CN102327229B - A kind of Pidotimod dry suspension - Google Patents
A kind of Pidotimod dry suspension Download PDFInfo
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- CN102327229B CN102327229B CN201110290215.8A CN201110290215A CN102327229B CN 102327229 B CN102327229 B CN 102327229B CN 201110290215 A CN201110290215 A CN 201110290215A CN 102327229 B CN102327229 B CN 102327229B
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Abstract
The present invention provides a kind of Pidotimod dry suspension, is made up of pidotimod and adjuvant, and described adjuvant is filler, suspending agent and correctives, it is characterised in that described correctives is the mixture of strawberry essence, trisodium citrate, sodium chloride and aspartame。The present invention, by selecting specific correctives, is possible not only to solve well the sensory issues of Pidotimod dry suspension, and surprisingly, it was found that also have rapid-action, contributes to the effect of the stability of Pidotimod dry suspension。
Description
Technical field
The present invention provides a kind of pidotimod preparation, specifically, relates to a kind of Pidotimod dry suspension。Belong to field of pharmaceutical preparations。
Background technology
Pidotimod (pidotimod) is a kind of brand-new chemosynthesis immunopotentiating agent, and it is similar to that dipeptides。Suitable in the low disease of cellular immune function, the immunity such as human respiratory can be significantly improved。Pidotimod works by stimulating and regulate cell-mediated immunoreation, is widely used in the respiratory tract infection of the low recurrent exerbation of cellular immune function, ear, nose, larynx infection and urinary system infection, gynecological infection。The number of times of acute attack can be reduced, shorten the course of disease, alleviate the degree of outbreak, be alternatively arranged as antibiotic auxiliary treatment during actute infection。
Oral and intramuscular injection has good bioavailability, can promote nonspecific immune reaction, can promote again specific immune response。Pidotimod can promote the phagocytic activity of macrophage and neutrophilic granulocyte, improves its chemotaxis；Activate natural killer cell；The former lymphopoiesis caused of mitosis promoting, makes the helper T lymphocyte (CD reduced during immunologic hypofunction4 +) and suppressor T lymphocyte (CD8 +) ratio raise or recover normal；By stimulating interleukin-2 and gamma interferon to promote cell immune response。
Animal experiment and clinical trial all show, although pidotimod is without directly antibacterial and antiviral activity, but treat antibacterial (Diplococcus pneumoniae, escherichia coli, bacillus pyocyaneus, Bacillus proteus etc.) significantly and curative effect that virus (influenza virus, herpes simplex virus, murine encephalomyocarditis virus and Mengo virus etc.) infects by the promotion of body's immunity can be played。Pidotimod is heterogeneous broad immune accelerator, effectively can react by too many levels enhancing body anti-infectious immunity, significantly improve every immune indexes of immune level immunocompromised patients；Cannot be only used for treatment antibacterial to infect, it is also possible to be used for treating viral infection；It is applied not only to prevention infect, it is also possible in the control of actute infection outbreak, it is often more important that treat intractable repeated infection evident in efficacy；Topmost immunodeficiency-T cell subgroup is unbalance and functions of neutrophils reduces can also effectively to correct infant, recovers and strengthens its ability removing virus and pathogenic bacterium, reduce the number of times of infection and recurrence；Pidotimod safety is good, easy to use, rapid-action, is a kind of immunomodulating accelerator having good prospect。
Summary of the invention
For overcoming the single defect being unfavorable for clinical practice of pidotimod preparation in prior art, the present invention designs and provides a kind of Pidotimod dry suspension。
Dry suspension mainly needs suspended particles to have suitable dispersion, and should be uniformly dispersed as far as possible, to reduce the sedimentation velocity of microgranule, makes suspensoid be in steady statue。Next also needs to product good mouthfeel。And, the mouthfeel of pidotimod is poor, and solving its oral compliance is also technical barrier。
It is a discovery of the invention that by selecting specific correctives, be possible not only to solve well the sensory issues of Pidotimod dry suspension, and surprisingly, it was found that also have rapid-action, contribute to the effect of the stability of Pidotimod dry suspension。
Technical solution of the present invention is as follows:
The present invention provides a kind of Pidotimod dry suspension, is made up of pidotimod and adjuvant, and described adjuvant is filler, suspending agent and correctives, it is characterised in that described correctives is the mixture of strawberry essence, trisodium citrate, sodium chloride and aspartame。
Wherein, the weight ratio of Pidotimod dry suspension described above, it is characterised in that in described correctives, trisodium citrate and sodium chloride is 1: 1～20: 1, it is preferred to 10: 1。
Wherein, the weight ratio of Pidotimod dry suspension described above, it is characterised in that in described correctives, aspartame and strawberry essence is 1: 1～20: 1, it is preferred to 10: 1。
Wherein, the weight ratio of Pidotimod dry suspension described above, it is characterised in that in described correctives, trisodium citrate and aspartame is 5: 1～50: 1, it is preferred to 25: 1。
Preferably, the Pidotimod dry suspension that the present invention is described above, it is characterised in that in described correctives, trisodium citrate: sodium chloride: aspartame: the weight ratio of strawberry essence is preferably 250: 25: 10: 1。
Wherein, Pidotimod dry suspension described above, it is characterized in that wherein said filler in sucrose, lactose, mannitol, starch, xylitol, maltose alcohol, the starch milk saccharide complex one or more, it is preferred to the mixture of sucrose and mannitol。
Wherein, Pidotimod dry suspension described above, it is characterised in that wherein said suspending agent in carbomer, tragakanta, sodium carboxymethyl cellulose, the sodium alginate one or more, it is preferred to carbomer。
As the embodiment of the invention, it is provided that a kind of Pidotimod dry suspension, it is made 1000 bags by following component:
Wherein, Pidotimod dry suspension described above, it is characterised in that be make by the following method: pidotimod, sucrose, mannitol, trisodium citrate, sodium chloride are crossed respectively 80 mesh sieves, weigh by recipe quantity, mix homogeneously, adds 50% ethanol soft material, and 25 mesh sieves are granulated, 60 DEG C dry (moisture < 1.0%), 30 mesh sieve granulate, add carbomer, strawberry essence, aspartame, mix homogeneously, intermediate is subpackage after every quality inspection is qualified, to obtain final product。
Because pidotimod mouthfeel is uncomfortable, for convenience of patient medication, improve compliance thus correctives need to be added this product is carried out taste masking。By the multiple correctivess such as aspartame, cyclamate, strawberry essence, apple essence, trisodium citrate, sodium chloride are screened, found that, better using the mixed-powder of aspartame, strawberry essence, trisodium citrate and sodium chloride as correctives, the Pidotimod dry suspension not only prepared has good taste, also contributes to the stability of preparation。
In the Pidotimod dry suspension of the present invention, diluent is not particularly limited, it is possible to for the test of the multiple auxiliary materials such as sucrose, lactose, mannitol, starch, wherein, more preferably using sucrose and mannitol as diluent, this product also can be made to possess good mouthfeel。
In the Pidotimod dry suspension of the present invention, suspending agent can select carbomer, tragakanta, sodium carboxymethyl cellulose, sodium alginate etc., but more preferably uses carbomer as the suspending agent of Pidotimod dry suspension。According to embodiment 1 prescription and preparation technology, different suspending agents, the suspending effect of obtained Pidotimod dry suspension all can reach the requirement of dry suspension, but carbomer is compared with other suspending agent suspending better effects if (see table 1)。
Table 1 suspending agent result of the test (sedimentation volume ratio)
Accompanying drawing explanation
Mean blood plasma concentration-time graph the comparison diagram of pidotimod after Figure 120 name experimenter's oral test preparation and reference preparation
Detailed description of the invention
Embodiment 1: Pidotimod dry suspension
One. prescription
Two. preparation technology
Pidotimod, sucrose, mannitol, trisodium citrate, sodium chloride are crossed respectively 80 mesh sieves, weigh by recipe quantity, mix homogeneously, adds 50% ethanol soft material, and 25 mesh sieves are granulated, 60 DEG C dry (moisture < 1.0%), 30 mesh sieve granulate, add carbomer, strawberry essence, aspartame, mix homogeneously, intermediate is subpackage after every quality inspection is qualified, to obtain final product。
Comparative example 1:
(1) according to embodiment 1 prescription composition and technique, inventory is 50 bags, respectively strawberry essence is replaced with apple essence (comparative example 1A), flavoring banana essence (comparative example 1B), flavoring orange essence (comparative example 1C), milk flavour (1D), in prescription, all the other components are identical with consumption。
(2) according to embodiment 1 prescription composition and technique, inventory is 50 bags, and wherein without strawberry essence (comparative example 1E), in prescription, all the other components are identical with consumption。
(3) according to embodiment 1 prescription composition and technique, wherein inventory is 50 bags, wherein not sodium chloride-containing (comparative example 1F), and in prescription, all the other components are identical with consumption。
(4) according to embodiment 1 prescription composition and technique, wherein inventory is 50 bags, and wherein without aspartame (comparative example 1G), in prescription, all the other components are identical with consumption。
(5) according to embodiment 1 prescription composition and technique, wherein inventory is 50 bags, and wherein without carbomer (comparative example 1H), in prescription, all the other components are identical with consumption。
(6) according to embodiment 1 prescription composition and technique, inventory is 50 bags, and trisodium citrate is replaced sodium bicarbonate (comparative example 1I), and in prescription, all the other components are identical with consumption。
(7) according to embodiment 1 prescription composition and technique, inventory is 50 bags, aspartame replaces with all the other components in cyclamate (comparative example 1J) prescription identical with consumption。
Above comparative test result such as table 2 below。
Table 2 comparative test result
| Prescription is numbered | Mobility | Sedimentation volume ratio | Face shaping | Mouthfeel | Dissolution % | There is related substance % |
| Embodiment 1 | Good | 0.99 | White particle | Sour-sweet, mouthfeel is good | 99.3 | 0.45 |
| Comparative example 1A | Good | 0.98 | White particle | Sour-sweet, mouthfeel is general | 98.6 | 0.87 |
| Comparative example 1B | Good | 0.98 | White particle | Sour-sweet, mouthfeel is general | 96.8 | 0.92 |
| Comparative example 1C | Good | 0.97 | White particle | Sour-sweet, mouthfeel is general | 100.2 | 0.68 |
| Comparative example 1D | Good | 0.99 | White particle | Sour-sweet, mouthfeel is general | 97.7 | 1.23 |
| Comparative example 1E | Good | 0.99 | White particle | Sour-sweet, mouthfeel is poor | 98.4 | 0.52 |
| Comparative example 1F | Generally | 0.92 | White particle | Sour-sweet, mouthfeel is general | 98.9 | 0.66 |
| Comparative example 1G | Good | 0.98 | White particle | Acid, mouthfeel is very poor | 97.5 | 0.70 |
| Comparative example 1H | Generally | 0.86 | White particle | Sour-sweet, mouthfeel is poor | 98.2 | 0.69 |
| Comparative example 1I | Generally | 0.78 | Off-white color granule | Sour-sweet, puckery | 95.3 | 0.83 |
| Comparative example 1J | Good | 0.98 | White particle | Sour-sweet, mouthfeel is general | 98.0 | 0.73 |
The Pidotimod dry suspension of the present invention, by selecting specific adjuvant and proportioning, obtained Pidotimod dry suspension not only has good sedimentation volume ratio, mobility, dispersibility and mouthfeel and dissolution, and obtained Pidotimod dry suspension also has good stability。And technique is simple, and cost of supplementary product is cheap to be easy to get, it is easy to industrialized production。
Influence factor's test and result thereof: the Pidotimod dry suspension sample that Example 1 prepares carries out factors influencing test, place 10 days under high temperature (60 DEG C), high humidity (RH92.5%), high light (4500Lx) condition, respectively at 5,10 days last sampling and measuring。
Result is shown in table 3 below。
Table 3 influence factor's experiment investigation result
Result of the test shows, the Pidotimod dry suspension obtained by the present invention is all stable to high temperature, high humidity, high light, and indices is without obvious change。
Accelerated stability test and result thereof: the Pidotimod dry suspension sample that Example 1 prepares is accelerated study on the stability test, in 40 DEG C, the container of RH75% is placed, be measured respectively at 1,2,3,6 samplings at the end of month。
Result is in Table 4。
Table 4 accelerated test result
Long-term stable experiment and result thereof: the Pidotimod dry suspension sample that Example 1 prepares carries out long-time stability and investigates test, 25 DEG C, RH60% when, be measured respectively at 3,6,9,12,18,24 samplings at the end of month。
Result is in Table 5。
Table 5 long-term test results
Accelerated test and long-term stable experiment are it is shown that the Pidotimod dry suspension indices obtained by the present invention is without obvious change, and invention formulation meets good stability。
The test of pesticide effectiveness that the present invention produces
Bioequivalence is tested:
Experimenter's basic condition: 20 young male healthy volunteers are randomly divided into 2 groups, often group 10。Any medicine is not taken in test the last fortnight。Tested period unifies light diet。
Trial drug:
By test preparation (T): Pidotimod dry suspension, specification: 400mg/ bag, prepare according to embodiment 1。
Reference preparation (R): pidotimod sheet (trade name: pidotimod), specification: 400mg/ sheet, lot number: 080203, Taiyangshi (Tangshan) Pharm Ind Co., Ltd. produces。
Method of testing: adopting the method for designing of random packet, binary cycle dual crossing test, experimenter's overnight fasting is after at least 10 hours, by 2 bags of (400mg/ bag) Pidotimod dry suspensions with 250ml warm water delivery service。(total drug dose 800mg), takes medicine latter 2 hours and can drink water, within 4 hours, enter unified light diet。The 5ml (lucifuge) that respectively takes a blood sample for 0.13,0.25,0.50,0.75,1.0,1.5,2.0,2.5,3.0,4.0,6.0,9.0,12.0 hours before administration and after administration, with anticoagulant heparin, centrifugal 15 minutes of 3500rmp, separated plasma is also stored in-40 DEG C of refrigerators to be measured。Intersect by above-mentioned same program after one week and take medicine and take a blood sample。
Result is shown in Fig. 1。
Result of the test: clearly visible from Fig. 1, the Pidotimod dry suspension (T) of the present invention is after the tablet has been ingested in 0.5 hour, the blood drug level of human body is higher than pidotimod sheet (R), illustrates that the chewable tablet of the present invention easily absorbs, and has rapid-action feature。
Claims (2)
1. a Pidotimod dry suspension, is made up of pidotimod and adjuvant, it is characterised in that made 1000 bags by following component:
Wherein, the mixture of strawberry essence, trisodium citrate, sodium chloride and aspartame is correctives。
2. Pidotimod dry suspension according to claim 1, it is characterized in that making by the following method: pidotimod, sucrose, mannitol, trisodium citrate, sodium chloride are crossed 80 mesh sieves respectively, weighs by recipe quantity, mix homogeneously, add 50% ethanol soft material, 25 mesh sieves are granulated, and 60 DEG C are dried to moisture < 1.0%, 30 mesh sieve granulate, add carbomer, strawberry essence, aspartame, mix homogeneously, intermediate is subpackage after every quality inspection is qualified, to obtain final product。
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| CN109106687A (en) * | 2018-09-14 | 2019-01-01 | 广州大光制药有限公司 | A kind of Pidotimod dry suspension and preparation method thereof |
Citations (2)
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| CN1526390A (en) * | 2003-03-03 | 2004-09-08 | 浙江仙琚制药股份有限公司 | Piduomode granule and its prepn |
| CN1813685A (en) * | 2005-12-09 | 2006-08-09 | 韩志强 | Couted particle for reinforcing pidotimod acid-base stability, and its production method and use |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1526390A (en) * | 2003-03-03 | 2004-09-08 | 浙江仙琚制药股份有限公司 | Piduomode granule and its prepn |
| CN1813685A (en) * | 2005-12-09 | 2006-08-09 | 韩志强 | Couted particle for reinforcing pidotimod acid-base stability, and its production method and use |
Non-Patent Citations (2)
| Title |
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| 董海军.匹多莫德干混悬剂人体药动学及生物等效性研究.《中国药房》.2008,第19卷(第35期),第2750-2752页. * |
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