CN1596973A - Interferon-ginseng diol saponin slow-releasing tablet - Google Patents
Interferon-ginseng diol saponin slow-releasing tablet Download PDFInfo
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- CN1596973A CN1596973A CN 200410070703 CN200410070703A CN1596973A CN 1596973 A CN1596973 A CN 1596973A CN 200410070703 CN200410070703 CN 200410070703 CN 200410070703 A CN200410070703 A CN 200410070703A CN 1596973 A CN1596973 A CN 1596973A
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Abstract
A slow-releasing tablet for preventing and treating the virus infection of upper respiratory tract, such as viral cold, SARS, tonsillitis, etc is prepared from recombinant human interferon (IFN), panoxadiol saponin and proper dressing.
Description
Invention field
The present invention relates to prescription, production technology and the indication of recombinant human alpha interferon-ginseng diol saponin tablet.
Background of invention
Interferon is to have multiple bioactive polypeptide, according to its structure difference, can be divided into α type, β type, γ type, ω type etc., and it mainly is to act on body cell, makes cell produce various antiviral proteins, suppresses virus breeding, thereby reaches antivirus action.
Ginseng diol saponin is ginsenoside's a composition, and it contains Rb
1, Rb
2, Rb
3, Rc, Rd, Rg
3Etc. multiple Saponin unit.The physiologically active of finding ginseng diol saponin at present mainly contains shock and anti-stress effect; Damaged cell there is protective effect; The energy microcirculation improvement prevents platelet aggregation; Have activation SOD, reduce lipid peroxide, thus the effect of protection cell and subcellular structure.
Clinically, the generation of disease, development have certain rules, SARS is as a kind of newfound infectious disease, it is got clear substantially at the intravital pathogenic course of machine, SARS is a kind of infectious disease that is caused by SARS virus, it causes the pulmonary's pathological change due to a kind of coronavirus that is similar to infected pigs or cattle in human body, because damage location mainly is positioned at terminal bronchiole epithelial cell and alveolar epithelium, have a strong impact on the external respiration function of breathing mucosa, so the clinical course of acute respiratory failures such as carrying out property respiratory distress syndrome (ivrds), hypoglycemia occurs.
The spike albumen of coronavirus is low with the similar viral homology of other genus, the SARS virus albumen of 5 kinds of unknown function of also encoding in addition, new relatively structural protein and Unknown Function albumen constitute a kind of " superantigen (super antigen) ", can cause the superpower immunoreation of local pulmonary tissue.Inflammatory cytokine and chemotactic factor MCP discharge, and cause the damage of pulmonary vascular endothelial cell and alveolar epithelial cells, and substrate is subsided, thereby induce inflammatory cell to assemble, and produce excessive protease, further increase injury of lung.
At present more, but the therapeutic scheme of generally acknowledging is generally antiviral drugs to the ways and means of the sick treatment of SARS, the medicine of human body immunity improving function, anti-inflammatory drug and reducing inflammation to the hormone medicine of body injury.Wherein, the combination of antiviral drugs and hormonal medicaments is comparatively commonly used.At present the problem that exists is hormonal medicaments such as dexamethasone, and the dosage of use is difficult to grasp, as measures for a short time, is not enough to mitigation symptoms, and one is excessive slightly, then can cause serious sequela such as femur head necrosis, causes new slight illness to the patient.
The applicant has studied through great efforts into a kind of antiviral that gets final product, and can bring into play hormone medicine again, alleviates the new formulation of pathological lesion: the IFN-PDS slow releasing tablet.This tablet can have no side effect to human body through sucking or oral performance drug action, and is easy to use effective.
Summary of the invention
One of the object of the invention provides a kind of prescription of new sustained release tablet
One of another purpose of the present invention provides a kind of new sustained release tablet
Another object of the present invention provides the application of this tablet
Other purpose of the present invention is below to embodying in the specific descriptions of the present invention.
Description of drawings
Accompanying drawing 1 is the sketch map of preparation IFN-PDS slow releasing tablet of the present invention.
IFN-PDS tablet of the present invention adopts solid for mulation, can fully contact with the epithelium mucous membrane in the oral cavity, also can fully contact with intestinal mucosa in enteron aisle, but be insoluble in the gastric juice. Medicine causes mucosal epithelium cell Passive intake by contacting with mucous membrane, the performance drug effect.
According to the present invention, a kind of solid for mulation of IFN-PDS tablet contains recombinant human interferon-alpha, and content is 200-1 * 106IU/ml, the mucous membrane sorbefacient, concentration is 1-10% (W/W), protective agent, concentration is 8-15% (W/W), sustained release agent, concentration is 20-30% (W/W), buffer solution, pH value 6.5-8.5.
According to the present invention, the concentration of mucous membrane sorbefacient is preferably 3-8% (W/W), and protectant concentration is preferably 9-13%, sustained release agent, excellent making into 21.5-24% (W/W). Recombinant human interferon-alpha can be interferon-' alpha ' 2a, interferon alpha 2 b, interferon-' alpha ' 2c or Interferon α1 b, and preferred interferon-' alpha ' is interferon alpha 2 b.
According to the present invention, the mucous membrane sorbefacient is Tween-80, and final concentration: 1-10% (W/W) is preferably 3-8% (W/W); Buffer solution is 0.85% physiological saline; Protective agent is human serum albumin, and final concentration is 8-15%, is preferably 9-13%W/W).
IFN-PDS sustained release tablets of the present invention contains recombinant human interferon-alpha, and content is 2 * 102-
10
6IU/ml, ginseng diol saponin, content are the 0.04-0.1g/ sheet; The mucous membrane sorbefacient: Tween-80, final concentration: 1-10% (W/W) is preferably 3-8% (W/W), and buffer solution is 0.85% physiological saline; Protective agent is human serum albumin, and final concentration is 8-15% (W/W), is preferably 9-13% (W/W); Buffer polyvinyl alcohol 20-30% (W/W) is preferably 21.5-24% (W/W).
IFN-PDS slow releasing tablet of the present invention, by with IFN and PDS and an amount of protective agent, the mucosa absorption enhancer, slow releasing agent mixes and makes, and a kind of scheme of its preparation technology can be referring to accompanying drawing 1.Be used for tablet packaging material of the present invention, be nontoxic, non-stimulated that state approval uses, stable in properties and principal agent and dressing do not play the material manufacture of physical and chemical effect.
For example, the finished product of slow releasing tablet of the present invention can be:
Specification: the 0.25mg/ sheet (contains recombinant human interferon-alpha 2 * 10
2-10
6IU/ml, ginseng diol saponin 0.04-0.1mg).
Storage: 2-8 ℃ of dark cold place.
Packing: non-toxic plastic bubble-cap.
Effect duration: 18 months.
IFN-PDS tablet of the present invention can enhancing human body immunity power, and prevention and sick and other upper respiratory tract infection disease of treatment SARS are as viral influenza.
IFN-PDS tablet formulation of the present invention can be used for preparing tablet of the present invention, and tablet can be used for prevention and treatment respiratory viral infection disease.
The specific embodiment
Embodiment 1
Get general medical dressing starch 40g, add polyvinyl alcohol 25g successively, tween 80 6g, albumin 10g, ginseng diol saponin 20g, stirring and evenly mixing adds interferon 1.6 * 10 again
5The IU/5ml remainder is granulated tabletting after adding 0.85% normal saline mixing.
Embodiment 2
Get general medical dressing starch 40g, add successively and get general medical dressing starch 40g, add polyvinyl alcohol 25g successively, tween 80 6g, albumin 10g, ginseng diol saponin 20g, stirring and evenly mixing adds interferon 1.6 * 10 again
6The IU/5ml remainder is granulated tabletting after adding 0.85% normal saline mixing.
Embodiment 3
Get general medical dressing starch 40g, add successively and get general medical dressing starch 40g, add polyvinyl alcohol 25g successively, tween 80 6g, albumin 10g, ginseng diol saponin 20g, stirring and evenly mixing adds interferon 1.6 * 10 again
7The IU/5ml remainder is granulated tabletting after adding 0.85% normal saline mixing.
One, IFN-PDS slow releasing tablet stability test of the present invention
Material and method
(1) material: IFN-PDS slow releasing tablet of the present invention, be three batches of goods that produce continuously, lot number is 20,040,601 20,040,602 20040603, preserves in 4 ℃ of refrigerators before the test.
(2) method: with above-mentioned three batch samples, preserve separately is placed to reach at that time and is placed the back different time and sampled respectively and carry out the IFN determination of activity, limit test of microbe, outward appearance and tablet weight variation inspection under 4-8 ℃, 20-25 ℃ and 37 ℃ of conditions in batches.
1.IFN biological activity determination: adopt Wish cell-VSV detection system, micro-cytopathic-effect inhibition assay is measured IFN biological activity unit, is just imitating with the interferon standard substance that Nat'l Pharmaceutical ﹠ Biological Products Control Institute takes place frequently.
2.PDS content inspection: adopt the thin layer chromatography scanning method to check.
3. limit test of microbe: undertaken by two version requirements in 2000 of the Pharmacopoeia of the People's Republic of China
4. visual examination: undertaken by " pharmaceutics " method.
5. tablet weight variation: undertaken by two version requirements in 2000 of the Pharmacopoeia of the People's Republic of China.
The result
1. under condition of different temperatures, three batches of IFN Determination of biological activity of recombinant human interferon alpha 2 b tablet of preserving different time see Table 1
Table 1 IFN-PDS slow releasing tablet stability of the present invention measurement result
| Storage temperature (℃) | Lot number | Sampling minute (day) and result (1 * 10 5The IU/ sheet) | ||||
| ??0 | ??1 | ??4 | ??8 | ??12 | ||
| ??4-8 | ?20040601 ?20040602 ?20040603 | ??6.55 ??5.69 ??5.57 | ??6.55 ??5.57 ??5.57 | ??6.40 ??5.57 ??5.50 | ??6.55 ??5.82 ??5.69 | ??6.55 ??5.69 ??5.64 |
| ??20-25 | ?20040601 ?20040602 ?20040603 | ??6.55 ??5.69 ??5.57 | ??6.80 ??5.82 ??5.69 | ??6.50 ??5.57 ??5.50 | ??- ??- ??- | ??- ??- ??- |
| ??37 | ?20040601 ?20040602 ?20040603 | ??6.55 ??5.69 ??5.57 | ??6.80 ??5.57 ??5.82 | ??- ??- ??- | ??- ??- ??- | ??- ??- ??- |
By table 1 as seen: the recombinant human interferon alpha 2 b tablet 4-8 ℃ of condition place at that time with place 12 months after IFN biological activity basically identical, do not fall as follows; Biological activity after placing 4 months under the 20-25 ℃ of condition does not fall as follows; Placing 1 month biological activity under 37 ℃ of conditions does not fall as follows.Basically identical as a result between above-mentioned three batches illustrates that said preparation IFN biological activity is very stable, can preserve more than 12 months under 4-8 ℃ of condition.
2.PDS content inspection: get pure PDS and be contrast, check PDS content in the tablet, getting 10 tablets of IFN-PDS tablets is dissolved in the 10ml water, launch to carry out chromatography with silica gel plate, the plate that chromatography is good develops the color, scanning, scanning result shows, the theoretical numerical value basically identical of the content of ginseng diol saponin and calculating in the tablet.
3. biological limit test: undertaken by two version requirements in 2000 of the Pharmacopoeia of the People's Republic of China, the result shows, contained total number of bacteria in the tablet, and coliform count, the mycete number average meets the requirements.
4. difference test: appoint and get 20 tablets weight of weighing respectively, calculate its average, X=0.24 ± 0.015mg/ sheet meets the pharmacopeia requirement.
5. see and check: get 50 tablets and check that under light the surface finds no pit, foreign body, stain, outward appearance is qualified.
The above results shows that the IFN-PDS tablet technical recipe of production is reasonable, convenient for production, and steady quality is for goods large-scale production in the future and transportation preservation provide reliable scientific basis.
Two. IFN-PDS slow releasing tablet abnormal toxicity test of the present invention
(1) material
1, the recombinant human interferon-alpha of the present invention's use, tiring is 1 * 10
6IU/ml; Ginseng diol saponin, dosage be 40mg/ only, 80mg/ only; Recombinant human interferon-alpha-ginseng diol saponin mixture, dosage are interferon 10
6IU+ ginseng diol saponin 40mg/ only.
2, experimental animal: Cavia porcellus: by Changchun Biological Products Institute's supply body weight is 250-300g.White mice: the KM kind, by Changchun Biological Products Institute's supply, body weight 18-20g.
(2) test method:
2 Cavia porcelluss of every group of dosage, 5 white mice, lumbar injection medicine to be checked is weighed in before the injection, and injection back was observed 7 days, and animal does not occur unusually, and body weight does not descend, and it is qualified to be judged to drug safety.
(3) result
Requirement according to " Chinese biological goods rules " 2000 editions relevant abnormal toxicity tests is tested, and the results are shown in Table 2
Table 2 IFN, PDS and IFN-PDS mixture are to the abnormal toxicity test result of experimental animal
Medicine divides before treated animal (only) administration the differential thing state of flat body weight after the flat administration
Equal weight counterpoise amount (g)
(g)??????(g)
IFN10
6IU mice 18.2 24.1+5.9 is good
Cavia porcellus 260 328+68 is good
PDS80mg white mice 19.0 26.0+7.0 is good
Cavia porcellus 269 336+67 is good
IFN+PDS white mice 18.1 24.0+5.9 is good
Cavia porcellus 255 325+70 is good
By table 2 result as seen, after two kinds of experimental animals finished in the observation period, body weight gain is more obvious, and the high person of PDS dosage is all fast than the low person's body weight gain of dosage, illustrate that PDS and IFN mixture are to the no abnormal toxicity of experimental animal, do not see that after separating plane each internal organs has any change in injection site and the body yet, illustrate that respectively organizing medicine is safe to animal.Above-mentioned test drug dose is 20,000 times that drug dose is used in experiment.
Three, IFN-PDS slow releasing tablet antiviral effect of the present invention
(1) material
1, IFN-PDS slow releasing tablet of the present invention
2, influenza virulent strain: be first 1 type, LD
50=5.0 are provided by Ins of Virology, Beijing
3, experimental animal: 20 every group of KM mice body weight 13-15g
(2) test method:
Choose healthy mice, 20 every group, male and female half and half in test administration the previous day, are attacked with the strong poison of influenza then, observe the back animal dead rate of attacking, to determine the protective effect of medicine to animal.
(3) result
Behind the strong poison of zoogenetic infection influenza, protective rate sees Table 3
The effect that table 3 IFN-PDS mixture various dose resisiting influenza virus infects
| The dosage group | Number of animals (only) | Death toll | The survival number | Protective rate |
| ???4×10 3IU+10mg ???4×10 3IU+20mg ???4×10 4The IU+10mg ribavirin is attacked contrast | ??20 ??20 ??20 ??20 ??20 | ????4 ????2 ????2 ????2 ????15 | ????16 ????18 ????18 ????18 ????5 | ????80 ????90 ????90 ????90 ????25 |
After visible IFN of The above results and PDS share, very good to the animal protection effect, with existing market antiviral specific drug ribavirin therapeutic equivalence commonly used; (do not take medicine apparently higher than matched group; challenge virus) protection illustrates that antiviral effect of the present invention is sure, effectively.
Claims (7)
1, the prescription of recombinant human interferon alpha 2-ginseng diol saponin (IFN-PDS) mixture comprises recombinant human interferon-alpha, content: 200-1 * 10
6IU/ml; Ginseng diol saponin content: 0.04-0.1g/ sheet
The mucosa absorption enhancer: concentration is 5-20%
Protective agent: concentration is 8-15%
Slow releasing agent: concentration is 1-10%
Buffer: PH is 6.5-8.5
2, the prescription of claim 1, wherein the mucosa absorption enhancer is a taurine
3, the prescription of claim 1, wherein protective agent is the human albumin
4, the prescription of claim 1, wherein slow releasing agent is a polyvinyl alcohol
5, buffer: be phosphate buffer normal saline
6, the application of the prescription of claim 1-5 in the tablet formulation of preparation prevention and treatment respiratory viral infection disease
7, the application of claim 6, wherein respiratory viral infection disease is a viral influenza, SARS virus infects, tonsillitis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410070703 CN1596973A (en) | 2004-07-21 | 2004-07-21 | Interferon-ginseng diol saponin slow-releasing tablet |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410070703 CN1596973A (en) | 2004-07-21 | 2004-07-21 | Interferon-ginseng diol saponin slow-releasing tablet |
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| Publication Number | Publication Date |
|---|---|
| CN1596973A true CN1596973A (en) | 2005-03-23 |
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| CN 200410070703 Pending CN1596973A (en) | 2004-07-21 | 2004-07-21 | Interferon-ginseng diol saponin slow-releasing tablet |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103446207A (en) * | 2013-01-11 | 2013-12-18 | 上海禾易生物技术发展有限公司 | Preparation method and application of reagent for activating human immune cells |
-
2004
- 2004-07-21 CN CN 200410070703 patent/CN1596973A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103446207A (en) * | 2013-01-11 | 2013-12-18 | 上海禾易生物技术发展有限公司 | Preparation method and application of reagent for activating human immune cells |
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