CN111686091A - Novel paricalcitol soft capsule and preparation method thereof - Google Patents
Novel paricalcitol soft capsule and preparation method thereof Download PDFInfo
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- CN111686091A CN111686091A CN202010609696.3A CN202010609696A CN111686091A CN 111686091 A CN111686091 A CN 111686091A CN 202010609696 A CN202010609696 A CN 202010609696A CN 111686091 A CN111686091 A CN 111686091A
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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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
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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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/20—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of PTH
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- General Health & Medical Sciences (AREA)
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- Orthopedic Medicine & Surgery (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a novel paricalcitol soft capsule and a preparation method thereof, and particularly relates to the technical field of pharmaceutical preparations, wherein the soft capsule comprises a soft capsule filling liquid and a soft capsule shell, wherein the filling liquid consists of paricalcitol, refined vegetable oil, a buffering agent and a flavoring agent; the capsule shell comprises gelatin, thickener, correctant, water, and opacifier. The prepared paricalcitol soft capsule filling liquid has stable quality, can be taken by chewing, can not absorb water to soften the capsule shell, is used for treating secondary hyperparathyroidism and the like of chronic renal failure patients receiving hemodialysis, has the advantages of shortest disintegration time, quick response and high bioavailability, and thus, the paricalcitol soft capsule is obviously superior to the existing products.
Description
Technical Field
The invention relates to the technical field of medicinal preparations, in particular to a novel paricalcitol soft capsule for treating osteoporosis and a preparation method thereof.
Background
Paricalcitol is a synthetic bioactive vitamin D analog with the formula C27H44O3It is a vitamin D analogue developed by Yapei corporation, which exerts corresponding physiological effects by binding to Vitamin D Receptor (VDR) like calcitriol, and is used for treating Secondary Hyperparathyroidism (SHPT) in chronic renal failure patients receiving hemodialysis. The medicine can inhibit parathyroid hormone more quickly and durably, has small influence on calcium, phosphorus and calcium-phosphorus deposition, so continuous hypercalcemia is less generated, the curative effect of the medicine in reducing aortic calcification and improving bone is also better than that of calcitriol, and the medicine can reduce the fatality rate, the hospitalization frequency and the hospitalization time of a patient, so that the medicine is an excellent medicine for treating osteoporosis. In 1998, an injection preparation of paricalcitol was marketed in the U.S. for the prevention and treatment of SHPT, which was effective in the prevention and treatment of SHPT in patients with chronic kidney diseases in stages iii and iv before dialysis and transplantation surgeries.
The paricalcitol is insoluble in water, soluble in organic solvents, very unstable in chemical properties and sensitive to oxygen. At present, the paricalcitol in the market only has two dosage forms, namely a soft capsule and an injection, the dosage forms are single, and the choice of patients is less. The injection is inconvenient to administer and limited in use; the soft capsule has poor stability, and is easy to absorb moisture to influence disintegration and content after long-term storage, thereby influencing bioavailability and curative effect.
Disclosure of Invention
In order to overcome the above defects in the prior art, the embodiments of the present invention provide a novel paricalcitol soft capsule and a preparation method thereof, and the technical problems to be solved by the present invention are: how to reduce the disintegration time and the standing stability of the paricalcitol soft capsule when the soft capsule is taken.
In order to achieve the purpose, the invention provides the following technical scheme: a novel paricalcitol soft capsule is characterized in that: comprises a soft capsule filling liquid and a soft capsule shell, wherein the soft capsule filling liquid comprises, by weight, 0.005-0.05 parts of paricalcitol, 50000 parts of refined vegetable oil 40000-containing sodium chloride, 10-15 parts of a buffering agent, 2-8 parts of a flavoring agent and 10-20 parts of absolute ethyl alcohol; the soft capsule shell consists of 15-40 parts by weight of gelatin, 8-18 parts by weight of thickening agent, 10-20 parts by weight of flavoring agent, 30-50 parts by weight of water and a proper amount of opacifier.
More preferably, the soft capsule filling liquid consists of 0.01 part by weight of paricalcitol, 45000 parts by weight of refined vegetable oil, 12 parts by weight of buffering agent, 5 parts by weight of flavoring agent and 16 parts by weight of absolute ethyl alcohol; the soft capsule shell comprises 35 parts by weight of gelatin, 15 parts by weight of thickening agent, 15 parts by weight of flavoring agent, 40 parts by weight of water and 5 parts by weight of opacifier.
In the specific component formula of the soft capsule filling liquid, the refined vegetable oil is any one or more of soybean oil, peanut oil and sesame oil; the buffer is one or two of citric acid and tartaric acid; the flavoring agent is essence and sweetener.
In a preferred embodiment, the above-mentioned soft capsule filling liquid has a formula of components, the refined vegetable oil is a mixture of soybean oil and peanut oil, and the dosage ratio of the soybean oil to the peanut oil is 1: 1. The buffering agent is citric acid.
A novel paricalcitol soft capsule comprises a soft capsule shell, wherein a thickening agent is one or more of agar, guar gum, low-fat pectin, xanthan gum and locust bean gum; the flavoring agent is essence and sweetener; the opacifier is edible pigment.
Further preferably, in the above formulation of the soft capsule shell, the thickener is agar, guar gum and low-fat pectin, and the ratio of agar: guar gum: the dosage ratio of low-fat pectin is 3:1: 1.
A novel paricalcitol soft capsule is characterized in that: the dosage ratio of the essence and the sweetener in the flavoring agent in the soft capsule filling liquid and the soft capsule shell is 2: 3.
The invention also provides a preparation method of the novel paricalcitol soft capsule, which comprises the following operation steps:
the method comprises the following steps: mixing paricalcitol, buffering agent and correctant, dissolving with anhydrous ethanol, and mixing with refined vegetable oil to obtain soft capsule filling solution;
step two: dissolving the sunscreen agent with a small amount of water; stirring and mixing correctant and water in a gelatin melting tank, heating in water bath, and heating to above 60 deg.C; adding gelatin and thickener, adding opacifier solution, and stirring; heating to 75 ℃, vacuumizing to a vacuum degree of-0.4 bar to-0.8 bar, and vacuumizing for 20 minutes; filtering with 100 mesh net, keeping the temperature at 60 + -5 deg.C, and removing air bubbles to obtain soft capsule shell material;
step three: making into soft capsule by soft capsule machine, and drying.
According to the paricalcitol soft capsule prepared by adopting the raw material formula, the soft capsule skin adopts a formula of matching agar, guar gum and low-fat pectin in proportion, so that the gel hardness is reduced, the elasticity is enhanced, the strength, the thickness and the toughness of the capsule skin are proper, and different amounts of flavoring agents are added into the soft capsule skin and the soft capsule filling liquid, so that the soft capsule disclosed by the invention is good in taste and smell and good in chewiness; the soft capsule shell can not absorb water to soften or deform and be brittle, and the stability is obviously enhanced. The paricalcitol soft capsule is a chewable soft capsule, greatly shortens the disintegration time, and has the advantages of quick response, high bioavailability and obvious advantages compared with similar products.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
The soft capsule is prepared according to the method in the invention.
Example 2
The soft capsule is prepared according to the method in the invention.
Example 3
The soft capsule is prepared according to the method in the invention.
Example 4
The soft capsule is prepared according to the method in the invention.
And (3) selecting 20 persons to evaluate the samples in the embodiment, and evaluating according to the standard that 1-5 points respectively represent very poor, medium, good and good, wherein the average value is listed in table 1.
TABLE 1 sensory evaluation Table
TABLE 2 disintegration time limit
TABLE 3 Long term stability
Therefore, the chewable paricalcitol soft capsule prepared by the formula provided by the invention is good in skin color, aroma and taste, fast in disintegration, good in chewiness and good in long-term stability, and can meet the requirements of consumers.
Finally, it should be noted that: although the present invention has been described in detail with reference to the general description and the specific embodiments, on the basis of the present invention, the above embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (9)
1. A novel paricalcitol soft capsule is characterized in that: comprises a soft capsule filling liquid and a soft capsule shell, wherein the soft capsule filling liquid comprises, by weight, 0.005-0.05 parts of paricalcitol, 50000 parts of refined vegetable oil 40000-containing sodium chloride, 10-15 parts of a buffering agent, 2-8 parts of a flavoring agent and 10-20 parts of absolute ethyl alcohol; the soft capsule shell consists of 15-40 parts by weight of gelatin, 8-18 parts by weight of thickening agent, 10-20 parts by weight of flavoring agent, 30-50 parts by weight of water and a proper amount of opacifier.
2. The novel paricalcitol soft capsule according to claim 1, characterized in that: the soft capsule filling liquid consists of 0.01 part of paricalcitol, 45000 parts of refined vegetable oil, 12 parts of buffering agent, 5 parts of flavoring agent and 16 parts of absolute ethyl alcohol in parts by weight; the soft capsule shell comprises 35 parts by weight of gelatin, 15 parts by weight of thickening agent, 15 parts by weight of flavoring agent, 40 parts by weight of water and 5 parts by weight of opacifier.
3. A novel paricalcitol soft capsule, according to claim 1 or 2, characterized in that: in the component formula of the soft capsule filling liquid, the refined vegetable oil is any one or more of soybean oil, peanut oil and sesame oil; the buffer is one or two of citric acid and tartaric acid; the flavoring agent is essence and sweetener.
4. A novel paricalcitol soft capsule, according to claim 1 or 2, characterized in that: in the component formula of the soft capsule shell, the thickening agent is one or more of agar, guar gum, low-fat pectin, xanthan gum and locust bean gum; the flavoring agent is essence and sweetener; the opacifier is edible pigment.
5. A novel paricalcitol soft capsule, according to claim 3, characterized in that: in the component formula of the soft capsule filling liquid, the refined vegetable oil is a mixture of soybean oil and peanut oil, and the dosage ratio of the soybean oil to the peanut oil is 1: 1.
6. A novel paricalcitol soft capsule, according to claim 3, characterized in that: in the component formula of the soft capsule filling liquid, the buffering agent is citric acid.
7. A novel paricalcitol soft capsule, according to claim 4, characterized in that: in the component formula of the soft capsule shell, the thickening agent is agar, guar gum and low-fat pectin, and the thickening agent is agar: guar gum: the dosage ratio of low-fat pectin is 3:1: 1.
8. A novel paricalcitol soft capsule, according to claims 1-3, characterized in that: the dosage ratio of the essence and the sweetener in the flavoring agent in the soft capsule filling liquid and the soft capsule shell is 2: 3.
9. A preparation method of a novel paricalcitol soft capsule is characterized by comprising the following steps: the method specifically comprises the following operation steps:
the method comprises the following steps: mixing paricalcitol, buffering agent and correctant, dissolving with anhydrous ethanol, and mixing with refined vegetable oil to obtain soft capsule filling solution;
step two: dissolving the sunscreen agent with a small amount of water; stirring and mixing correctant and water in a gelatin melting tank, heating in water bath, and heating to above 60 deg.C; adding gelatin and thickener, adding opacifier solution, and stirring; heating to 75 ℃, vacuumizing to a vacuum degree of-0.4 bar to-0.8 bar, and vacuumizing for 20 minutes; filtering with 100 mesh net, keeping the temperature at 60 + -5 deg.C, and removing air bubbles to obtain soft capsule shell material;
step three: making into soft capsule by soft capsule machine, and drying.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010609696.3A CN111686091A (en) | 2020-06-30 | 2020-06-30 | Novel paricalcitol soft capsule and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010609696.3A CN111686091A (en) | 2020-06-30 | 2020-06-30 | Novel paricalcitol soft capsule and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111686091A true CN111686091A (en) | 2020-09-22 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010609696.3A Withdrawn CN111686091A (en) | 2020-06-30 | 2020-06-30 | Novel paricalcitol soft capsule and preparation method thereof |
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| Country | Link |
|---|---|
| CN (1) | CN111686091A (en) |
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2020
- 2020-06-30 CN CN202010609696.3A patent/CN111686091A/en not_active Withdrawn
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Application publication date: 20200922 |
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| WW01 | Invention patent application withdrawn after publication |