CN100337684C - Thymic pentapeptide aqua prepn and its prepn process and application - Google Patents
Thymic pentapeptide aqua prepn and its prepn process and application Download PDFInfo
- Publication number
- CN100337684C CN100337684C CNB2005101029915A CN200510102991A CN100337684C CN 100337684 C CN100337684 C CN 100337684C CN B2005101029915 A CNB2005101029915 A CN B2005101029915A CN 200510102991 A CN200510102991 A CN 200510102991A CN 100337684 C CN100337684 C CN 100337684C
- Authority
- CN
- China
- Prior art keywords
- preparation
- thymopentin
- pentapeptide
- thymic
- clarity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Abstract
The present invention relates to a water solution preparation of thymic pentapeptide, a preparation process and the application of the water solution preparation to the preparation of medicine for treating chronic viral hepatitis, tumors and other immunological diseases. The preparation is composed of thymic pentapeptide, medicinal auxiliary materials and water, wherein the specification of the thymic pentapeptide can be from 0.1 to 1000 mg/pipe; the volume can be from 0.1 to 500 ml; the auxiliary materials are selected from and not limited by carbohydrates, such as mannitol, or polyethylene glycol, etc., twenty kinds of human amino acid, such as all kinds of cyclodextrin, glycine, etc., low molecular dextran, poloxamer, buffering salts, such as phosphate, or acetate, etc. The preparation process of the preparation comprises the steps of solution compounding, disinfection, separated packing, tamponage, packing, etc. The water solution preparation has the characteristics of good stability and convenient preparation, and better keeps the structure and the activity of the thymic pentapeptide; the water solution preparation also has the characteristic of wide application prospect in the preparation of medicine for treating chronic viral hepatitis, tumors and other immunological diseases.
Description
Technical field
The present invention relates to medicine and formulation art thereof.The core of invention has been to provide a kind of novel formulation, its preparation method of Thymopentin and has been used for the treatment of application in the medicine of chronic viral hepatitis, tumor and other immune disease in preparation.
Background technology
G.Goldstein had synthesized Thymopentin (thymopentin TP-5) in 1979, five amino acid residue in its structure and thymopoietin (Thymopoietin, TP) the 32-36 position order in 49 aminoacid is identical, and prove that it is the functional activity fragment of TP, promptly it has the similar physiologically active of TP.
Thymopentin (TP-5) is a kind of immunomodulator, and body's immunity is had dual regulation, makes too high or too low immunoreation be tending towards normal.Its main mechanism of action comprises the following aspects: can inducing T cell differentiation, optionally induce the prothymocyte of Thy-1 to be converted into the T cell of Thy-1+, its T cell differentiation effect is by the mediation that raises of CAMP level in the cell.It can promptly combine with the special receptor 2 of T cell ripe periphery blood T cell effect, makes CAMP level rising in the born of the same parents, causes a series of intramicellar reaction, thereby reaches immunoregulatory effect.Under the normal body state; Thymopentin (TP-5) manifests immunostimulation; significantly improve the E-rosette formation rate and the conversion ratio of splenocyte; all by enhanced effect, can increase the antibody forming cell of IgM type and IgA type to the different phase of for the first time or again secondary response of immunne response.Thymopentin (TP-5) can strengthen the phagocytic activity of macrophage, increases the enzymatic activity and the phagocytic function of polymorph neutrophile leucocytes, and rising circulating antibody content strengthens hematid immunity function.It can activate CD4 and CD8 positive cell, makes single-minded Tc cell survival keep the longer time, also can activate the Th cell simultaneously, induces the function of Ts cell.
Clinically, Thymopentin (TP-5) demonstrates good immune dual regulation, is mainly reflected in it to the regulating action of thymus and to the regulating action of immunologic hypofunction and autoimmune disease.For because the atrophy of thymus gland that age and various stress damage cause, TP-5 can promote the Growth and Differentiation of thymocyte cell, regulates the thymus function that goes down.For by chemicotherapy, the immunologic hypofunction that operation wound etc. cause has significant protective effect.In treatment rheumatic arthritis, lupus erythematosus, autoimmune diseasees such as vitiligo have good curative effect too.Infection such as the repeated relapsing herpes labialis (perhaps herpes zoster and herpes simplex etc.) that can not effectively control for chronic hepatitis, type ii diabetes, severe infections or antibiotic simultaneously have curative effect preferably.The toxic and side effects of Thymopentin (TP-5) is very little simultaneously, can not interact with many drug combinations.Compare with normally used animal thymus extract formulation, Thymopentin (TP-5) all has sizable advantage aspect active constituent content and the mode of production and the quality control, is a kind of successful immunomodulator.
Thymopentin (TP-5) is paid close attention to by people very early as a kind of immunomodulator with development prospect.It went on the market in 1985 in Italy, and commodity are called Timunox, also had the man pharmaceutical factory of number researching and developing in the U.S., and was examined by U.S. FDA.
But, be limited to the restriction of indexs such as stability, the lyophilized injectable powder of Thymopentin is only arranged in the market, this dosage form needs to dissolve in use, has also increased the chance of medicine pollution when having increased operating procedure.The present invention has formulated the aqueous solution preparation of Thymopentin just at the single situation of present Thymopentin dosage form, has solved the stability problem of Thymopentin in aqueous solution, and this is a main purpose of the present invention.
Summary of the invention
Mentality of designing of the present invention, research contents and technical scheme:
Main contents of the present invention comprise development, study on the stability and three parts of pharmaceutical research of preparation process.Wherein, the stability of Thymopentin in aqueous solution preparation is the problem that needs emphasis to solve.
According to the requirement of human aqueous solution preparation research, this solution type preparation should be a solution clear and bright, safe, harmless, good stability.Solvent can be that aqueous also can be non-aqueous, and what aqueous solvent was the most frequently used is water for injection.According to the characteristics of active medicine, can select various pharmaceutic adjuvants, as osmotic pressure regulator, solubilizing agent, antioxidant, cosolvent, pH value regulator or the like.In conjunction with the characteristics of Thymopentin, we have mainly considered to have used following adjuvant: osmotic pressure regulator, pH value regulator, solubilizing agent, antioxidant and antiseptic.
Optionally osmotic pressure regulator can be but be not limited only to inorganic salts chemical compound such as sodium chloride; Optionally the pH value regulator can be but be not limited only to phosphate buffer, acetate buffer solution, citrate buffer solution etc.; Optionally solubilizing agent or cosolvent can be but be not limited only to 20 kinds of human amino acids such as glycine and salt (as cysteine, leucine, methionine etc.) thereof, various cyclodextrin, glycerol carbohydrate, various cyclodextrin, low molecular dextran, poloxamers or the like such as (perhaps sorbitol, Polyethylene Glycol, propylene glycol); Optionally antioxidant can be but be not limited only to ethylenediaminetetraacetic acid and salt thereof, ascorbic acid, citric acid, cysteine, glutathion, methionine or the like; Available antiseptic can be but be not limited only to cinnamyl alcohol, formic acid or the like.
Show that through a large amount of orthogonal tests above-mentioned adjuvant has good stablizing effect to Thymopentin.Wherein, preferred pH value regulator is that phosphate buffer, preferred solubilizing agent are cyclodextrin compounds, and preferred osmotic pressure regulator is a sodium chloride, and preferred anti-oxidants is the EDTA disodium.
Aspect Thymopentin and the supplementary product consumption composition, Thymopentin can be that 0.1-1000mg/ props up in prescription, for example 0.5,1,2,5,10,20,50,100,250,500mg/ props up.The volume of unit formulation can be 0.1-500ml.
A preferred prescribed regimen is: the disodiumedetate (EDTA) of 0.5-250mg Thymopentin, 5-50mmol/L phosphate buffer, 0.5-10mmol/L, the sodium chloride of 0.5-5%.Preferred on this basis scheme is: the disodiumedetate (EDTA) of 0.5-10mg Thymopentin, 10-30mmol/L phosphate buffer, 0.5-5mmol/L, the sodium chloride of 0.5-2%.Most preferred scheme is: the disodiumedetate (EDTA) of 1mg Thymopentin, 20mmol/L phosphate buffer, 1mmol/L, 0.7% sodium chloride, the preparation specification is 1mg: 1ml.
Another preferred prescribed regimen is: the disodiumedetate (EDTA) of 0.5-250mg Thymopentin, 5-50mmol/L phosphate buffer, 0.5-10mmol/L, the sodium chloride of 0.5-5%, 0.1-10% hydroxypropyl beta cyclodextrin.On this basis, preferred component solutions is: the disodiumedetate (EDTA) of 0.5-10mg Thymopentin, 10-30mmol/L phosphate buffer, 0.5-5mmol/L, the sodium chloride of 0.5-2%, 0.5-5% hydroxypropyl beta cyclodextrin.Most preferred component solutions is: the disodiumedetate (EDTA) of 1mg Thymopentin, 20mmol/L phosphate buffer, 1mmol/L, 0.7% sodium chloride, 2% hydroxypropyl beta cyclodextrin, the preparation specification is 1mg: 1ml.
Above-mentioned preparation prescription can be prepared by following technology:
(1) under 100 grades of laminar flows, takes by weighing required sodium chloride, 12 water sodium hydrogen phosphates, 2 water sodium dihydrogen phosphate disodiumedetates, in the suitable container of packing into, add the amount of calculation sterilized water for injection dissolving is used immediately by inventory.
(2) the recipe quantity Thymopentin is added buffer, shake up after the dissolving, ultrafiltration post ultrafiltration depyrogenation, the filter that the reuse high pressure steam sterilization is crossed (the double-deck filter membrane of 0.22 μ m, 0.45 μ m) filtration sterilization is sealed, and prepares packing.
(3) adjust dosage with sterilized water for injection by every 1ml earlier before the packing, after dose titration is qualified, the liquid packing of changing dressings.After jumping a queue entirely, medicine bottle is sent into the bottle track, carry out gland.
(4) start Cover-rolling machine, medicine bottle is with the rotating disk injection, and aluminium lid adds on the medicine bottle through track, and is locked by head.Rolling lid back aluminium lid should be tightly, neat in edge.
So far, the design and the research of preparation process thereof has been finished in our invention, begins to investigate stability of formulation.Experiment with sample from the prepared product of embodiment 1.
According to corresponding research requirement, we have mainly investigated the clarity of appearance character, pH value, solution and color, related substance, content, clarity test, bacterial endotoxin and aseptic stability study.Influence factor's test, accelerated test and long term test have mainly been carried out.
It is high temperature and strong illumination that the influence factor tests main investigation factor.
Strong illumination experiment: test sample is placed in the clarity detector, is to place 10 days under the condition of 4000lx ± 500lx in intensity of illumination, in sampling in the 5th and the 10th day, detects by stable high spot reviews project, and compares with 0 day.Result such as table 1.The result shows that this product pH value after illumination obviously descends, and related substance increases, and content obviously descends, and all other indexs do not have significant change, so this product answers shading to preserve.
Table 1 exposure experiments to light study on the stability result
| Lot number | Time (my god) | The investigation project | |||||
| Appearance character | The pH value | Clarity | Clarity and color | Related substance (%) | Content (%) | ||
| 01 | 0 | Achromatism and clarity | 7.05 | Up to specification | Clarify colourless | 0.29 | 99.82 |
| 5 | Achromatism and clarity | 5.85 | Up to specification | Clarify colourless | 0.50 | 82.35 | |
| 10 | Achromatism and clarity | 5.68 | Up to specification | Clarify colourless | 1.15 | 81.04 | |
High temperature experiment: test sample is placed glass dish, placed 10 days down at 60 ℃ respectively.During this period,, detect by stable high spot reviews project respectively at sampling in the 5th and the 10th day, and with 0 day relatively.Testing result sees Table 2.
Table 2 hot test study on the stability result (60 ℃)
| Lot number | Time (my god) | The investigation project | |||||
| Appearance character | The pH value | Clarity | The clarity of solution and color | Related substance (%) | Content (%) | ||
| 01 | 0 | Achromatism and clarity | 7.05 | Up to specification | Clarify colourless | 0.29 | 99.82 |
| 5 | Achromatism and clarity | 6.20 | Up to specification | Clarify colourless | 4.01 | 81.25 | |
| 10 | Achromatism and clarity | 6.07 | Up to specification | Clarify colourless | 4.12 | 78.14 | |
60 ℃ of experimental results of high temperature show: this product is behind 60 ℃ of high temperature 10 days, and pH value obviously descends, and related substance obviously increases, and content obviously descends, and all other indexs do not have significant change.Carry out 40 ℃ of tests of high temperature according to above some variation event.See Table 3.
Table 3 hot test study on the stability result (40 ℃)
| Lot number | Time (my god) | The investigation project | |||||
| Appearance character | The pH value | Clarity | The clarity of solution and color | Related substance (%) | Content (%) | ||
| 01 | 0 | Achromatism and clarity | 7.05 | Up to specification | Clarify colourless | 0.29 | 99.78 |
| 5 | Achromatism and clarity | 6.48 | Up to specification | Clarify colourless | 0.65 | 93.20 | |
| 10 | Achromatism and clarity | 6.30 | Up to specification | Clarify colourless | 1.50 | 92.52 | |
40 ℃ of experimental results of high temperature show: this product is behind 40 ℃ of high temperature 10 days, and pH value descends, and related substance increases, and content descends, according to above some change so carry out 25 ℃ of tests.The results are shown in Table 4.
25 ℃ of tests of table 4 study on the stability result
| Lot number | Time (my god) | The investigation project | |||||
| Appearance character | The pH value | Clarity | The clarity of solution and color | Related substance (%) | Content (%) | ||
| 01 | 0 | Achromatism and clarity | 7.05 | Up to specification | Clarify colourless | 0.29 | 99.78 |
| 5 | Achromatism and clarity | 6.94 | Up to specification | Clarify colourless | 0.52 | 99.18 | |
| 10 | Achromatism and clarity | 6.89 | Up to specification | Clarify colourless | 1.33 | 98.93 | |
Show in result under 25 ℃ of experiment conditions: this product is after 25 ℃ of conditions are placed 10 days, and pH value descends, and related substance slightly increases, and content has decline slightly; Belong to the preparation responsive especially to temperature so can determine this product, accelerated tests can be carried out under the condition of RH 60 ± 10% 25 ℃ ± 2 ℃ of temperature; Long-term experiment can carry out under 2 ℃ of-10 ℃ of conditions of temperature.
Accelerated test: this product is placed 25 ℃ ± 2 ℃ of temperature, in the environment of RH 60 ± 10%, placed 6 months, respectively at 1st month, 2 months, 3 months, 6 samplings at the end of month detected by stable high spot reviews project.Result of the test sees Table 5.
Table 5 accelerated test is investigated result's (25 ℃ ± 2 ℃, RH60 ± 10%)
| Lot number | Month | The investigation project | ||||||
| Appearance character | PH value | Clarity | Related substance (%) | Endotoxin | Aseptic | Content (%) | ||
| 02 | 0 | Achromatism and clarity | 7.05 | Up to specification | 0.31 | Up to specification | Up to specification | 99.64 |
| 1 | Achromatism and clarity | 6.21 | Up to specification | 9.88 | - | - | 91.90 | |
| 2 | The solution muddiness | 5.46 | The solution muddiness | 15.47 | - | - | 85.47 | |
| 3 | The solution muddiness | 4.59 | The solution muddiness | 19.42 | - | - | 81.52 | |
| 6 | The solution muddiness | 3.99 | The solution muddiness | 29.33 | - | - | 71.45 | |
Accelerated test result shows that the Thymopentin aqueous solution was placed 6 months with this understanding, and pH value descends, and related substance increases, and content descends and illustrates that this product belongs to the preparation responsive especially to temperature, need put cold place and preserve.
Long term test: this product packing is placed under 2 ℃ of-10 ℃ of conditions of temperature, placed 6 months, sampling in per 3 months once detected by stable high spot reviews project respectively at 0 month, 3 months, 6 months.Result of the test sees Table 6.After this continued to investigate respectively at 9 months, 12 months, 18 months, 24 months, 36 months.
Table 6 long term test is investigated result's (2 ℃-10 ℃)
| Lot number | Month | The investigation project | |||||||
| Appearance character | Clarity and color | PH value | Clarity | Related substance (%) | Endotoxin | Aseptic | Content (%) | ||
| 02 | 0 | Achromatism and clarity | Clarify colourless | 7.00 | Up to specification | 0.29 | Up to specification | Up to specification | 100.0 |
| 3 | Achromatism and clarity | Clarify colourless | 7.07 | Up to specification | 0.31 | Up to specification | Up to specification | 100.0 | |
| 6 | Achromatism and clarity | Clarify colourless | 7.13 | Up to specification | 0.30 | Up to specification | Up to specification | 100.0 | |
| 9 | Achromatism and clarity | Clarify colourless | 7.15 | Up to specification | 0.32 | Up to specification | Up to specification | 100.0 | |
| 03 | 0 | Achromatism and clarity | Clarify colourless | 7.08 | Up to specification | 0.30 | Up to specification | Up to specification | 99.83 |
| 3 | Achromatism and clarity | Clarify colourless | 7.11 | Up to specification | 0.33 | Up to specification | Up to specification | 99.80 | |
| 6 | Achromatism and clarity | Clarify colourless | 7.75 | Up to specification | 0.33 | Up to specification | Up to specification | 99.79 | |
| 9 | Achromatism and clarity | Clarify colourless | 7.82 | Up to specification | 0.34 | Up to specification | Up to specification | 99.79 | |
The result shows that the Thymopentin aqueous solution was placed 6 months under the long term test condition, every index does not all have obvious change, illustrates that this product has good stability.
The stability test conclusion: influence factor's result of the test shows, the Thymopentin aqueous solution transfers in illumination, in 40 ℃, 25 ℃ conditions of high temperature (60 ℃) that the postpone pH value descends, content descends, related substance increases; Placed 6 months in accelerated test condition (25 ℃ ± 2 ℃, RH 60 ± 10%), pH value descends, content descends, related substance increases; Placed 6 months in long term test condition (2 ℃-10 ℃), every index does not all have obvious change.Determine that this product answers shading, preserve at Leng Chu (2-10 ℃).02 batch sample content detection liquid phase collection of illustrative plates in the time of 9 months is seen Figure of description 1.
Another part content of the present invention is to investigate the pharmacology of described aqueous solution ejection preparation.The main purpose of pharmaceutical research is the biological activity of more this dosage form and existing Thymopentin freeze-dried powder dosage form.Thymopentin has immunoloregulation function widely, and this is not the problem that the present invention will illustrate.What we need solve only is the activity whether novel formulation provided by the invention has Thymopentin, infers said preparation when the indication of treatment Thymopentin and the equivalence of existing preparation with this, and determines the said preparation practicality with this.We have adopted the E rosette test for this reason.
Thymopentin is tested the influence of E rosette formation rate:
Material and reagent:
Porcine thymus, sheep anti blood coagulation, culture medium etc.
Medicine and numbering:
No. 01 sample, the Thymopentin lyophilized powder of embodiment of the invention preparation.
Experimental procedure:
Fresh pig thymus cleans and makes the lymphocyte suspension through grinding, and being diluted to concentration after the cleaning is 3 * 10
6-5 * 10
6Individual cell (work)/milliliter.Get the sheep anti blood coagulation, washing, centrifugal back dilution counting make it final concentration and are to take off 50 times of E receptor T lymphocyte concentration.Thymopentin aqueous solution and lyophilized powder are diluted to the solution of 20ug/ml with Hank ' s washing liquid.
Get 6 test tubes, 2 add Hank ' s washing liquid and without the T lymphocyte that takes off the E receptor, and 2 add Hank ' s washing liquid and take off E receptor T lymphocyte suspension, 2 add sample and take off E receptor T lymphocyte suspension, and 37 ℃ of insulations are after 60 minutes, and every pipe adds sheep erythrocyte suspension, shake up, centrifugal, spend the night.Get supernatant, fixing, dyeing, the cell number (in conjunction with the lymphocyte of 3 above sheep red blood cells) that microscopically statistics E rosette forms, result such as following table 7.
Table 7. Thymopentin to the influence of E rosette formation rate (mean ± standard deviation, n=6)
| Become footing/100 lymphocytes | Average one-tenth knot rate (%) | |
| Negative control | 40.2±3.7 | 40.2 |
| No. 01 sample | 61.2±4.5* | 61.2 |
| The freeze-dried powder contrast | 59.7±3.1* | 59.7 |
Annotate: * represent with negative control than p＜0.01.
The result shows, Thymopentin aqueous solution provided by the invention and traditional lyophilized injectable powder have same immunoloregulation function.
In sum, the invention provides the novel form of a Thymopentin, this dosage form manufacturing technique is simpler than existing freeze-dried powder agent producing process, is easy to amplify on producing, and is with the obvious advantage, is convenient to the realization of industrialization; Simultaneously, good as claim and the described dosage form stability of description aspect biological activity and preparation stability, can long term storage, it is active identical with existing lyophilized injectable powder.Therefore the present invention has embodied the patent key element of novelty, creativeness and practicality well.
The specific embodiment
For the implementation process of this patent is described better, we are listed below embodiment.Need to prove that cited embodiment is one of imbody of thinking of the present invention and spirit, is not the scope restriction to the patent of invention description, more is not the refinement to claim.Under thinking of the present invention, the aqueous products (injection, spray, drop etc.) of the Thymopentin that any this patent is described all should be included in the scope of this patent.
The preparation of embodiment 1, the described pharmaceutical preparation of claim 7
Sodium chloride 7.0g, sodium hydrogen phosphate (containing 12 water of crystallization) 4.37g, sodium dihydrogen phosphate (containing 2 water of crystallization) 1.22g, disodiumedetate 0.64g, Thymopentin 1.0g decided in accurate title, be dissolved in water for injection, fixed molten at last to 1000ml, be distributed into 1000 with the 2ml cillin bottle.Final specification is that 1mg/ props up.According to this 3 batches of production sample of writing out a prescription altogether, numbering is respectively 01,02,03.Operation sequence is described execution to specifications.
The preparation of embodiment 2, the described pharmaceutical preparation of claim 10
Sodium chloride 7.0g, sodium hydrogen phosphate (containing 12 water of crystallization) 4.37g, sodium dihydrogen phosphate (containing 2 water of crystallization) 1.22g, disodiumedetate 0.64g, Thymopentin 1.0g, hydroxypropyl beta cyclodextrin 20g decided in accurate title, be dissolved in water for injection, fixed molten at last to 1000ml, be distributed into 1000 with the 2ml cillin bottle.Final specification is that 1mg/ props up.According to this 1 batch of production sample of writing out a prescription altogether, numbering 04.Operation sequence is described execution to specifications.
Claims (5)
1, a kind of aqueous solution preparation of Thymopentin, it is mainly formed: the disodiumedetate of 0.5-10mg Thymopentin, 10-30mmol/L phosphate buffer, 0.5-5mmol/L, the sodium chloride of 0.5-2% are prepared into the preparation that unit volume is 0.1-500ml.
2, preparation as claimed in claim 1, it is mainly formed and is: the disodiumedetate of 1mg Thymopentin, 20mmol/L phosphate buffer, 1mmol/L, 0.7% sodium chloride, being prepared into specification is the preparation that 1mg: 1ml/ props up.
3, preparation as claimed in claim 1, it is mainly formed: the disodiumedetate of 0.5-10mg Thymopentin, 10-30mmol/L phosphate buffer, 0.5-5mmol/L, the sodium chloride of 0.5-2%, 0.5-5% hydroxypropyl beta cyclodextrin are prepared into the preparation that unit volume is 0.1-500ml.
4, preparation as claimed in claim 3, it is mainly formed: the disodiumedetate of 1mg Thymopentin, 20mmol/L phosphate buffer, 1mmol/L, 0.7% sodium chloride, 2% hydroxypropyl beta cyclodextrin are prepared into the preparation that specification 1mg: 1ml/ props up.
5, any described preparation of claim 1-4 is used for the treatment of application in the medicine of acute and chronic viral hepatitis, tumor and other immune disease in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101029915A CN100337684C (en) | 2005-05-11 | 2005-09-16 | Thymic pentapeptide aqua prepn and its prepn process and application |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510069081 | 2005-05-11 | ||
| CN200510069081.1 | 2005-05-11 | ||
| CNB2005101029915A CN100337684C (en) | 2005-05-11 | 2005-09-16 | Thymic pentapeptide aqua prepn and its prepn process and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1739786A CN1739786A (en) | 2006-03-01 |
| CN100337684C true CN100337684C (en) | 2007-09-19 |
Family
ID=36092411
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005101029915A Active CN100337684C (en) | 2005-05-11 | 2005-09-16 | Thymic pentapeptide aqua prepn and its prepn process and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100337684C (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101318011B (en) * | 2007-04-17 | 2012-03-14 | 海南中和药业股份有限公司 | Pentapeptide nose spraying agent for thymus gland, preparation method and application thereof |
| CN102380088A (en) * | 2010-08-31 | 2012-03-21 | 海南中化联合制药工业股份有限公司 | Prescription and preparation method of thymopeptide-5 injection |
| CN102321156B (en) * | 2011-09-02 | 2012-08-15 | 周晓东 | Novel thymopentin compound and composition powder injection thereof |
| CN102488884B (en) * | 2011-12-14 | 2014-01-01 | 中国人民解放军第三0二医院 | Thymopoietin for large dosage injection and application thereof for treating severe hepatitis |
| CN102764424B (en) * | 2012-08-20 | 2013-12-18 | 湖北济生医药有限公司 | Drug composition of thymopentin composed of five kinds of amino acids and preparation method thereof |
| CN103315949B (en) * | 2013-05-09 | 2015-04-08 | 成都力思特药物研究有限公司 | Thymopent aqueous solution preparation and use thereof |
| CN105012232B (en) * | 2015-08-14 | 2017-09-05 | 北京世桥生物制药有限公司 | A kind of thymus gland pentapeptide injection and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0063328A2 (en) * | 1981-04-10 | 1982-10-27 | Eisai Co., Ltd. | Compositions containing secretin and method for preventing the adsorption of secretin |
| WO1989005347A1 (en) * | 1987-12-10 | 1989-06-15 | Invitron Corporation | Method to solubilize tissue plasminogen activator |
| US5140010A (en) * | 1989-09-28 | 1992-08-18 | Immunobiology Research Institute | Stabilized aqueous formulations of thymopentin |
| CN1118143A (en) * | 1993-02-23 | 1996-03-06 | 基因技术股份有限公司 | Excipient stabilization of polypeptides treated with organic solvents |
| CN1402640A (en) * | 1999-10-04 | 2003-03-12 | 希龙公司 | Stabilized liquid polypeptide-confg. pharmaceutical compositions |
| CN1409758A (en) * | 1999-12-14 | 2003-04-09 | 热生物之星公司 | Stabilizing diluent for polypeptides and antigens |
-
2005
- 2005-09-16 CN CNB2005101029915A patent/CN100337684C/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0063328A2 (en) * | 1981-04-10 | 1982-10-27 | Eisai Co., Ltd. | Compositions containing secretin and method for preventing the adsorption of secretin |
| WO1989005347A1 (en) * | 1987-12-10 | 1989-06-15 | Invitron Corporation | Method to solubilize tissue plasminogen activator |
| US5140010A (en) * | 1989-09-28 | 1992-08-18 | Immunobiology Research Institute | Stabilized aqueous formulations of thymopentin |
| CN1118143A (en) * | 1993-02-23 | 1996-03-06 | 基因技术股份有限公司 | Excipient stabilization of polypeptides treated with organic solvents |
| CN1402640A (en) * | 1999-10-04 | 2003-03-12 | 希龙公司 | Stabilized liquid polypeptide-confg. pharmaceutical compositions |
| CN1409758A (en) * | 1999-12-14 | 2003-04-09 | 热生物之星公司 | Stabilizing diluent for polypeptides and antigens |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1739786A (en) | 2006-03-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100337684C (en) | Thymic pentapeptide aqua prepn and its prepn process and application | |
| Baxby et al. | Human cryptosporidiosis: a possible case of hospital cross infection. | |
| CN1047307C (en) | Pharmaceutical compositions for the treatment of hepatitis B virus (HBV) infection | |
| Munster et al. | The effect of antibiotics on cell-mediated immunity | |
| Hay et al. | The appearance of migration inhibition factor and a mitogen in lymph draining tuberculin reactions | |
| Moore et al. | PHA-induced lymphocyte transformations in leucocyte cultures from malarious, malnourished and control Gambian children | |
| CN101683519B (en) | Composition of thymic peptide alpha 1 and thymopeptide-5 and preparation method thereof | |
| CN100342909C (en) | Thymosin alpha-1 aqua prepn and its prepn process and application | |
| CN1739505A (en) | L-ornidazole injection prepn | |
| CN1259041C (en) | Bromhexine Hydrochloride aseptic freeze-drying formulation for injection and its preparation method | |
| Hammond et al. | Antigen-Enhanced Glucosamine Incorporation by Peritoneal Macrophages in Cell-Mediated Hypersensitivity: I. Studies on Biology and Mechanism | |
| CN100502944C (en) | Asparaginase injection its preparing method and use | |
| CN1748785A (en) | Water solution preparation of reducing type glutathione, its preparing method and use | |
| CN1404827A (en) | Tiopronin preparation | |
| Ben‐David et al. | HL‐A antigen changes in patients treated with chloramphenicol | |
| CN110327284B (en) | Cefodizime sodium for injection and preparation method thereof | |
| KOPP et al. | " Acquired" agammaglobulinemia with defective delayed hypersensitivity | |
| CN100336557C (en) | Somatostation a aqua prepn and its prepn process and application | |
| CN1802172A (en) | Therapeutic composition for autoimmune conditions | |
| CN115919831B (en) | Application of benzoate compound in inhibiting activity of uric acid transporter 1 and preparing medicament for treating hyperuricemia | |
| Kirchner et al. | Dissociation of in vitro lymphocyte transformation from production of a mononuclear leucocyte chemotactic factor in agammaglobulinemic chickens | |
| CN117085006B (en) | Application of salvianolic acid Y in preparing medicament for treating urticaria | |
| SHAHBAZIAN et al. | Influence of the level of dietary ethanol in mice with murine AIDS on resistance to Streptococcus pneumoniae | |
| Mikirova et al. | The levels of ascorbic acid in blood and mononuclear blood cells after Oral liposome-encapsulated and Oral non-encapsulated vitamin C supplementation, taken without and with IV hydrocortisone | |
| CN1235575C (en) | Coenzyme Q10 aseptic freee-drying preparation for injection and its preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| DD01 | Delivery of document by public notice |
Addressee: Wu Yanzhuo Document name: Notification of eligibility |
|
| DD01 | Delivery of document by public notice |