9,12,18,24 and 36 months.
Assay chromatographic condition：Chromatographic column：Octadecyl silane post (250mm × 4.6mm, 5 μm), mobile phase：
Methanol-water (4:1), Detection wavelength：252nm, flow velocity：2ml/min, sample size：100μl.The preparation of reference substance solution：Pa is taken to stand
Ostelin reference substance is appropriate, and the solution for containing 2.0 μ g in every 1ml is made of flowing phased soln and dilution, shakes up, produces.Containing measurement
Determine method：Take sample contents appropriate, it is accurately weighed, it is made with flowing phased soln and dilution in every 1ml containing about 2 μ g solution,
As need testing solution.Content is calculated with external standard method.Content is the 90.0-110.0% of labelled amount.
Dissolution determination method：The same assay of chromatographic condition.Leaching condition：Basket method 100rpm, dissolution medium 0.4%
DDAO solution, dissolution medium volume 500ml, 37 ± 0.5 DEG C of medium temperature.Dissolution limit：20min is molten
Go out more than 80%.
Relevant substance-measuring chromatographic condition：Chromatographic column：Octadecyl silane post (250mm × 4.6mm, 5 μm), flowing
Phase A：Water-acetonitrile (85:15), Mobile phase B：Acetonitrile, according to the form below carry out gradient elution.Detection wavelength：252nm, flow velocity：1ml/
Min, sample size：100μl.
Table 1 is about substance gradients type of elution
Impurity content is calculated with area normalization method.Relevant material control limit：List is miscellaneous to be not more than 1.0%, always miscellaneous to be not more than
2.0%.
Specific long-time stability investigate result and see the table below 2-4.
The long-term stable experiment assay result (%) of table 2
The long-term stable experiment dissolution determination result (%) of table 3
The relevant substance-measuring result (%) of the long-term stable experiment of table 4
It can be seen from table 2 and 3,1-6 of the embodiment of the present invention preparation steady quality, content and dissolution rate in storage process
Do not changed in storage process.In storage process, there is the trend slowly reduced in dissolution rate for commercial preparation.Illustrate real
Having good stability for the preparation of a 1-6 is applied, the stabilization of the embodiment of the present invention compared with the paricalcitol preparation of the sale of market
Property is more preferable.
It can be seen from table 4,1-6 of the embodiment of the present invention single miscellaneous and total miscellaneous content of maximum is below commercially available paricalcitol
Preparation, illustrating 1-6 of embodiment of the present invention paricalcitol liquid hard capsule has good stability.
Experimental example 2
3 beasle dogs (being male) are administered orally, they are fed with the embodiment of the present invention 1, commercially available pa respectively
Vertical ossified alcohol soft capasule (specification：1 μ g), dosage is 0.5 μ g/Kg (in terms of paricalcitol), the interval time being administered every time
For 7 days.After giving medicine, blood sample is gathered under different time, and carries out paricalcitol maximum haemoconcentration (Cmax) and life
The calculating of thing availability (AUC0 → 48).Acquisition time is 0h, 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h, 24h,
32h、48h.Table 5 below provides and 3 beasle dogs is given with the embodiment of the present invention 3, flat obtained by commercially available paricalcitol soft capsule
Result.As shown in Table 5, the paricalcitol maximum haemoconcentration and biological utilisation of paricalcitol liquid hard capsule of the present invention
Spend, two kind preparation beasle dog in bioequivalences suitable with commercially available paricalcitol soft capsule.
The experimental result of table 5
By the way that the paricalcitol liquid hard capsule of other embodiments of the invention is tested, identical reality is also obtained
Test result.
In summary, it is 1-6 of the embodiment of the present invention is provided the logical collocation antioxidant of paricalcitol liquid hard capsule, rudimentary
Alcohol and oleaginous base, avoid substantial amounts of auxiliary in order to improve medicine stability in itself and dissolubility addition in the prior art
The defects of material, while without additionally adding other solubilizing auxiliary materials, the paricalcitol liquid hard capsule stability is high, effectively
The content of composition is guaranteed, and the phenomenon for not having aging and content decline in storage process occurs.It is convenient for carrying, the side of taking
Just.The preparation process is easy to operate, and technological parameter is easily-controllable, and production process is green, virtually also reduces production cost,
And reduce manpower and materials cost supporting in production process.
Embodiments described above is part of the embodiment of the present invention, rather than whole embodiments.The reality of the present invention
The detailed description for applying example is not intended to limit the scope of claimed invention, but is merely representative of the selected implementation of the present invention
Example.Based on the embodiment in the present invention, what those of ordinary skill in the art were obtained under the premise of creative work is not made
Every other embodiment, belongs to the scope of protection of the invention.
Claims (10)
1. a kind of paricalcitol liquid hard capsule, it is characterised in that it mainly uses the filling paricalcitol of hard capsule case
Pharmaceutical composition, in parts by weight, the paricalcitol pharmaceutical composition is mainly by 0.25-4 part paricalcitols, 720-
1500 parts of lower alcohol solvents, 50000-290000 parts oleaginous base and 8-20 part antioxidant are made.
2. paricalcitol liquid hard capsule according to claim 1, it is characterised in that the paricalcitol medicine
Composition is mainly by 1-3 parts paricalcitol, 800-1200 parts lower alcohol solvent, 100000-250000 parts institute
State oleaginous base and 10-18 parts antioxidant is made, it is preferable that the paricalcitol pharmaceutical composition is mainly by 2-
2.5 parts of paricalcitols, 900-1000 parts lower alcohol solvent, 150000-200000 parts oleaginous base and 12-
15 parts of antioxidant are made.
3. paricalcitol liquid hard capsule according to claim 1, it is characterised in that the lower alcohol solvent is one
First alcohol, it is preferable that the lower alcohol solvent is the one or more of absolute ethyl alcohol, propyl alcohol or butanol.
4. paricalcitol liquid hard capsule according to claim 1, it is characterised in that during the oleaginous base includes
Chain fatty acid triglycerides, vegetable oil or isopropyl ester type compound, it is preferable that the vegetable oil be coconut oil, castor oil or
One kind in person's soybean oil, the isopropyl ester type compound is isopropyl myristate or isopropyl palmitate, it is further preferred that institute
It is MCT Oil or coconut oil to state oleaginous base.
5. paricalcitol liquid hard capsule according to claim 1, it is characterised in that the antioxidant is dibutyl
Hydroxy-methylbenzene or butylated hydroxy anisole.
6. paricalcitol liquid hard capsule according to claim 1, it is characterised in that the hard capsule case is HPMC
Capsules or gelatin hollow capsule.
7. the preparation method of the paricalcitol liquid hard capsule described in a kind of claim 1, it is characterised in that with parts by weight
Meter, by 0.25-4 parts paricalcitol, 8-20 parts antioxidant and 720-1500 parts lower alcohol solvent mix after again with 50000-
It is filling in hard capsule case after 290000 parts of oleaginous base mixing.
8. preparation method according to claim 7, it is characterised in that the paricalcitol, the antioxidant, described
The mixture of lower alcohol solvent and the oleaginous base is filling to utilize coating material to the hard shell capsules after the hard capsule case
Shell is encapsulated.
9. preparation method according to claim 7, it is characterised in that the paricalcitol, the antioxidant, described
Lower alcohol solvent and oleaginous base mixing are by the paricalcitol, the antioxidant at temperature below 25 DEG C
Mixed with the mixture of the lower alcohol solvent with the oleaginous base.
10. preparation method according to claim 7, it is characterised in that by the paricalcitol, the antioxidant,
The mixture of the lower alcohol solvent and the oleaginous base is filling to the mixture take out very before the hard capsule case
Manage in vacancy.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711062041.3A CN107875134A (en) | 2017-11-02 | 2017-11-02 | paricalcitol liquid hard capsule and preparation method thereof |
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| CN201711062041.3A CN107875134A (en) | 2017-11-02 | 2017-11-02 | paricalcitol liquid hard capsule and preparation method thereof |
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| CN107875134A true CN107875134A (en) | 2018-04-06 |
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| CN201711062041.3A Pending CN107875134A (en) | 2017-11-02 | 2017-11-02 | paricalcitol liquid hard capsule and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110917169A (en) * | 2019-12-11 | 2020-03-27 | 正大制药（青岛）有限公司 | Parlcidol capsule and preparation method thereof |
| CN110917163A (en) * | 2019-12-11 | 2020-03-27 | 正大制药（青岛）有限公司 | Solid oral paricalcitol preparation |
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| CN103110606A (en) * | 2013-02-19 | 2013-05-22 | 青岛正大海尔制药有限公司 | Alfacalcidol capsules and preparation method thereof |
| CN106474086A (en) * | 2015-09-01 | 2017-03-08 | 成都国弘医药有限公司 | A kind of pharmaceutical composition containing paricalcitol 19-Nor-1,25-dihydroxyvitamin D2 |
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| CN103110606A (en) * | 2013-02-19 | 2013-05-22 | 青岛正大海尔制药有限公司 | Alfacalcidol capsules and preparation method thereof |
| CN106474086A (en) * | 2015-09-01 | 2017-03-08 | 成都国弘医药有限公司 | A kind of pharmaceutical composition containing paricalcitol 19-Nor-1,25-dihydroxyvitamin D2 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110917169A (en) * | 2019-12-11 | 2020-03-27 | 正大制药（青岛）有限公司 | Parlcidol capsule and preparation method thereof |
| CN110917163A (en) * | 2019-12-11 | 2020-03-27 | 正大制药（青岛）有限公司 | Solid oral paricalcitol preparation |
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