CN101318011A - Pentapeptide nose spraying agent for thymus gland, preparation method and application thereof - Google Patents
Pentapeptide nose spraying agent for thymus gland, preparation method and application thereof Download PDFInfo
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- CN101318011A CN101318011A CNA2007100981394A CN200710098139A CN101318011A CN 101318011 A CN101318011 A CN 101318011A CN A2007100981394 A CNA2007100981394 A CN A2007100981394A CN 200710098139 A CN200710098139 A CN 200710098139A CN 101318011 A CN101318011 A CN 101318011A
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Abstract
The invention relates to a nasal spraying agent of thymopentin, and a preparation method and applications thereof. The preparation is used in over18-year-old sufferers of chronic hepatitis B, various primary or secondary defect diseases of T cellular, certain autoimmune diseases, various diseases of low cellular immune function and adjutant therapy to tumours; the preparation consists of thymopentin, pharmaceutic adjuvant and water; the preparation method of the agent includes the steps of liquid preparation, degerming, split charging, stoppering, capping, package, etc. The medicament form overcomes the difficulty that polypeptide drugs are unsteady in water, thus keeping the activity of thymopentin well and having good stability; meanwhile, pain is not produced when the medicament form is used, thus being accepted by the general consumers.
Description
Technical field:
The present invention relates to a kind of pharmaceutical preparation and preparation technology thereof of intranasal administration of Thymopentin, also relate to said preparation and be used for the chronic hepatitis B patient more than 18 years old, various constitutional or Secondary cases T cell defect disease, some autoimmune disease (as rheumatoid arthritis, systemic lupus erythematosus (sle) etc.), the disease that various cellular immune function is low, the auxiliary treatment of tumor.
Background technology:
" thymopoietin II " is the single polypeptide chemical compound of separating from thymosin, form by 49 aminoacid, and the peptide chain fragment of wherein forming by 5 aminoacid, the whole physiological functions identical with " gland generates plain II " are arranged, so just this pentapeptide fragment is called " Thymopentin " (Thymopentin).
Thymopentin is a bidirectional immune regulator, and its pharmacological action is roughly the inducing T cell differentiation, promotes that the t lymphocyte subset mass-sending is educated, ripe and activatory function, and the ratio that can regulate the t lymphocyte subset group, makes it be tending towards normal.In body, Thymopentin promotes the T cell differentiation by improving the cAMP level, and with T cell-specific receptors bind, make that the GMP level improves in the cell, thereby bring out a series of intramicellar reactions, play the effect of regulating body's immunity.A large amount of " Thymopentin " clinical trials has all been finished in the without any side effects and untoward reaction of Thymopentin both at home and abroad.Patient is after the Thymopentin treatment, and through the hematology, every inspection indexs such as clinical biochemical, urinalysis all find no any bad variation or the toxic and side effects relevant with " Thymopentin ".Routine electrocardiogram, blood pressure, ophthalmology, hearing test also find no any bad variation or the side effect relevant with " Thymopentin ".During routine clinical is observed, after occurring in drug withdrawal on a small quantity slightly drowsiness, the asthenia of transference cure, there is not any untoward reaction yet, external report at least 50 routine patient's long-term prescriptions reach 1-2, all do not have the untoward reaction relevant with " Thymopentin ", and with ten surplus the class common drug common use also acomia incumbent what conflict mutually.Simultaneously, the Thymopentin molecule is less, is easy to chemosynthesis, and cost is lower, and the purity height does not contain macro-molecular protein.
The thymosin pentapeptide is applicable to that immunodeficiency symptoms is as virus, fungal infection etc. and drug-induced immune dysfunction disease, be used for aplastic anemia, thrombocytopenia, acute and chronic viral hepatitis, systemic lupus erythematosus (sle), pulmonary tuberculosis radiculitis, osteomyelitis, rheumatoid arthritis, epidemic cerebrospinal meningitis, chronic bronchitis, bronchial asthma, multiple joint are swollen, chronic intestinal infection, polyarthritis companion urethritis, oral mucosa lichen planus, children epilepsy, senile senilism, climacteric syndrome.
Along with people to the improving constantly of SARS understanding, notion healthy and immunocompetence has obtained universal propaganda, people begin to pay close attention to the immunologic function of oneself, pay close attention to the health of self, under the advocating of country, have added automatically in the middle of the motion of nationwide fitness programs.People look forward to using the psychology of the specific medicament that improves autoimmune function urgent day by day.
In sum, the thymosin pentapeptide has shown good two-way immunoregulatory effect clinically, is a kind of successful immunomodulator.
Existing in the market dosage form is thymus gland pentapeptide injection, thymopentin for injection (tp-5), and doctor and patient have brought many troubles when using these dosage forms, will stand injection pain, injection site infection etc. as sterilization, the patient of doctor's utensil before using.The present invention is according to the characteristics of Thymopentin, the preparation for preparing a kind of intranasal administration, exploration through filling a prescription simultaneously, find a kind of good prescription to form, thereby opened up a new route of administration, said preparation is not only easy to use, alleviated the misery when patient uses simultaneously, increased the compliance of patient's medication greatly, easilier accepted by extensive patients.
Summary of the invention:
The invention provides a kind of preparation of Thymopentin intranasal administration, said preparation comprises active component Thymopentin and necessary adjunct ingredient.
The preparation of intranasal administration of the present invention can be a drop, also can be spray, the preferred nasal spray of the present invention.
The present invention has selected following adjuvant to become: osmotic pressure regulator, absorption enhancer, stabilizing agent, buffer agent, antiseptic and antioxidant in conjunction with the characteristics of Thymopentin.
Wherein osmotic pressure regulator is selected from sodium chloride, glucose, glycerol, mannitol, sorbitol, sodium chloride, boric acid, glucose, Borax etc.
Absorption enhancer is selected from Fructus Citri Limoniae acids, salicylic acid, terpenoid, quintessence oil and lactone (as book lotus brain, Borneolum Syntheticum, Oleum Eucalypti and Rhizoma Chuanxiong, Elettaria cardamomum (L.) Maton etc.) etc.;
Stabilizing agent is selected from 20 kinds of human amino acids such as glycine, low molecular dextran, ethylenediaminetetraacetic acid, disodiumedetate, sodium ethylene diamine tetracetate calcium etc.;
Buffer agent is selected from phosphate, acetate, citrate, citric acid-sodium dihydrogen phosphate, citric acid-sodium hydrogen phosphate etc.;
Antiseptic is selected from benzyl alcohol, chlorobutanol, thimerosal, phenylmercuric nitrate, benzalkonium chloride, hibitane, phenoxyethanol, Nipagin ester, sorbic acid etc.;
Antioxidant is selected from sodium sulfite, sodium metabisulfite, cysteine, paddy cystine, ascorbic acid etc.
Through a large amount of screenings, the present invention has therefrom selected particularly preferred prescription and has formed.Wherein, preferred osmotic pressure regulator is that sodium chloride, preferred stabilizing agent are that disodiumedetate, preferred buffer salt are that citric acid-sodium dihydrogen phosphate, preferred absorption enhancer are that citric acid, preferred anti-oxidants are that sodium sulfite, preferred antibacterial are benzalkonium chlorides.
The present invention finds that through experimental verification its PH of preparation of the present invention is the most stable between 4.0～5.5 in addition.
Therefore, the most preferred prescription of the present invention is composed as follows:
It is as follows to write out a prescription:
Thymopentin: 25.0g
Sodium chloride: 7.5g
Citric acid monohydrate chemical compound: 1.7g
Sodium hydrogen phosphate two hydrates: 3.0g
This bundle oronain (50%): 0.2g
Add the injection water extremely: 1250ml
PH transfers to 4.0～5.5 and makes 500 bottles altogether
The preparation method of preparation of the present invention is as follows:
1, in 100,000 grades of clean areas, takes by weighing the above-mentioned supplementary material of recipe quantity to sterilization container;
2, be stirred well to dissolving fully behind an amount of water for injection of adding;
3, regulate pH value to 4.0 between 5.0 with the hydrochloric acid of 0.1M or sodium hydroxide;
4, adding to the full amount of water for injection;
5, be transferred in ten thousand grades of clean areas, through 0.22um microporous filter membrane fine straining; And measure content, pH value, medicinal liquid clarity etc.;
6, carry out fill after qualified, add pump, roll lid and add medicated cap;
7, examine entirely qualified after, labeling, the dress box.
Preparation of the present invention has outstanding stability.Following experimental result can illustrate excellent results of the present invention:
We mainly investigate inspections such as the clarity of appearance character, pH value, solution of pentapeptide nose spraying agent for thymus gland and color, related substance, content.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 test: test sample was positioned in high light 4500 ± 500lx environment 10 days, respectively at sampling in 5 days, 10 days, detects, and compared in 0 day by stable high spot reviews project.Related data sees Table 1:
The result is investigated in table 1 highlight test
The strong illumination result of the test shows: this product is when strong illumination, and each index slightly changes, and needs shading to preserve.
Hot test: test sample was positioned in the high temperature 60 degree environment 10 days, respectively at sampling in 5 days, 10 days, detects, and compared in 0 day by stable high spot reviews project.Related data sees Table 2:
The result is investigated in table 2 hot test
Hot test is the result show: this product is in hot environment, and its clarity, color are constant, and pH value, related substance, content all slightly change, and the compatibility of interior packaging material and medicinal liquid is better.
Accelerated test: this product is placed 40 degree environment, placed 3 months,, measure by stable high spot reviews project respectively at sampling in 0,1,2,3 month.Result of the test sees Table 3:
Table 3 accelerated test is investigated the result
Accelerated test result shows: this product is in 40 degree environment, and its pH value related substance, content all slightly change, and need to preserve in the cool.
Prescription of the present invention is formed the process screening and is obtained, and screening process is as follows:
1, dosage form determines
Intranasal administration can be avoided the first pass effect and the gastrointestinal degraded of liver, improves the bioavailability of chemicals and peptide medicament, and no pain during administration simultaneously is easy to be accepted by the patient.So we select the nasal mucosa administration, make nasal spray.
2, principal agent concentration determines
Between 15%～20%, and the blood drug level of Thymopentin can be brought into play its normal pharmacological action at 0.12～0.24ug/ml to nasal mucosa to the bioavailability (comparing with intravenous injection) of Thymopentin; Other has, we the design the micro-administration pump be 100ul/ time, when using at every turn about nasal cavity respectively be administered once.Given this, we determine that its principal agent concentration is 20mg/ml.
3, pH value determines
We get a little in 2～8 scopes by pH value, it is the most stable in 4.0～5.5 scopes to obtain the medicinal liquid pH value by 30 ℃ of accelerated tests, simultaneously the medicinal liquid pH value scope of its intranasal administration of stipulating with version pharmacopeia in 2005 is generally more approaching between 5.5～7.5, so we select 4.0～5.5 these scopes.
4, absorption enhancer and buffer system determines
Relevant bibliographical information mistake, citrate can promote the absorption of nasal mucosa to medicine; Citrate and phosphate can constitute the buffer system in 4.0～5.5 scopes simultaneously, so we select lemon hydrochlorate-phosphate buffer for use, its concentration is citric acid monohydrate chemical compound 1.36mg/ml, sodium hydrogen phosphate two hydrate 2.4mg/ml.Use high-efficient liquid phase chromatogram determining content, carry out the adjuvant blank assay simultaneously, principal agent and adjuvant are noiseless.
5, antibacterial determines
We are chosen in this bundle oronain relatively more commonly used in the medical solution as antibacterial, and fungistatic effect is preferably arranged when the concentration of 8mg/100ml.Use high-efficient liquid phase chromatogram determining content, carry out the adjuvant blank assay simultaneously, principal agent and adjuvant are noiseless.
6, osmotic pressure regulator determines
After the supplementary material of above-mentioned 1-5 screening gained added according to preparation technology; record its osmotic pressure and be lower than the total milliosmolarity concentration (280～320mOsmol/L) of blood plasma in the human body; then we add osmotic pressure regulator sodium chloride 0.6% (w/v) commonly used; its osmotic pressure concentration is remained in 280～320mOsmol/L scope, play the effect of protection nasal mucosa.Use high-efficient liquid phase chromatogram determining content, carry out the adjuvant blank assay simultaneously, principal agent and adjuvant are noiseless.
7, determine prescription
Thymopentin: 25.0g
Sodium chloride: 7.5g
Citric acid monohydrate chemical compound: 1.7g
Sodium hydrogen phosphate two hydrates: 3.0g
This bundle oronain (50%): 0.2g
Add the injection water extremely: 1250ml
PH transfers to 4.0～5.5 and makes 500 bottles altogether
Preparation of the present invention is a pharmaceutical solutions, and production process need be controlled product quality, and the present invention also provides the method for quality control of product of the present invention for this reason, comprises character, differentiates, checks that steps such as assay, concrete steps are seen embodiment 2.
Pharmaceutical preparation of the present invention, the selection of its good prescription composition and PH scope makes preparation stabilization of the present invention, and the storage time is long, can repeatedly use behind the uncap, and is easy to use, with low cost.
The specific embodiment:
Embodiment 1
It is as follows to write out a prescription:
Thymopentin: 25.0g
Sodium chloride: 7.5g
Citric acid monohydrate chemical compound: 1.7g
Sodium hydrogen phosphate two hydrates: 3.0g
This bundle oronain (50%): 0.2g
Add the injection water extremely: 1250ml
PH transfers to 4.0～5.5 and makes 500 bottles altogether
The preparation method of preparation of the present invention is as follows:
1, in 100,000 grades of clean areas, takes by weighing the above-mentioned supplementary material of recipe quantity to sterilization container;
2, be stirred well to dissolving fully behind an amount of water for injection of adding;
3, regulate pH value to 4.0 between 5.0 with the hydrochloric acid of 0.1M or sodium hydroxide;
4, adding to the full amount of water for injection;
5, be transferred in ten thousand grades of clean areas, through 0.22um microporous filter membrane fine straining; And measure content, pH value, medicinal liquid clarity etc.;
6, carry out fill after qualified, add pump, roll lid and add medicated cap;
7, examine entirely qualified after, labeling, the dress box.
Embodiment 2
Method of quality control
Pentapeptide nose spraying agent for thymus gland
Xiongxianwutai?Bipenwuji
Thymopentin?Nasal?Spray
This product is the aqueous solution of Thymopentin.Contain Thymopentin (C in peptide content
30H
49N
9O
9) should be 90.0～110.0% of labelled amount.
[character] this product is a colourless clear liquid.
[discriminating]
(1), get the about 1mg of this product, add water 1ml and make dissolving, (get copper sulfate 0.15g, tartarize potassium sodium 0.6g adds water 50ml, stirs to add 10% sodium hydroxide solution 30ml down, adds water 100ml, i.e.) 1ml, promptly apparent bluish violet to add biuret reagent.
(2), in the chromatogram that under the assay item, writes down, the retention time of test sample main peak should be consistent with the retention time of reference substance main peak.
[inspection]
PH value is got this product, measures (two appendix VI of Chinese Pharmacopoeia version in 2005 H) in accordance with the law, and pH value should be 4.0～5.5.
It is an amount of that related substance is got this product, adds mobile phase and make the solution that contains Thymopentin 1mg among the 1ml, as need testing solution; It is an amount of that precision is measured need testing solution, is diluted to the solution of 0.01mg among every 1ml, solution in contrast with mobile phase.According to the test of the chromatographic condition under the assay item, get contrast solution 100 μ l, inject chromatograph of liquid, regulate instrumental sensitivity, make main peak high, get need testing solution 100 μ l again for 10%～20% of full scale, inject chromatograph of liquid, the record chromatogram is to 2.5 times of the main peak retention time.If any impurity peaks, single maximum contaminant peak area should be crossed contrast solution main peak area (2.0%) in the need testing solution chromatogram, and each impurity peak area sum should be crossed 2.5 times (5.0%) of contrast solution main peak area.
Every bottle of total spray time is got 4 of this product, removes cap respectively, the precision (W that weighs
1); Wash shower nozzle after the examination spray 10 times, the precision (W that weighs after the intensive drying
2); Wash shower nozzle behind the continuous injection 10 times again, the dry back precision (W that weighs
3)); Atomizing pump is pried open, discarded medicinal liquid, wash after the mold-formed bottle drying precision (W that weighs
4), be calculated as follows every bottle of total spray time, all should be no less than every bottle and indicate total spray time.Always spray inferior=10 * (W
1-W
4) ÷ (W
2-W
3)
Every spray drug content is got 1 bottle of this product, remove cap, the examination spray washes shower nozzle for several times after being normal vaporific discharge rate, the small beaker of getting clean dried tiltedly is buckled on the nozzle, continuous injection 20 times, with mobile phase the medicinal liquid in the beaker quantitatively is transferred in the 10ml measuring bottle, and is diluted to scale, measure according to the method under the assay item, the gained result is every spray drug content divided by 20.Every spray drug content should be 80～120% of labelled amount.
Droplet distributes and gets this product, checks (Chinese Pharmacopoeia version appendix in 2005 X H) in accordance with the law, and the droplet medication amount should be no less than 15% of every spray drug content labelled amount.
Loading amount is got 5 of this product, and medicinal liquid is also taken out to the greatest extent through the syringe of markization in advance with dry respectively, reads the loading amount of every bottle liquid medicine, and asks its average loading amount, should be up to specification.
Microbial limit is got this product, checks (two appendix XI of Chinese Pharmacopoeia version in 2000 J membrane-filter procedure) in accordance with the law, should be up to specification.
[assay] measured according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia current edition D).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; 0.05mol/L phosphate buffer (pH7.0)-methanol (90: 10) is mobile phase; The detection wavelength is 275nm.Number of theoretical plate calculates by the Thymopentin peak should be not less than 1200.
Algoscopy is got 5 of this product, gets 1ml behind the mixing, adds the mobile phase dilution and makes the solution that contains Thymopentin 0.5mg among every 1ml approximately, and as need testing solution, precision is measured 20 μ l, injects chromatograph of liquid, the record chromatogram; In addition precision takes by weighing that to be dried to the Thymopentin reference substance of constant weight through phosphorus pentoxide an amount of, makes the solution that contains Thymopentin 0.5mg among every 1ml approximately with mobile phase dissolving and dilution, and solution is measured with method in contrast.Press external standard method with calculated by peak area, promptly.
[classification] immunomodulator
[specification] (1) 2.5ml:60mg (22 sprays, 2.4mg/ spray)
[storage] covers light, and shady and cool place preserves.
[effect duration] tentative 2 years
Claims (10)
1, a kind of Thymopentin intranasal administration preparation.
2, the described preparation of claim 1 is characterized in that, described preparation is a nasal spray, is made up of Thymopentin and suitable pharmaceutic adjuvant.
3, the described preparation of claim 2, it is characterized in that described pharmaceutic adjuvant is selected from osmotic pressure regulator, absorption enhancer, stabilizing agent, buffer agent, antiseptic and antioxidant.
4, the described preparation of claim 3, it is characterized in that wherein osmotic pressure regulator is selected from sodium chloride, glucose, glycerol, mannitol, sorbitol, sodium chloride, boric acid, glucose, Borax;
Absorption enhancer is selected from Fructus Citri Limoniae acids, salicylic acid, terpenoid, quintessence oil and lactone, as book lotus brain, Borneolum Syntheticum, Oleum Eucalypti and Rhizoma Chuanxiong, Elettaria cardamomum (L.) Maton;
Stabilizing agent is selected from 20 kinds of human amino acids such as glycine, low molecular dextran, ethylenediaminetetraacetic acid, disodiumedetate, sodium ethylene diamine tetracetate calcium;
Buffer agent is selected from phosphate, acetate, citrate, citric acid-sodium dihydrogen phosphate, citric acid-sodium hydrogen phosphate etc.;
Antiseptic is selected from benzyl alcohol, chlorobutanol, thimerosal, phenylmercuric nitrate, benzalkonium chloride, hibitane, phenoxyethanol, Nipagin ester, sorbic acid;
Antioxidant is selected from sodium sulfite, sodium metabisulfite, cysteine, paddy cystine, ascorbic acid.
5, the described preparation of claim 4, it is characterized in that prescription consists of: 0.1-100mg/ml Thymopentin, 5-100mM/L citric acid-sodium hydrogen phosphate, 0.001-0.5%w/v disodiumedetate, 0.05-1.0%w/v sodium sulfite, 0-9.0%w/v sodium chloride, 0.001-0.05%w/v benzalkonium chloride.
6, the described preparation of claim 5, it is characterized in that prescription consists of: 1-50mg/ml Thymopentin, 5-50mM/L citric acid-sodium hydrogen phosphate, 0.01-0.1%w/v disodiumedetate, 0.1-0.5%w/v sodium sulfite, 5.0-8.0%w/v sodium chloride, 0.01-0.03%w/v benzalkonium chloride.
7, the described preparation of claim 6, it is characterized in that prescription consists of: 20mg/ml Thymopentin, 15mM/L citric acid-sodium hydrogen phosphate, 0.05%w/v disodiumedetate, 0.2%w/v sodium sulfite, 6.0%w/v sodium chloride, 0.016%w/v benzalkonium chloride.
8, the preparation method of the pharmaceutical preparation of claim 1 is characterized in that, method is as follows:
1), in 100,000 grades of clean areas, takes by weighing the above-mentioned supplementary material of recipe quantity to sterilization container;
2), be stirred well to dissolving fully behind an amount of water for injection of adding;
3), regulate pH value to 4.0 between 5.0 with the hydrochloric acid of 0.1M or sodium hydroxide;
4), adding to the full amount of water for injection;
5), be transferred in ten thousand grades of clean areas, through 0.22um microporous filter membrane fine straining; And measure content, pH value, medicinal liquid clarity etc.;
6) carry out fill after, qualified, add pump, roll lid and add medicated cap;
7) examine, entirely qualified after, labeling, the dress box.
9, the method for quality control of the pharmaceutical preparation of claim 1 is characterized in that, comprises character is observed, and content is differentiated, content is checked, the effective ingredient that contains is carried out assay, wherein
[character] this product is a colourless clear liquid;
[discriminating] (1), get the about 1mg of this product, add water 1ml and make dissolving, add biuret reagent 1ml, promptly show bluish violet;
(2), in the chromatogram that under the assay item, writes down, the retention time of test sample main peak should be consistent with the retention time of reference substance main peak;
[inspection] pH value is got this product, measures according to two appendix VI of Chinese Pharmacopoeia version in 2005 H method, and pH value is 4.0～5.5;
It is an amount of that related substance is got this product, adds mobile phase and make the solution that contains Thymopentin 1mg among the 1ml, as need testing solution; It is an amount of that precision is measured need testing solution, is diluted to the solution of 0.01mg among every 1ml, solution in contrast with mobile phase; According to the test of the chromatographic condition under the assay item, get contrast solution 100 μ l, inject chromatograph of liquid, regulate instrumental sensitivity, make main peak high, get need testing solution 100 μ l again for 10%～20% of full scale, inject chromatograph of liquid, the record chromatogram is to 2.5 times of the main peak retention time.If any impurity peaks, single maximum contaminant peak area should be crossed contrast solution main peak area (2.0%) in the need testing solution chromatogram, and each impurity peak area sum should be crossed 2.5 times (5.0%) of contrast solution main peak area;
Every bottle of total spray time is got 4 of this product, removes cap respectively, the precision (W that weighs
1); Wash shower nozzle after the examination spray 10 times, the precision (W that weighs after the intensive drying
2); Wash shower nozzle behind the continuous injection 10 times again, the dry back precision (W that weighs
3)); Atomizing pump is pried open, discarded medicinal liquid, wash after the mold-formed bottle drying precision (W that weighs
4), be calculated as follows every bottle of total spray time, all should be no less than every bottle and indicate total spray time; Always spray inferior=10 * (W
1-W
4) ÷ (W
2-W
3);
Every spray drug content is got 1 bottle of this product, remove cap, the examination spray washes shower nozzle for several times after being normal vaporific discharge rate, the small beaker of getting clean dried tiltedly is buckled on the nozzle, continuous injection 20 times, with mobile phase the medicinal liquid in the beaker quantitatively is transferred in the 10ml measuring bottle, and is diluted to scale, measure according to the method under the assay item, the gained result is every spray drug content divided by 20.Every spray drug content should be 80～120% of labelled amount;
Droplet distributes and gets this product, checks that according to Chinese Pharmacopoeia version appendix in 2005 XH method the droplet medication amount should be no less than 15% of every spray drug content labelled amount;
Loading amount is got 5 of this product, and medicinal liquid is also taken out to the greatest extent through the syringe of markization in advance with dry respectively, reads the loading amount of every bottle liquid medicine, and asks its average loading amount, should be up to specification;
Microbial limit is got this product, checks according to two appendix XI of Chinese Pharmacopoeia version in 2000 J membrane-filter procedure, should be up to specification;
[assay] is according to two appendix V of Chinese Pharmacopoeia current edition D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; 0.05mol/L pH7.0 phosphate buffer: methanol=90: 10 is mobile phase; The detection wavelength is 275nm, and number of theoretical plate calculates by the Thymopentin peak should be not less than 1200;
Algoscopy is got 5 of this product, gets 1ml behind the mixing, adds the mobile phase dilution and makes the solution that contains Thymopentin 0.5mg among every 1ml approximately, and as need testing solution, precision is measured 20 μ l, injects chromatograph of liquid, the record chromatogram; In addition precision takes by weighing that to be dried to the Thymopentin reference substance of constant weight through phosphorus pentoxide an amount of, makes the solution that contains Thymopentin 0.5mg among every 1ml approximately with mobile phase dissolving and dilution, and solution is measured with method in contrast.Press external standard method with calculated by peak area, promptly.
10, the application of the pharmaceutical preparation of claim 1 in the medicine of diseases such as chronic hepatitis B patient, various constitutional or Secondary cases T cell defect disease more than 18 years old of preparation treatment, some autoimmune disease, disease that various cellular immune function is low, tumor.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100981394A CN101318011B (en) | 2007-04-17 | 2007-04-17 | Pentapeptide nose spraying agent for thymus gland, preparation method and application thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100981394A CN101318011B (en) | 2007-04-17 | 2007-04-17 | Pentapeptide nose spraying agent for thymus gland, preparation method and application thereof |
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| CN101318011A true CN101318011A (en) | 2008-12-10 |
| CN101318011B CN101318011B (en) | 2012-03-14 |
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|---|---|---|---|
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105012232A (en) * | 2015-08-14 | 2015-11-04 | 北京世桥生物制药有限公司 | Thymopentin injection and preparation method thereof |
| CN108676085A (en) * | 2018-07-03 | 2018-10-19 | 李霞 | A kind of preparation method and its pharmaceutical composition of thymalfasin |
| CN111686242A (en) * | 2020-07-28 | 2020-09-22 | 沈阳眼产业技术研究院有限公司 | Spray containing IL-18 and IL-2 and its application in improving immunity |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6153592A (en) * | 1992-11-09 | 2000-11-28 | Port Systems, Llc | Enhancing the bioavailability of proteolytically labile therapeutic agents |
| CN100337684C (en) * | 2005-05-11 | 2007-09-19 | 北京双鹭药业股份有限公司 | Thymic pentapeptide aqua prepn and its prepn process and application |
-
2007
- 2007-04-17 CN CN2007100981394A patent/CN101318011B/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105012232A (en) * | 2015-08-14 | 2015-11-04 | 北京世桥生物制药有限公司 | Thymopentin injection and preparation method thereof |
| CN108676085A (en) * | 2018-07-03 | 2018-10-19 | 李霞 | A kind of preparation method and its pharmaceutical composition of thymalfasin |
| CN108676085B (en) * | 2018-07-03 | 2019-09-24 | 北京六盛合医药科技有限公司 | A kind of preparation method and its pharmaceutical composition of thymalfasin |
| CN111686242A (en) * | 2020-07-28 | 2020-09-22 | 沈阳眼产业技术研究院有限公司 | Spray containing IL-18 and IL-2 and its application in improving immunity |
| CN111686242B (en) * | 2020-07-28 | 2023-08-01 | 沈阳眼产业技术研究院有限公司 | Spray containing IL-18 and IL-2 and its application in enhancing immunity |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101318011B (en) | 2012-03-14 |
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