CN101766603A - Intramuscular injection solution for enhancing immunity - Google Patents
Intramuscular injection solution for enhancing immunity Download PDFInfo
- Publication number
- CN101766603A CN101766603A CN200810240882A CN200810240882A CN101766603A CN 101766603 A CN101766603 A CN 101766603A CN 200810240882 A CN200810240882 A CN 200810240882A CN 200810240882 A CN200810240882 A CN 200810240882A CN 101766603 A CN101766603 A CN 101766603A
- Authority
- CN
- China
- Prior art keywords
- injection
- pidotimod
- salt
- arginine
- infection
- 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.)
- Pending
Links
Abstract
The invention discloses intramuscular injection solution for enhancing immunity. Pidotimod and sodium hydroxide or potassium hydroxide or arginine and the like are reacted in water or ethanol or mixed solution of water and ethanol so as to generate pidotimod sodium salt, potassium salt or arginine salt, and then the injection solution is prepared. The intramuscular injection solution is characterized in that: the pidotimod which is an active component in the injection solution exists in the form of the pidotimod sodium salt or the potassium salt or the arginine salt, and the pH value of the solution is within 4.0 to 6.0. The optimal range of the pidotimod or the pidotimod sodium salt or the potassium salt or the arginine salt in every 1ml injection is within 50 to 250mg. The preferential specification is 2ml: 0.2g or 3ml: 0.2g (according to the pidotimod). The injection solution is used for treating the following diseases: (1) repeated upper and lower respiratory tract infection (pharyngitis, trachitis, bronchitis and amygdalitis); (2) repeated infection of otorhinolaryngology (rhinitis, nasosinusitis and otitis); (3) infection of a urinary system; (4) infection of gynaecology; (5) clinical patients with poor cellular immune function after chemotherapy; (6) specific and non-specific immunodeficiency diseases such as cancer and the like. The injection solution is used for reducing the acute disease attacking number of times, shortening course of the disease and relieving the attacking degree. Moreover, the injection solution can also be used for adjuvant therapy of antibiotics when in acute infection.
Description
Technical field
The invention belongs to the medicine new technical field, relate to a kind of injection of administered intramuscular of enhancing immunity.1. this injection is used for the treatment of the last lower respiratory infection (pharyngitis, tracheitis, bronchitis, tonsillitis) of outbreak repeatedly; 2. department of otorhinolaryngology repeated infection (rhinitis, sinusitis, otitis); 3. urinary system infection; 4. gynecological infection; 5. the low clinical patients of cellular immune function after the chemotherapy; 6. specificity and nonspecific immunity defective disorders such as cancers etc.In order to reduce the number of times of acute attack, shorten the course of disease, alleviate the degree of outbreak; Antibiotic auxiliary treatment when also can be used as actute infection.A kind of preparation of injection of administered intramuscular of enhancing immunity and application thereof specifically.
Background technology
The immune system of human body is being defended the health of human body just as a well-trained crack troops.Immune system is people's usually said " immunity ", " resistance " to the defence capability of pathogen.
People's defence capability comprises nonspecific immunity and specific immunity.Nonspecific immunity is to be born with the man day, so be called the inherency immunity again, comprise the skin, mucosa of body barrier effect to pathogen, phagocyte in the blood, neutrophilic granulocyte be to the phagocytosis of pathogen, and complement, lyase bacterium, properdin, interferon etc. are to the killing action of pathogen.Specific immunity is meant human body to the resistance targetedly that certain pathogen had, and this immunity varies with each individual, and generally can obtain by prophylactic immunization, ill or inapparent infection.Specific immunity mainly forms after the people is born, so be acquired immunity again.
Sound immunity is to guarantee that body avoids the key factor of pathogen invasion and attack, and in fact, for some reason or other, often causes people's hypoimmunity.
Pidotimod (pidotimod) is a kind of brand-new chemosynthesis immunopotentiating agent, and its similar is in dipeptides.The later stage eighties 20th century is successfully synthesized by Italian Poli industria chimica S.P.A chemical company, and gets permission listing in 1993 and be used for clinical.
Pharmacodynamic study shows that pidotimod is an immunopotentiating agent, can promote nonspecific immune reaction, can promote specific immune response again.Pidotimod can promote the activate the phagocytic capacity of macrophage and neutrophilic granulocyte, improves its chemotaxis; Activate natural killer cell; The former lymphopoiesis that causes of mitosis promoting, the helper T lymphocyte (CD that reduces when making immunologic hypofunction
4 +) and suppressor T lymphocyte (CD
8 +) ratio raise to recover normal; By stimulating interleukin-2 and gamma interferon to promote cell immune response.
Although all showing pidotimod, animal experiment and clinical trial do not have directly antibiotic and antiviral activity, by bringing into play the curative effect that significant treatment antibacterial (Diplococcus pneumoniae, escherichia coli, bacillus pyocyaneus, Bacillus proteus etc.) and virus (influenza virus, herpes simplex virus, murine encephalomyocarditis virus and Mengo virus etc.) infect to the promotion of the immunologic function of human body.
Pidotimod is by cellular immunization, humoral immunization approach performance antibacterium, antiviral, the antifungic action of enhancing body.Clinical practice has all obtained good effect in repeatedly respiratory tract infection of control child, old people's chronic bronchitis, urinary system infection, malignant tumor and the chemotherapy of outbreak repeatedly, the auxiliary treatment after the radiotherapy.The multicenter open clinical trial shows that curative effect is reliable, and the human tolerance is good, and toxic and side effects is little.
Pidotimod was taken in the 31st edition Martin's pharmacopeia in 1996.Tianjin Jinshi Pharmaceutical Co., Ltd. has successfully developed the granule dosage form of pidotimod in 2000, and is four kind new medicines by state approval.Calendar year 2001, there has been pidotimod tablet (trade name " Wan Shining ") production in China's sun-stone (Tangshan) Pharma Inc., we can say that the imported product of pidotimod and production domesticization product have been on the same starting line.
The present invention is a kind of injection of administered intramuscular of enhancing immunity, effective active composition pidotimod in its injection is that the form with pidotimod sodium salt or potassium salt or arginine salt exists, so both increase the stability of pidotimod, also improved the water solublity of pidotimod simultaneously.The injection that contains pidotimod of the present invention, safety is good, good stability, the intramuscular injection good absorbing, the bioavailability height need not to add other adjuvant.
Summary of the invention
The injection of the administered intramuscular of a kind of enhancing immunity of the present invention is characterised in that the preparation method of the injection that is used for the administered intramuscular approach that contains pidotimod.Usually method for making is pidotimod is dissolved in or is suspended in the water, adds equimolar sodium hydroxide or potassium hydroxide or arginine then, at room temperature be stirred to dissolving fully after, be diluted to the concentration that needs.
The present invention also provides a kind of sodium salt that contains pidotimod or potassium salt or arginine salt to be prepared into the injection type of muscle administration, being equimolar pidotimod and sodium hydroxide to be reacted in water and the pidotimod sodium salt, potassium salt or the arginine salt aqueous solution that directly form, also can be it is the soluble in water and aqueous solution that forms behind the sodium salt that obtains pidotimod or potassium salt or arginine salt.Do not separating out solid by the injection that contains pidotimod sodium salt or potassium salt or arginine salt of the present invention during in long term store, and composition is still stable.
The preparation process of the injection of the administered intramuscular of a kind of enhancing immunity provided by the invention includes but not limited to following several:
(1) getting the pidotimod of equimolar amounts and sodium hydroxide or potassium hydroxide or arginine joins in an amount of water for injection, stirring makes dissolving fully, add an amount of pin charcoal, and continue to stir 20 minutes or 60 ℃ of insulations 20 minutes, filter decarburization, add water for injection to needed amount, the fine straining degerming, packing in 121 ℃ of sterilizations down, is made injection.
(2) get the pidotimod of equimolar amounts and sodium hydroxide or potassium hydroxide or arginine and join in an amount of ethanol, stir and make dissolving fully, filter.The concentrating under reduced pressure after drying is flung to ethanol and is promptly got powdered pidotimod sodium salt, potassium salt or arginine salt.Join again in an amount of water for injection, add or do not add acceptable accessories such as mannitol, dextran series, sorbitol, sodium chloride, glucose etc., add an amount of pin charcoal, and continue to stir 20 minutes or 60 ℃ of insulations 20 minutes, filter decarburization, add water for injection to needed amount, the fine straining degerming, packing in 121 ℃ of sterilizations down, is made injection; Or packing after the fine straining degerming, put in the freeze dryer after the lyophilization, make injection powder pin.
(3) get the pidotimod of equimolar amounts and sodium hydroxide or potassium hydroxide or arginine and join in an amount of ethanol, stir and make dissolving fully, filter.The concentrating under reduced pressure after drying is flung to ethanol and is promptly got powdered pidotimod sodium salt, potassium salt or arginine salt.Aseptic subpackaged in cillin bottle, promptly get injection powder pin.
Injection of the present invention is preferably in the scope of pH4.5～5.5 in pH4～9.The powder pin adds pH4～6 of its solution behind an amount of water for injection.
Advantage of the present invention is:
1, pidotimod sodium salt of Xing Chenging or potassium salt or the dissolubility of arginine salt in water are big and improved the stability of pidotimod.
2, pidotimod sodium salt of Xing Chenging or potassium salt or arginine salt make injection the time, adopt 121 ℃ of sterilizations of high temperature.Reached aseptic assurance level more.Safety is higher.
The specific embodiment
Following examples are to be used for illustrating the present invention, but do not limit the present invention in any way.
Embodiment 1: injection (specification 2ml:0.1g)
Getting 244.26g pidotimod and 40.01g sodium hydroxide joins in the 3500ml water for injection, stirring makes dissolving fully, add 4g pin charcoal, and continue to stir 20 minutes, filter decarburization, add water for injection to 4485.2ml, the fine straining degerming, packing, 2ml/ props up, in 121 ℃ of 20min that sterilize down, make injection.
Embodiment 2: injection (specification 2ml:0.2g)
Getting 244.26g pidotimod and 40.01g sodium hydroxide joins in the 2000ml water for injection, stirring makes dissolving fully, add 4g pin charcoal, 60 ℃ were stirred 20 minutes, filtered decarburization, add water for injection to 2442.6ml, the fine straining degerming, packing, 2ml/ props up, in 121 ℃ of 20min that sterilize down, make injection.
Embodiment 3: injection (specification 3ml:0.2g)
Get 244.26g pidotimod and 40.01g sodium hydroxide and join in the 2000ml ethanol, stir and make dissolving fully, filter, concentrating under reduced pressure reclaims ethanol, volatilizes, and gets pressed powder, is pidotimod sodium.
Above-mentioned pidotimod sodium is joined in the 3000ml water for injection, stir and make dissolving fully, add 4g pin charcoal, stirred 20 minutes, filter decarburization, add water for injection to 3660ml, fine straining degerming, packing, 3ml/ props up, and in 121 ℃ of 20min that sterilize down, makes injection.
Embodiment 4: injection (specification 2ml:0.2g)
Getting 244.26g pidotimod and 174.2g arginine joins in the 2000ml water for injection, stirring makes dissolving fully, add 4g pin charcoal, 60 ℃ were stirred 20 minutes, filtered decarburization, add water for injection to 2442.6ml, the fine straining degerming, packing, 2ml/ props up, in 121 ℃ of 20min that sterilize down, make injection.
Embodiment 5: injection powder pin (specification 0.2g)
Get 244.26g pidotimod and 40.01g sodium hydroxide and join in the 2000ml ethanol, stir and make dissolving fully, add 3g pin charcoal, stir 20min, filter decarburization, fine straining, concentrating under reduced pressure reclaims ethanol, volatilize under the aseptic condition, get pressed powder, be pidotimod sodium.
Direct packaging is in cillin bottle under aseptic condition with pidotimod sodium, and every bottled amount is counted 0.2g by pidotimod.Promptly.
Embodiment 6: injection powder pin (specification 0.2g)
Getting 244.26g pidotimod and 40.01g sodium hydroxide joins in the 4000ml water for injection, stirring makes dissolving fully, adds 200g mannitol and 4g pin charcoal, and 60 ℃ were stirred 20 minutes, filter decarburization, add water for injection to 4485ml, the fine straining degerming is counted the 0.2g fill by every bottle in cillin bottle with pidotimod, half tamponade, pre-freeze is 3 hours under-40 ℃ of conditions, is warming up to 30 ℃ by 3～5 ℃/hour then, is incubated dehydration in 3 hours.The lock aluminium lid is taken out in tamponade.Promptly.
Sample preparation:
Prescription:
Supplementary material title inventory
Pidotimod 244.26g
Sodium hydroxide 40.01g
Active carbon 4g
Water for injection adds to 2442.6ml
?????????????????????????????????????
Make 1221
Operating procedure: pidotimod and the sodium hydroxide of getting recipe quantity join (water temperature should be lower than 30 ℃) in the 2000ml water for injection, stirring makes dissolving fully, add 4g pin charcoal, 60 ℃ were stirred 20 minutes, filtered decarburization, add water for injection to 2442.6ml, the fine straining degerming, packing, 2ml/ props up, in 121 ℃ of 20min that sterilize down, make injection.
Safety testing:
Get stimulation and the hypersensitive test of the 080303 batch of product of pidotimod injection, prove that this product do not have the anaphylaxis of haemolysis, no muscular irritation, blood vessel irritation and muscle administration through the muscle administration.Can use for the muscle administration.
Stability test:
Investigate sample
Test sample: pidotimod injection
Source: Beijing HuPoGuangHua Medical Sci-Tech Development Co., Ltd
Lot number: 080301,080302,080303
Dosage form: injection
Specification: 2ml:0.2g
The investigation condition
| The investigation condition | Sample time | The test Packing Condition |
| Accelerated test (40 ℃ ± 2 ℃, RH75% ± 5%) | 0,1,2,3,6 month | Intend the listing packing |
| Long term test (25 ℃ ± 2 ℃, RH60% ± 10%) | 0,3,6,9,12,18,24,36 month | Intend the listing packing |
Investigate the result
Three batches of preproduction accelerated tests are investigated the result
Three batches of preproduction long term tests are investigated the result
Investigate the result from the accelerated test and the long term test of three batches of preproductions, formulation and technology is reasonable, sample is stable, meets big production requirement.Above-mentioned sample is also among continuation is investigated.
Claims (9)
1. the injection of the administered intramuscular of an enhancing immunity is characterized in that the active component that contains in the injection is various salt types such as pidotimod or its sodium salt, potassium salt, arginine salt.
2. the injection of the administered intramuscular of a kind of enhancing immunity according to claim 1 is characterized in that active component pidotimod in this injection is that form with pidotimod sodium salt, potassium salt, arginine salt exists.
3. the injection of the administered intramuscular of a kind of enhancing immunity according to claim 1 is characterized in that it is to be used for administered intramuscular.
4. the injection of the administered intramuscular of a kind of enhancing immunity according to claim 3, the pH value that it is characterized in that the solution of this injection is 4.0～6.0, optimal pH is 4.5～5.5.
5. the injection of the administered intramuscular of a kind of enhancing immunity according to claim 3 is characterized in that pidotimod that the every 1ml of this injection contains or sodium salt, potassium salt, arginine salt are 20mg～500mg.
6. the injection of the administered intramuscular of a kind of enhancing immunity according to claim 5 is characterized in that the pidotimod that contains among the every 1ml of this injection or pidotimod sodium salt or potassium salt or arginine salt optimum range are 50mg～250mg.Preferred specification is 2ml:0.2g or 3ml:0.2g (in pidotimod).
7. the injection of the administered intramuscular of a kind of enhancing immunity according to claim 2 is characterized in that pidotimod sodium salt, potassium salt, arginine salt are to be added by pidotimod to make after equimolar sodium hydroxide or potassium hydroxide or arginine react in The suitable solvent (water or ethanol or the mixed liquor of the two).
8. the injection of the administered intramuscular of a kind of enhancing immunity according to claim 2 is characterized in that the preparation process of injection includes but not limited to following several:
(1) getting the pidotimod of equimolar amounts and sodium hydroxide or potassium hydroxide or arginine joins in an amount of water for injection, stirring makes dissolving fully, add an amount of pin charcoal, and continue to stir 20 minutes or 60 ℃ of insulations 20 minutes, filter decarburization, add water for injection to needed amount, the fine straining degerming, packing in 121 ℃ of sterilizations down, is made injection.
(2) get the pidotimod of equimolar amounts and sodium hydroxide or potassium hydroxide or arginine and join in an amount of ethanol, stir and make dissolving fully, filter.The concentrating under reduced pressure after drying is flung to ethanol and is promptly got powdered pidotimod sodium salt or potassium salt or arginine salt.Join again in an amount of water for injection, add or do not add acceptable accessories such as mannitol, dextran series, sorbitol, sodium chloride, glucose etc., add an amount of pin charcoal, and continue to stir 20 minutes or 60 ℃ of insulations 20 minutes, filter decarburization, add water for injection to needed amount, the fine straining degerming, packing in 121 ℃ of sterilizations down, is made injection; Or packing after the fine straining degerming, put in the freeze dryer after the lyophilization, make injection powder pin.
(3) get the pidotimod of equimolar amounts and sodium hydroxide or potassium hydroxide or arginine and join in an amount of ethanol, stir and make dissolving fully, filter.The concentrating under reduced pressure after drying is flung to ethanol and is promptly got powdered pidotimod sodium salt or potassium salt or arginine salt.Aseptic subpackaged in cillin bottle, promptly get injection powder pin.
9. the injection of the administered intramuscular of a kind of enhancing immunity according to claim 1 is characterized in that 1. this injection is used for the treatment of the last lower respiratory infection (pharyngitis, tracheitis, bronchitis, tonsillitis) of outbreak repeatedly; 2. department of otorhinolaryngology repeated infection (rhinitis, sinusitis, otitis); 3. urinary system infection; 4. gynecological infection; 5. the low clinical patients of cellular immune function after the chemotherapy; 6. specificity and nonspecific immunity defective disorders such as cancers etc.In order to reduce the number of times of acute attack, shorten the course of disease, alleviate the degree of outbreak; Antibiotic auxiliary treatment when also can be used as actute infection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810240882A CN101766603A (en) | 2008-12-26 | 2008-12-26 | Intramuscular injection solution for enhancing immunity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810240882A CN101766603A (en) | 2008-12-26 | 2008-12-26 | Intramuscular injection solution for enhancing immunity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101766603A true CN101766603A (en) | 2010-07-07 |
Family
ID=42499804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810240882A Pending CN101766603A (en) | 2008-12-26 | 2008-12-26 | Intramuscular injection solution for enhancing immunity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101766603A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102492020A (en) * | 2011-11-28 | 2012-06-13 | 海南灵康制药有限公司 | Pidotimod compound and new preparation method thereof |
| CN102525902A (en) * | 2012-01-20 | 2012-07-04 | 江苏吴中医药集团有限公司 | High concentration pidotimod oral liquid |
| WO2016113242A1 (en) * | 2015-01-15 | 2016-07-21 | Polichem S.A. | Di-pidotimod benzathine and solid forms thereof |
| CN112898291A (en) * | 2021-01-27 | 2021-06-04 | 北京金城泰尔制药有限公司沧州分公司 | Preparation method of pidotimod sodium |
-
2008
- 2008-12-26 CN CN200810240882A patent/CN101766603A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102492020A (en) * | 2011-11-28 | 2012-06-13 | 海南灵康制药有限公司 | Pidotimod compound and new preparation method thereof |
| CN102492020B (en) * | 2011-11-28 | 2013-03-20 | 海南灵康制药有限公司 | Pidotimod compound and new preparation method thereof |
| CN102525902A (en) * | 2012-01-20 | 2012-07-04 | 江苏吴中医药集团有限公司 | High concentration pidotimod oral liquid |
| CN102525902B (en) * | 2012-01-20 | 2013-07-10 | 江苏吴中医药集团有限公司 | High concentration pidotimod oral liquid |
| WO2016113242A1 (en) * | 2015-01-15 | 2016-07-21 | Polichem S.A. | Di-pidotimod benzathine and solid forms thereof |
| WO2016112977A1 (en) | 2015-01-15 | 2016-07-21 | Polichem S.A. | Di-pidotimod benzathine and solid forms thereof |
| CN112898291A (en) * | 2021-01-27 | 2021-06-04 | 北京金城泰尔制药有限公司沧州分公司 | Preparation method of pidotimod sodium |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW576743B (en) | Extended release formulations of erythromycin derivatives | |
| EP0114589B1 (en) | Inhibition of angiogenesis | |
| US4006224A (en) | Method and agent for treating inflammatory disorders of the gastrointestinal tract | |
| JPH02290814A (en) | Psoralen reagent composition | |
| US5006551A (en) | Composition for destroying malignant tumors | |
| JP2020526583A5 (en) | ||
| WO2015058664A1 (en) | Use of icariin in preparing medicine for preventing or treating decrease in blood cells | |
| EA029649B1 (en) | Pomegranate-peel polyphenol gel used to treat gynecological inflammation diseases and method for preparation thereof | |
| CN101766603A (en) | Intramuscular injection solution for enhancing immunity | |
| PT1684770E (en) | Oligo-beta-(1,3)-glucan and monoclonal antibodies against cancer | |
| US6720011B1 (en) | Injectable composition for cancer treatment | |
| Baggot et al. | Pharmacokinetic interpretation of erythromycin and tylosin activity in serum after intravenous administration of a single dose to cows | |
| EP2338495A1 (en) | Iron bis-glycinate chelate for use in the oral treatment of anemia in patients with celiac disease | |
| CN101411684A (en) | Injection containing pidotimod sodium salt | |
| CN101423516A (en) | Preparation of pidotimod sodium and medicinal use thereof | |
| US6726913B1 (en) | Treatment of dermal tumors, warts, and viral infections of the respiratory tract in humans using heat-killed P. acnes | |
| US20100239646A1 (en) | Sublingual methotrexate and methotrexate patches | |
| CN101768156A (en) | Pidotimod arginine salt and preparation thereof | |
| JPS6115840A (en) | Immuno-activating agent | |
| WO2001054727A1 (en) | Treatment of dermal tumors, warts, and viral infections using heat-killed p. acnes | |
| CN101422428A (en) | Injection containing sodium pidotimod | |
| KR102374820B1 (en) | Pharmaceutical composition for the treatment of neuropathic pain comprising pregabalin and tianeptine | |
| JPH0563452B2 (en) | ||
| JP2004010605A (en) | Antitumor agent given by using mixture of deacetylated and deoxygenated mushrooms, fermented ganoderma spawn, and other mixture, and health food product, and feed additive containing the agent | |
| CN101455665A (en) | Preparation method of pidotimod dispersible table and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20100707 |