CN1887346A - Recombinant human interferon-alpha-thymulin medicine composition and its applied prepn form - Google Patents
Recombinant human interferon-alpha-thymulin medicine composition and its applied prepn form Download PDFInfo
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- CN1887346A CN1887346A CN 200510081539 CN200510081539A CN1887346A CN 1887346 A CN1887346 A CN 1887346A CN 200510081539 CN200510081539 CN 200510081539 CN 200510081539 A CN200510081539 A CN 200510081539A CN 1887346 A CN1887346 A CN 1887346A
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Abstract
The present invention discloses medicine composition comprising recombinant human interferon-alpha and thymulin in certain ratio. The medicine composition has recombinant human interferon-alpha and thymulin as the main components and excipient. It has the bioactivity of recombinant human interferon-alpha and the immune stimulating activity of thymulin, and may be used in preventing and treating viral diseases, enhancing body's immunity and anti-inflammatory action and lowering the toxic side effect of cell factor. The effective component of small molecular polypeptide becomes the cell factor protecting agent to raise the biostability. The present invention also relates to the specific preparation forms, such as freeze dried powder for injection, spary, suppository, etc.
Description
Technical field
The present invention relates to drug world, more specifically, the present invention relates to the medicine that recombinant human interferon-alpha, thymus active polypeptide combine by a certain percentage, this medicine can be used for preventing and treating the infringement of viral disease, special antagonism viral infection has unique effect, but and enhancing human body immunity power.
Background technology
Interferon at first is found in nineteen fifty-seven, Isaaca and Lindenmann are referred to as to induce the cellular products to homology or allos viral infection generation resistance, through research for many years, people recognize to disturb and have many biological activitys, wherein antiviral activity is that domestic and international expert generally acknowledges, has effects such as stronger inhibition virus breeding and immunomodulating.People such as Capon D.J. report, interferon can improve immunocompetence, thereby plays antiviral prevention and therapeutic effect (Capon D.J, Shepard, H.M.andGoeddel D.V., Mol.Cell.Biol.5 (4), 768-779,1985).
At present, interferon has been approved for multiple prevention and treatment of diseases such as viral infection.
The thymus active polypeptide is a kind of active polypeptide para-immunity hormone that extracts from the calf thymus tissue.The thymus active polypeptide can be participated in the body cell immunoreation directly, and impelling lymphocyte transformation is the T-lymphoblast, keeps the lymphocytic normal level of T-in the human body, thereby makes body keep the ability of defend against computer virus infringement, also has antiinflammatory action simultaneously.
Although interferon and thymus active polypeptide are used for prevention and treatment viral disease and immunomodulating clinically, but seek to have the medicine of better antiviral and immunomodulating biological activity and higher biological stability, be the target of the long-term and unremitting effort of people always.
Summary of the invention
The inventor is unexpected under study for action to be found, the pharmaceutical composition that contains recombinant human interferon-alpha and thymus active polypeptide aspect prevention and treatment viral disease and immunomodulating, has synergism, and the raising of the biological stability of pharmaceutical composition, can be 2-8 ℃ of preservation.
Therefore, one object of the present invention just provides a kind of pharmaceutical composition, contains recombinant human interferon-alpha and thymus active polypeptide.
Another object of the present invention is the application for preparing in the pharmaceutical composition of the present invention that is combined in of recombinant human interferon-alpha and thymus active polypeptide.
Other purposes of the present invention embody in to specific descriptions of the present invention in this description.
According to the present invention, a kind of pharmaceutical composition contains recombinant human interferon-alpha and thymus active polypeptide, and pharmaceutically acceptable adjuvant and/or excipient.
In the pharmaceutical composition of the present invention, recombinant human interferon-alpha: 50IU-200 ten thousand every milliliter of IU or every preparation unit; Thymus bioactive peptide: every milliliter of 5-100mg or every preparation unit, every milliliter of preferred 5-20mg or every preparation unit.Said preparation unit is meant, for example,, piece, sheet, grain or the like.
According to the present invention, recombinant human interferon-alpha can be interferon-ALPHA 2a, interferon alpha 2 b, and interferon-ALPHA 1b, preferred recombinant human interferon-alpha is an interferon alpha 2 b.
In pharmaceutical composition of the present invention, the thymus active polypeptide molecular weight of use is lower than 10,000 dalton, and its safety is very high.
Pharmaceutical composition of the present invention can be made multiple dosage form, for example, and injection, spray, suppository, tablet, capsule, nasal drop.The example of adjuvant and/or excipient comprises: mannitol, trehalose, microcrystalline Cellulose, dried starch, dextrin, carboxymethyl starch sodium, polyacrylic resin, ethanol, Tween-80, gelatin, glycerol, water, soybean lecithin, propylene glycol, Borneolum Syntheticum, phenylacetic acid, starch slurry, magnesium stearate etc.Adjuvant also comprises wetting agent, antiseptic, promoter.
Pharmaceutical composition of the present invention has good biological stability, thereby end user's blood albumin protective agent is not kept the biological stability of pharmaceutical composition, thereby has avoided polluting because of the potential cause of disease that end user's blood albumin protective agent produces.
In the spray of pharmaceutical composition of the present invention, recombinant human interferon-alpha: 50IU-50 ten thousand IU/mL; Thymus bioactive peptide: 5-50mg/mL, preferred 5-20mg/mL.
In the freeze dried injection of pharmaceutical composition of the present invention, recombinant human interferon-alpha: 1,000,000 IU-200, ten thousand IU/mL; Thymus bioactive peptide: 5-100mg/mL, preferred 5-20mg/mL.
In the suppository of pharmaceutical composition of the present invention, recombinant human interferon-alpha: ten thousand IU/ pieces of 10,000 IU-100; Thymus bioactive peptide: 5-50mg/ piece, preferred 5-20mg/ piece.
In the tablet of pharmaceutical composition of the present invention, recombinant human interferon-alpha: 50IU-50 ten thousand IU/ sheets; Thymus bioactive peptide: 5-50mg/ sheet, preferred 5-20mg/ sheet.
In the capsule of pharmaceutical composition of the present invention, recombinant human interferon-alpha: 50IU-50 ten thousand IU/ grains; Thymus bioactive peptide: 5-50mg/ grain, preferred 5-20mg/ grain.
In the nasal drop of pharmaceutical composition of the present invention, recombinant human interferon-alpha: 50IU-50 ten thousand IU/ grains; Thymus bioactive peptide: 5-50mg/mL, preferred 5-20mg/mL.
According to the present invention, pharmaceutical composition of the present invention also can contain adjuvant, as wetting agent, antiseptic, promoter, buffer or the like.
Each composition in the pharmaceutical composition of the present invention as recombinant human interferon-alpha, thymus bioactive peptide or the like, all can be buied from the market.
One, the synergism of pharmaceutical composition of the present invention
Get mice and divide three groups at random: composition of medicine group of the present invention, recombinant human interferon alpha 2 b group and normal saline matched group, use various dose respectively, adopt collunarium and two kinds of route of administration of injection, and used the influenza virus of half lethal dose that mice is attacked in forward and backward 24 hours in administration respectively.Observe and record mice existence situation.The results are shown in Table 1-1,1-2,1-3.In table 1-1,1-2,1-3, the thymosin content of pharmaceutical composition of the present invention is 5mg/mL, and recombinant human interferon alpha 2 b content is respectively 2,000,000 IU/mL, 500,000 IU/mL, 50IU/mL.
The synergistic result (containing α 2b,200 ten thousand IU) of table 1-1 pharmaceutical composition of the present invention
| Route of administration | Medicine | Content of dispersion (every ml) | Dosage (uL) | Administration time (my god) | Attack time | Number of mice (only) | Survival rate (%) |
| Injection | This composition of medicine | 2,000,000 IU 5mg | 50 | 10 | After the administration | 18 | 72.2 |
| Interferon alpha 2 b | 2,000,000 IU | 50 | 10 | After the administration | 18 | 61.1 | |
| Normal saline | 0.85％ | 50 | 10 | After the administration | 18 | 44.4 | |
| Collunarium | This composition of medicine | 2,000,000 IU 5mg | 30 | 10 | After the administration | 18 | 77.8 |
| Interferon alpha 2 b | 2,000,000 IU | 30 | 10 | After the administration | 18 | 61.1 | |
| Normal saline | 0.85％ | 30 | 10 | After the administration | 18 | 44.4 | |
| Injection | This composition of medicine | 2,000,000 IU 5mg | 50 | 3 | Before the administration | 18 | 61.1 |
| Interferon alpha 2 b | 2,000,000 IU | 50 | 3 | Before the administration | 18 | 50.0 | |
| Normal saline | 0.85％ | 50 | 3 | Before the administration | 18 | 50.0 | |
| Collunarium | This composition of medicine | 2,000,000 IU 5mg | 30 | 3 | Before the administration | 18 | 66.7 |
| Interferon alpha 2 b | 2,000,000 IU | 30 | 3 | Before the administration | 18 | 50.0 | |
| Normal saline | 0.85％ | 30 | 3 | Before the administration | 18 | 50.0 |
The synergistic result (containing α 2,b50 ten thousand IU) of table 1-2 pharmaceutical composition of the present invention
| Route of administration | Medicine | Content of dispersion (every ml) | Dosage (uL) | Administration time (my god) | Attack time | Number of mice (only) | Survival rate (%) |
| Injection | This composition of medicine | 500,000 IU 5mg | 50 | 10 | After the administration | 18 | 61.1 |
| Interferon alpha 2 b | 500,000 IU | 50 | 10 | After the administration | 18 | 55.6 | |
| Normal saline | 0.85％ | 50 | 10 | After the administration | 18 | 50.0 | |
| Collunarium | This composition of medicine | 500,000 IU 5mg | 30 | 10 | After the administration | 18 | 66.7 |
| Interferon alpha 2 b | 500,000 IU | 30 | 10 | After the administration | 18 | 55.6 | |
| Normal saline | 0.85％ | 30 | 10 | After the administration | 18 | 44.4 | |
| Injection | This composition of medicine | 500,000 IU 5mg | 50 | 3 | Before the administration | 18 | 55.6 |
| Interferon alpha 2 b | 500,000 IU | 50 | 3 | Before the administration | 18 | 50.0 | |
| Normal saline | 0.85％ | 50 | 3 | Before the administration | 18 | 50.0 | |
| Collunarium | This composition of medicine | 500,000 IU 5mg | 30 | 3 | Before the administration | 18 | 61.1 |
| Interferon alpha 2 b | 500,000 IU | 30 | 3 | Before the administration | 18 | 44.4 | |
| Normal saline | 0.85％ | 30 | 3 | Before the administration | 18 | 50.0 |
The synergistic result (containing α 2b50IU) of table 1-3 pharmaceutical composition of the present invention
| Route of administration | Medicine | Content of dispersion (every m1) | Dosage (uL) | Administration time (my god) | Attack time | Number of mice (only) | Survival rate (%) |
| Injection | This composition of medicine | 50IU 5mg | 50 | 10 | After the administration | 18 | 55.6 |
| Interferon alpha 2 b | 50IU | 50 | 10 | After the administration | 18 | 50.0 | |
| Normal saline | 0.85％ | 50 | 10 | After the administration | 18 | 50.0 | |
| Collunarium | This composition of medicine | 50IU 5mg | 30 | 10 | After the administration | 18 | 55.6 |
| Interferon alpha 2 b | 50IU | 30 | 10 | After the administration | 18 | 50.0 | |
| Normal saline | 0.85％ | 30 | 10 | After the administration | 18 | 44.4 | |
| Injection | This composition of medicine | 50IU 5mg | 50 | 3 | Before the administration | 18 | 50.0 |
| Interferon alpha 2 b | 50IU | 50 | 3 | Before the administration | 18 | 50.0 | |
| Normal saline | 0.85％ | 50 | 3 | Before the administration | 18 | 44.4 | |
| Collunarium | This composition of medicine | 50IU 5mg | 30 | 3 | Before the administration | 18 | 55.6 |
| Interferon alpha 2 b | 50IU | 30 | 3 | Before the administration | 18 | 44.4 | |
| Normal saline | 0.85％ | 30 | 3 | Before the administration | 18 | 50.0 |
Repeatedly experimental result is learned processing by statistics, and P＜0.05 shows composition of medicine of the present invention and simple interferon to make the survival rate of mouse anti influenza virus there were significant differences.From table 1-1,1-2,1-3 as seen, injection and collunarium administration, the survival rate that mice is used composition of medicine of the present invention is higher than simple interferon group.Illustrate between interferon and the thymosin synergism is arranged.
Two, the biological stability result of pharmaceutical composition of the present invention
Composition of medicine of the present invention is contained recombinant human interferon alpha 2 b (2,000,000 IU/mL), thymus bioactive peptide (50mg/mL) and simple recombinant human interferon alpha 2 b (2,000,000 IU/mL), deposit accelerated test and the long term test of doing recombinant human interferon alpha 2 b under different temperatures, the result sees Table 2-1 and table 2-2 respectively.
Table 2-1 accelerated test result
| Medicine | Storage temperature (℃) | Resting period (moon) | Appearance luster | Activity change | PH changes | Clarity |
| Interferon (containing α 2b,200 ten thousand IU) | 40 | 1 | No change | No change | No change | No change |
| 40 | 2 | No change | No change | No change | No change | |
| 40 | 3 | No change | Reduce | No change | No change | |
| 40 | 6 | No change | Non-activity | No change | No change | |
| Composition of medicine (containing α 2b,200 ten thousand IU) | 40 | 1 | No change | No change | No change | No change |
| 40 | 2 | No change | No change | No change | No change | |
| 40 | 3 | No change | No change | No change | No change | |
| 40 | 6 | No change | No change | No change | No change |
Table 2-2 long-term test results
| Medicine | Storage temperature (℃) | Resting period (moon) | Appearance luster | Activity change | PH changes | Clarity |
| Interferon (containing α 2b,200 ten thousand IU) | 25 | 3 | No change | No change | No change | No change |
| 25 | 6 | No change | Reduce | No change | No change | |
| 25 | 9 | No change | Reduce | No change | No change | |
| 25 | 12 | No change | Non-activity | No change | No change | |
| 25 | 18 | No change | Non-activity | No change | No change | |
| Composition of medicine (containing α 2b,200 ten thousand IU) | 25 | 3 | No change | No change | No change | No change |
| 25 | 6 | No change | No change | No change | No change | |
| 25 | 9 | No change | No change | No change | No change | |
| 25 | 12 | No change | No change | No change | No change | |
| 25 | 18 | No change | No change | No change | No change |
Pharmaceutical composition of the present invention had both had the biological activity of recombinant human interferon-alpha, the immunostimulatory activity that has simultaneously thymosin again, can be used for prevention and treatment as viral disease, but the immunity and the antiinflammatory action of while enhancing body, reduce the toxic and side effects of cytokine, for example can be used for prevention and treatment influenza, hepatitis A, hepatitis B, upper respiratory tract infection, allergy or the like.In pharmaceutical composition of the present invention, micromolecule polypeptide effectively becomes the cytokine protective agent, makes biological stability improve.
Pharmaceutical composition of the present invention can carry out administration to the significant dosage of patient (effective dose) when treating and/or preventing, also can be as required and the medication combined application of other treatment.
According to the present invention, the combination of recombinant human interferon-alpha and thymus active polypeptide is used to prepare pharmaceutical composition of the present invention.
According to the present invention, pharmaceutical composition of the present invention and various dosage form thereof can prepare with the method for routine.
The specific embodiment
Below in conjunction with specific embodiment, further set forth the present invention.
Embodiment 1: preparation of drug combination of the present invention
Recombinant human interferon alpha 2 b and thymus active polypeptide with biologically active, use 20mM phosphate, it is 7.2 that the buffer of 0.145MnaCl is transferred PH, then recombinant human interferon alpha 2 b and thymus active polypeptide is mixed by usage ratio, aseptic filtration is examined and determine by the requirement of biological product semi-finished product again.
I: thymosin determination of activity in the pharmaceutical composition of the present invention
1. take off the preparation of enzyme acceptor thymus T cell suspension: get fresh pig thymus, get fat and shred, add an amount of Hank ' s liquid and make into cell suspension, filter through 100 mesh sieves, per minute 1500 leaves heart 3-5 minute, abandon or adopt supernatant, adding small amount of H ank ' s liquid is beaten even, and this solution is added with in the centrifuge tube with 1/3 amount of filtrate, leaves the heart 20 minutes with per minute 2000, the thymocyte cell in careful sucking-off intermediate layer, put into another centrifuge tube, add an amount of Hank ' s liquid washing, shake up, leave heart 3-5 minute with per minute 1500, abandon or adopt supernatant, after the washing once, in precipitate, add an amount of Hank ' s liquid, mixing, 30 minutes (once) of 45 ℃ of water bath with thermostatic control insulations every jolting in 5 minutes.Per minute 1500 leaves heart 3-5 minute, abandons or adopts supernatant, uses Hank ' s liquid washing three times (operation is the same), uses dilution of Hank ' s liquid and counting at last, and making ultimate density is among every 1ml 3 * 10
6-5 * 10
6Individual cell.
2. the preparation of sheep erythrocyte suspension: get an amount of Sanguis caprae seu ovis, use Hank ' s liquid give a baby a bath on the third day after its birth time (ditto).Abandon or adopt supernatant, use Hank ' s liquid dilution and counting, make ultimate density be take off enzyme acceptor thymus T concentration of cell suspension 8-10 doubly.
3. the preparation of test sample: get test sample, use Hank ' s liquid to be mixed with the solution that contains 1mg among every 1ml.
4. measure: get 6 of small test tubes, wherein 3 respectively add Hank ' s liquid 0.1ml and oppose and look after, three respectively add need testing solution 0.1ml work mensuration pipe in addition, add in every pipe and take off enzyme acceptor thymus T cell suspension 0.2ml, 37 ℃ of insulations are after 1 hour, add sheep erythrocyte suspension 0.2ml, shake up, left the heart 3 minutes with per minute 500, put into 4 ℃ of refrigerator overnight, take out next day, abandoning supernatant, add one of fixative in every pipe, shake up gently, left standstill 10 minutes, 2 of dyeing liquors of adding also shake up, leave standstill and begin counting after 15 minutes, the bigger cell of pale blue is a lymphocyte in the field of microscope, and all lymphocytic numbers (being no less than 200) on 16 big grids of counting number plate are added up the cell number (in conjunction with the lymphocyte of 3 above sheep red blood cell (SRBC)s) that E rosette wherein forms altogether, try to achieve knot flower percentage rate, average.Be the meansigma methods of test sample pipe or control tube.
II: recombinant human interferon alpha 2 b determination of activity in the pharmaceutical composition of the present invention
Adopt cytopathic effect to suppress to be basic inhibition microdetermination.The dilution inverse that still can protect the half cell to avoid virus attack with the high dilution of every milliliter of recombinant human interferon alpha 2 b inspection product is decided to be recombinant human interferon alpha 2 b unit.Represent with iu, and proofread and correct the result with the national standard product.The concentration of the fresh 24-48 of going down to posterity hour wish cell with about 350,000/ml is added in the 96 hole tissue culturing plates, and every hole 100 μ l put 37 ℃ of 5%CO
2Cultivated 4-6 hour in the incubator.Recombinant human interferon-alpha inspection product are done 4 times of serial dilutions, and every part of inspection product are done 6 dilution factors and (as being 1,000,000 IU/ml, then can be diluted 4
-12-4
-7), each dilution factor adds 2 holes, with the cell mixed in equal amounts in the culture plate, puts 37 ℃ of 5%CO
2Cultivated 18-24 hour in the incubator.To the supernatant that falls in the culture plate, with 100CCID
50The concentration of/ml adds VSV (blister stomatitis virus), and every hole adds 100 μ l, 37 ℃ of 5%CO
2Cultivated about 24 hours in the incubator.Microscopically observation of cell pathological changes, if obvious pathological changes and the death of 75%-100% appear in each porocyte of virus control, and the well-grown still of the cell in the cell matched group shows that then contradistinction system is qualified, the result sets up.
Sample vigor=test sample is measured pipe E rosette percentage rate-control tube E rosette percentage rate
Embodiment 2: the preparation of the freeze dried injection of pharmaceutical composition of the present invention
Get the pharmaceutical composition semi-finished product of the present invention of assay approval; contain recombinant human interferon alpha 2 b 1,000,000 IU/ml, thymus peptide 1 0mg/ml; add 4% trehalose, behind the 4% mannitol protective agent mix homogeneously, with the filter membrane aseptic filtration in 0.22um aperture; sampling is done aseptic and heat source check; be sub-packed in after qualified in the cillin bottle, hundred grades of clean areas carry out, every bottle of 1.1ml; lyophilizing after the packing, finished product are put in dark place preservation between 2-4 ℃.
Embodiment 3: the preparation of the freeze dried injection of pharmaceutical composition of the present invention
Get the pharmaceutical composition semi-finished product of the present invention of assay approval; contain recombinant human interferon alpha 2 b 1,000,000 IU/ml, thymosin 20mg/ml; add 4% trehalose, behind the 4% mannitol protective agent mix homogeneously, with the filter membrane aseptic filtration in 0.22um aperture; sampling is done aseptic and heat source check; be sub-packed in after qualified in the cillin bottle, hundred grades of clean areas carry out, every bottle of 1.1ml; lyophilizing after the packing, finished product are put in dark place preservation between 2-4 ℃.
Embodiment 4: the preparation of the freeze dried injection of pharmaceutical composition of the present invention
Get the pharmaceutical composition semi-finished product of the present invention of assay approval; contain recombinant human interferon alpha 2 b 2,000,000 IU/ml, thymus peptide 1 0mg/ml; add 4% trehalose, behind the 4% mannitol protective agent mix homogeneously, with the filter membrane aseptic filtration in 0.22um aperture; sampling is done aseptic and heat source check; be sub-packed in after qualified in the cillin bottle, hundred grades of clean areas carry out, every bottle of 1.1ml; lyophilizing after the packing, finished product are put in dark place preservation between 2-4 ℃.
Embodiment 5: the preparation of the freeze dried injection of pharmaceutical composition of the present invention
Get the pharmaceutical composition semi-finished product of the present invention of assay approval; contain recombinant human interferon alpha 2 b 2,000,000 IU/ml, thymosin 20mg/ml; add 4% trehalose, behind the 4% mannitol protective agent mix homogeneously, with the filter membrane aseptic filtration in 0.22um aperture; sampling is done aseptic and heat source check; be sub-packed in after qualified in the cillin bottle, hundred grades of clean areas carry out, every bottle of 1.1ml; lyophilizing after the packing, finished product are put in dark place preservation between 2-4 ℃.
Embodiment 6: the preparation of pharmaceutical composition suppository of the present invention
Water: gelatin: the substrate 17.5L of glycerol=1: 2: 5, be incubated in 56 ℃, add pharmaceutical composition stock solution 530ml of the present invention (final concentration contain recombinant human interferon alpha 2 b 250,000 IU/ pieces, thymus peptide 1 0mg/ piece), DMSO 100ml, gentamycin 500ml 100 pieces of the packing that stir.Finished product is put in dark place preservation between 2-4 ℃.
Embodiment 7: the preparation of pharmaceutical composition suppository of the present invention
Water: gelatin: the substrate 17.5L of glycerol=1: 2: 5, be incubated in 56 ℃, add pharmaceutical composition stock solution 530ml of the present invention (final concentration contain recombinant human interferon alpha 2 b 250,000 IU/ pieces, thymosin 20mg/ piece), DMSO 100ml, gentamycin 500ml 100 pieces of the packing that stir.Finished product is put in dark place preservation between 2-4 ℃.
Embodiment 8: the preparation of pharmaceutical composition suppository of the present invention
Water: gelatin: the substrate 17.5L of glycerol=1: 2: 5, be incubated in 56 ℃, add pharmaceutical composition stock solution 530ml of the present invention (final concentration contain recombinant human interferon alpha 2 b 500,000 IU/ pieces, thymus peptide 1 0mg/ piece), DMSO 100ml, gentamycin 500ml 100 pieces of the packing that stir.Finished product is put in dark place preservation between 2-4 ℃.
Embodiment 9: the preparation of pharmaceutical composition suppository of the present invention
Water: gelatin: the substrate 17.5L of glycerol=1: 2: 5, be incubated in 56 ℃, add pharmaceutical composition stock solution 530ml of the present invention (final concentration contain recombinant human interferon alpha 2 b 500,000 IU/ pieces, thymosin 20mg/ piece), DMSO 100ml, gentamycin 500ml 100 pieces of the packing that stir.Finished product is put in dark place preservation between 2-4 ℃.
Embodiment 10: the preparation of medicament composition capsule agent of the present invention
Freeze dried pharmaceutical composition 20 grams (every capsules contains recombinant human interferon alpha 2 b 100IU, thymus peptide 1 0mg/ grain) of the present invention are restrained itself and microcrystalline Cellulose 35, dried starch 100 grams, dextrin 15 grams, carboxymethyl starch sodium 12 gram mixings, it is stand-by to cross 80 mesh sieves; Get polyacrylic resin 4 gram, it is in 90% the alcoholic solution, to be mixed with adhesive that Tween80 0.3ml adds concentration, add in the above-mentioned compound, make soft material, cross 26 mesh sieves and granulate, 37 ℃ of vacuum dryings 24 hours are dressed up 1000 with No. 2 colon soluble gum softgel shells behind the 20 mesh sieve granulate.
Embodiment 11: the preparation of medicament composition capsule agent of the present invention
Freeze dried pharmaceutical composition 20 grams (every capsules contains recombinant human interferon alpha 2 b 100IU, thymosin 20mg/ grain) of the present invention are restrained itself and microcrystalline Cellulose 35, dried starch 100 grams, dextrin 15 grams, carboxymethyl starch sodium 12 gram mixings, it is stand-by to cross 80 mesh sieves; Get polyacrylic resin 4 gram, it is in 90% the alcoholic solution, to be mixed with adhesive that Tween80 0.3ml adds concentration, add in the above-mentioned compound, make soft material, cross 26 mesh sieves and granulate, 37 ℃ of vacuum dryings 24 hours are dressed up 1000 with No. 2 colon soluble gum softgel shells behind the 20 mesh sieve granulate.
Embodiment 12: the preparation of medicament composition capsule agent of the present invention
Freeze dried pharmaceutical composition 20 grams (every capsules contains recombinant human interferon alpha 2 b 200IU, thymus peptide 1 0mg/ grain) of the present invention are restrained itself and microcrystalline Cellulose 35, dried starch 100 grams, dextrin 15 grams, carboxymethyl starch sodium 12 gram mixings, it is stand-by to cross 80 mesh sieves; Get polyacrylic resin 4 gram, it is in 90% the alcoholic solution, to be mixed with adhesive that Tween800.3ml adds concentration, add in the above-mentioned compound, make soft material, cross 26 mesh sieves and granulate, 37 ℃ of vacuum dryings 24 hours are dressed up 1000 with No. 2 colon soluble gum softgel shells behind the 20 mesh sieve granulate.
Embodiment 13: the preparation of medicament composition capsule agent of the present invention
Freeze dried pharmaceutical composition 20 grams (every capsules contains recombinant human interferon alpha 2 b 200IU, thymosin 20mg/ grain) of the present invention are restrained itself and microcrystalline Cellulose 35, dried starch 100 grams, dextrin 15 grams, carboxymethyl starch sodium 12 gram mixings, it is stand-by to cross 80 mesh sieves; Get polyacrylic resin 4 gram, it is in 90% the alcoholic solution, to be mixed with adhesive that Tween800.3ml adds concentration, add in the above-mentioned compound, make soft material, cross 26 mesh sieves and granulate, 37 ℃ of vacuum dryings 24 hours are dressed up 1000 with No. 2 colon soluble gum softgel shells behind the 20 mesh sieve granulate.
Embodiment 14: the preparation of medicinal composition spray of the present invention
Get soybean lecithin 50 grams and add propylene glycol 30ml and be dissolved in the alcoholic acid 8 gram Borneolum Syntheticums of 15ml, slowly be stirred to soybean lecithin and dissolve fully; Pharmaceutical composition of the present invention is dissolved in PH7.2 to be contained in the phosphate buffer of 10mM 60ml of 5 gram phenethanol (final concentration contains recombinant human interferon alpha 2 b 100IU/ml, thymus peptide 1 0mg/ml), slowly join then in the propylene glycol solution of soybean lecithin and stir, divide after the degerming and install to the 5.0ml/ bottle, in the hand micro-sprayer of 10ml/ bottle, the collodion sealing.
Embodiment 15: the preparation of medicinal composition spray of the present invention
Get soybean lecithin 50 grams and add propylene glycol 30ml and be dissolved in the alcoholic acid 8 gram Borneolum Syntheticums of 15ml, slowly be stirred to soybean lecithin and dissolve fully; Pharmaceutical composition of the present invention is dissolved in PH7.2 to be contained in the phosphate buffer of 10mM 60ml of 5 gram phenethanol (final concentration contains recombinant human interferon alpha 2 b 100IU/ml, thymosin 20mg/ml), slowly join then in the propylene glycol solution of soybean lecithin and stir, divide after the degerming and install to the 5.0ml/ bottle, in the hand micro-sprayer of 10ml/ bottle, the collodion sealing.
Embodiment 16: the preparation of medicinal composition spray of the present invention
Get soybean lecithin 50 grams and add propylene glycol 30ml and be dissolved in the alcoholic acid 8 gram Borneolum Syntheticums of 15ml, slowly be stirred to soybean lecithin and dissolve fully; Pharmaceutical composition of the present invention is dissolved in PH7.2 to be contained in the phosphate buffer of 10mM 60ml of 5 gram phenethanol (final concentration contains recombinant human interferon alpha 2 b 200IU/ml, thymus peptide 1 0mg/ml), slowly join then in the propylene glycol solution of soybean lecithin and stir, divide after the degerming and install to the 5.0ml/ bottle, in the hand micro-sprayer of 10ml/ bottle, the collodion sealing.
Embodiment 17: the preparation of medicinal composition spray of the present invention
Get soybean lecithin 50 grams and add propylene glycol 30ml and be dissolved in the alcoholic acid 8 gram Borneolum Syntheticums of 15ml, slowly be stirred to soybean lecithin and dissolve fully; Pharmaceutical composition of the present invention is dissolved in PH7.2 to be contained in the phosphate buffer of 10mM 60ml of 5 gram phenethanol (final concentration contains recombinant human interferon alpha 2 b 200IU/ml, thymosin 20mg/ml), slowly join then in the propylene glycol solution of soybean lecithin and stir, divide after the degerming and install to the 5.0ml/ bottle, in the hand micro-sprayer of 10ml/ bottle, the collodion sealing.
Embodiment 18: the preparation of pharmaceutical composition tablet of the present invention
Freeze dried pharmaceutical composition 20 grams (every contains recombinant human interferon alpha 2 b 100IU, thymus peptide 1 0mg) of the present invention are added starch 300 grams, add 40 gram starch slurries behind the mixing and be mixed and made into soft material, 14 mesh sieves are granulated, 37 ℃ of vacuum dryings 24 hours, add magnesium stearate 2.5 grams and Sodium Hydroxymethyl Stalcs 5 gram mixings behind the 14 mesh sieve granulate, 1000 of tablettings.
Embodiment 19: the preparation of pharmaceutical composition tablet of the present invention
Freeze dried pharmaceutical composition 20 grams (every contains recombinant human interferon alpha 2 b 100IU, thymosin 20mg) of the present invention are added starch 300 grams, add 40 gram starch slurries behind the mixing and be mixed and made into soft material, 14 mesh sieves are granulated, 37 ℃ of vacuum dryings 24 hours, add magnesium stearate 2.5 grams and Sodium Hydroxymethyl Stalcs 5 gram mixings behind the 14 mesh sieve granulate, 1000 of tablettings.
Embodiment 20: the preparation of pharmaceutical composition tablet of the present invention
Freeze dried pharmaceutical composition 20 grams (every contains recombinant human interferon alpha 2 b 200IU, thymus peptide 1 0mg) of the present invention are added starch 300 grams, add 40 gram starch slurries behind the mixing and be mixed and made into soft material, 14 mesh sieves are granulated, 37 ℃ of vacuum dryings 24 hours, add magnesium stearate 2.5 grams and Sodium Hydroxymethyl Stalcs 5 gram mixings behind the 14 mesh sieve granulate, 1000 of tablettings.
Embodiment 21: the preparation of pharmaceutical composition tablet of the present invention
Freeze dried pharmaceutical composition 20 grams (every contains recombinant human interferon alpha 2 b 200IU, thymosin 20mg) of the present invention are added starch 300 grams, add 40 gram starch slurries behind the mixing and be mixed and made into soft material, 14 mesh sieves are granulated, 37 ℃ of vacuum dryings 24 hours, add magnesium stearate 2.5 grams and Sodium Hydroxymethyl Stalcs 5 gram mixings behind the 14 mesh sieve granulate, 1000 of tablettings.
Embodiment 22: the preparation of pharmaceutical composition nasal drop of the present invention
Get sodium chloride 9 grams, methyl hydroxybenzoate 0.2 gram, propylparaben 0.2 gram, hyaluronate sodium 0.3 gram, with water for injection dissolving back autoclaving.Get gelatin 5 gram adding water for injection room temperatures and put 2 hours, heating in water bath melts, autoclaving.Pharmaceutical composition of the present invention (final concentration contains recombinant human interferon alpha 2 b 100IU/ml, thymus peptide 1 0mg/ml) is added mixing in above two kinds of solution, and aseptic filtration is mended sterilized water for injection to 1000ml mixing, packing.
Embodiment 23: the preparation of pharmaceutical composition nasal drop of the present invention
Get sodium chloride 9 grams, methyl hydroxybenzoate 0.2 gram, propylparaben 0.2 gram, hyaluronate sodium 0.3 gram, with water for injection dissolving back autoclaving.Get gelatin 5 gram adding water for injection room temperatures and put 2 hours, heating in water bath melts, autoclaving.Pharmaceutical composition of the present invention (final concentration contains recombinant human interferon alpha 2 b 100IU/ml, thymosin 20mg/ml) is added mixing in above two kinds of solution, and aseptic filtration is mended sterilized water for injection to 1000ml mixing, packing.
Embodiment 24: the preparation of pharmaceutical composition nasal drop of the present invention
Get sodium chloride 9 grams, methyl hydroxybenzoate 0.2 gram, propylparaben 0.2 gram, hyaluronate sodium 0.3 gram, with water for injection dissolving back autoclaving.Get gelatin 5 gram adding water for injection room temperatures and put 2 hours, heating in water bath melts, autoclaving.Pharmaceutical composition of the present invention (final concentration contains recombinant human interferon alpha 2 b 200IU/ml, thymus peptide 1 0mg/ml) is added mixing in above two kinds of solution, and aseptic filtration is mended sterilized water for injection to 1000ml mixing, packing.
Embodiment 25: the preparation of pharmaceutical composition nasal drop of the present invention
Get sodium chloride 9 grams, methyl hydroxybenzoate 0.2 gram, propylparaben 0.2 gram, hyaluronate sodium 0.3 gram, with water for injection dissolving back autoclaving.Get gelatin 5 gram adding water for injection room temperatures and put 2 hours, heating in water bath melts, autoclaving.Pharmaceutical composition of the present invention (final concentration contains recombinant human interferon alpha 2 b 200IU/ml, thymosin 20mg/ml) is added mixing in above two kinds of solution, and aseptic filtration is mended sterilized water for injection to 1000ml mixing, packing.
Claims (11)
1. a pharmaceutical composition comprises recombinant human interferon-alpha, thymus bioactive peptide and pharmaceutically acceptable adjuvant and/or excipient.
2. the described pharmaceutical composition of claim 1 is characterized in that recombinant human interferon-alpha: 50IU-200 ten thousand every milliliter of IU or every preparation unit; Thymus bioactive peptide: every milliliter of 5-100mg or every preparation unit, every milliliter of preferred 5-20mg or every preparation unit.
3. the described pharmaceutical composition of claim 1 is characterized in that, the dosage form of this pharmaceutical composition is spray, freeze dried injection, suppository, tablet, capsule, nasal drop.
4. the described pharmaceutical composition of claim 3 is characterized in that, this spray comprises recombinant human interferon-alpha: 50IU-50 ten thousand IU/mL; Thymus bioactive peptide: 5-50mg/mL, preferred 5-20mg/mL.
5. the described pharmaceutical composition of claim 3 is characterized in that, this freeze dried injection comprises recombinant human interferon-alpha: 1,000,000 IU-200, ten thousand IU/mL; Thymus bioactive peptide: 5-100mg/mL, preferred 5-20mg/mL.
6. the described pharmaceutical composition of claim 3 is characterized in that, this suppository comprises recombinant human interferon-alpha: ten thousand IU/ pieces of 10,000 IU-100; Thymus bioactive peptide: 5-50mg/ piece, preferred 5-20mg/ piece.
7. the described pharmaceutical composition of claim 3 is characterized in that, this tablet comprises recombinant human interferon-alpha: 50IU-50 ten thousand IU/ sheets; Thymus bioactive peptide: 5-50mg/ sheet, preferred 5-20mg/ sheet.
8. the described pharmaceutical composition of claim 3 is characterized in that, this capsule comprises recombinant human interferon-alpha: 50IU-50 ten thousand IU/ grains; Thymus bioactive peptide: 5-50mg/ grain, preferred 5-20mg/ grain.
9. the described pharmaceutical composition of claim 3 is characterized in that, this nasal drop comprises recombinant human interferon-alpha: 50IU-50 ten thousand IU/mL; Thymus bioactive peptide: 5-50mg/mL, preferred 5-20mg/mL.
10. the pharmaceutical composition of claim 1-9, wherein recombinant human interferon-alpha is a recombinant human interferon alpha 2 b.
11. the application in the pharmaceutical composition that is combined in preparation claim 1-10 of recombinant human interferon-alpha and thymus active polypeptide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510081539 CN1887346A (en) | 2005-06-28 | 2005-06-28 | Recombinant human interferon-alpha-thymulin medicine composition and its applied prepn form |
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| CN 200510081539 CN1887346A (en) | 2005-06-28 | 2005-06-28 | Recombinant human interferon-alpha-thymulin medicine composition and its applied prepn form |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105658205A (en) * | 2013-12-20 | 2016-06-08 | 迪斯法国际私人有限责任公司 | Dry enema product |
| CN111671886A (en) * | 2020-03-05 | 2020-09-18 | 上海甘翼生物医药科技有限公司 | Pharmaceutical composition for preventing high-risk susceptible people from infecting coronavirus or generating coronavirus infection disease and application of pharmaceutical composition |
-
2005
- 2005-06-28 CN CN 200510081539 patent/CN1887346A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105658205A (en) * | 2013-12-20 | 2016-06-08 | 迪斯法国际私人有限责任公司 | Dry enema product |
| CN111671886A (en) * | 2020-03-05 | 2020-09-18 | 上海甘翼生物医药科技有限公司 | Pharmaceutical composition for preventing high-risk susceptible people from infecting coronavirus or generating coronavirus infection disease and application of pharmaceutical composition |
| CN111671886B (en) * | 2020-03-05 | 2022-11-15 | 上海甘翼生物医药科技有限公司 | Pharmaceutical composition for preventing high-risk susceptible people from infecting coronavirus or generating coronavirus infection disease and application of pharmaceutical composition |
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