CN102552916A - New use of sodium salicylate - Google Patents
New use of sodium salicylate Download PDFInfo
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- CN102552916A CN102552916A CN2010105811781A CN201010581178A CN102552916A CN 102552916 A CN102552916 A CN 102552916A CN 2010105811781 A CN2010105811781 A CN 2010105811781A CN 201010581178 A CN201010581178 A CN 201010581178A CN 102552916 A CN102552916 A CN 102552916A
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- external preparation
- sodium salicylate
- recombined streptokinase
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Abstract
The invention discloses a new use of sodium salicylate as a penetration enhancer in an external preparation. The external preparation treats a recombined streptokinase as a main drug effect component and is used for treating hemorrhoidal diseases. The invention further discloses the external preparation for treating the hemorrhoidal diseases. The main drug component is the recombined streptokinase with the concentration of 80,000-180,000IU/g, and the external preparation also contains 0.01-3wt% of sodium salicylate as the penetration enhancer. A recombined streptokinase ointment prepared by adopting sodium salicylate as the penetration enhancer has a good transdermal effect, and the prepared external preparation can be used to treat the hemorrhoidal diseases.
Description
Technical field
The present invention relates to biotechnology and field of medical applications, be specifically related to purposes and the related application of sodium salicylate as penetrating agent in the recombined streptokinase external preparation.
Background technology
Sodium salicylate is as a kind of antipyretic-antalgic commonly used and non_steroidal anti_inflammatory drug, and its mechanism of action is similar with aspirin, through suppressing cyclooxygenase, reduces the synthetic of prostaglandin, plays antiinflammatory, rheumatism and antipyretic effect.Its antiinflammatory anti rheumatism action is similar with aspirin, but analgesic, analgesic activity a little less than.
Recombined streptokinase is a kind of protein medicaments that adopts the recombinant DNA technology preparation; Its mechanism of action is to be combined into complex with plasminogen with 1: 1 mole ratio; Activate into fibrinolysin to plasminogen then; The hydrolysis of fibrinolysin catalysis thrombosis main matrix fibrin, thus effectively, thrombus specifically, reach the effect of treatment thrombotic disease.The present clinical dosage form of using is lyophilized injectable powder, is used for revascularizations such as acute myocardial infarction, DVT, does not still have the relevant report of its percutaneous dosing.
Hemorrhoid are one of the most common diseases that influence health of people and quality of life, also are one of recial diseases that sickness rate is the highest in the world wide, and the annual about amplitude with 16% of the sickness rate of China rises in recent years.At present, the hemorrhoid more than 90% adopt non-operative treatment to treat usually.The drug kinds that is used to treat hemorrhoid is more, and mostly chemosynthesis class medicine is peroral dosage form and is prone to cause the generation of general untoward reaction; Chinese medicine class suppository or ointment untoward reaction are light, mainly reach the effect of reducing swelling and alleviating pain through heat-clearing and toxic substances removing, hemostasia and promoting granulation, but because the course of treatment is long and drug withdrawal after be prone to repeatedly, and cause the patient must long-term prescription can produce effects; And suppository still has inconvenience such as the discomfort of use, administration time limitation, and Comparatively speaking, external preparation such as ointment or membrane more are prone to accepted by the patient.
Summary of the invention
The objective of the invention is to overcome defective of the prior art, a kind of new purposes and related application of sodium salicylate is provided.
The present invention at first discloses the purposes of sodium salicylate as penetrating agent in the external preparation, and said external preparation is for being the external preparation of the treatment hemorrhoid class disease of main pharmacodynamics composition with the recombined streptokinase.
Wherein, recombined streptokinase is by the colibacillus that efficiently expresses streptokinase genes, through fermentation, separation and highly purified after make purity＞95% (HPLC method, electrophoresis method).
Said hemorrhoid class disease be meant under the human body rectum end mucosa and under the anal canal skin venous plexus the formed soft vein of expansion and flexing group takes place; Comprising internal hemorrhoid, external hemorrhoid, mixed hemorrhoid, is the venous plexus generation varicose of anal orifice and rectal intestine bottom and anal mucosa and a kind of chronic disease of the one or more softish vein group that forms.
Further, the content of said sodium salicylate in the external preparation is 0.01-3%, preferred 0.1-2.5%.
The present invention also further discloses a kind of external preparation of treating hemorrhoid class disease, and its principal agent composition is that concentration is the recombined streptokinase of 80000IU-180000IU/g, preferred 100000IU-150000IU/g.Said external preparation also contain weight percent content be the sodium salicylate of 0.01-3% as penetrating agent, preferred 0.1-2.5%.
Said external preparation can be for percutaneous drug administration preparation or through tract mucosa delivery preparation, and further, said external preparation is ointment or suppository.
Since recombined streptokinase albumen exist molecular weight big, be prone to inactivation, be prone to degraded, be difficult for defective such as transdermal penetration; The preparation external preparation is difficult for reaching requirement at aspects such as stability, permeability, absorbances; After deliberation; The accessory formula of optimizing be with octadecanol, monoglyceride, vaseline, liquid Paraffin, glycerol, span, sodium salicylate and ethyl hydroxybenzoate jointly as adjuvant, wherein, sodium salicylate is as penetrating agent; The external preparation of this optimization of C is all doing well aspect stability, permeability, the absorbance, and adverse reaction rate such as local irritation, anaphylaxis is extremely low.
As one of preferred version; The external preparation of treatment hemorrhoid class disease of the present invention is the percutaneous dosing ointment; Its principal agent composition is that concentration is the recombined streptokinase of 100000IU-150000IU/g, comprises the adjuvant component (gross weight in ointment is a benchmark) of following weight percentage in the said ointment:
Octadecanol 5-20%
Monoglyceride 3-15%
Vaseline 2-20%
Liquid Paraffin 2-10%
Glycerol 5-10%
Span 0.5-2%
Ethyl hydroxybenzoate 0.05-0.5%
Sodium salicylate 0.1-2.5%.
The water for injection surplus
The method for preparing of ointment of the present invention is:
1) take by weighing sterilized octadecanol, monoglyceride, vaseline, liquid Paraffin, span, ethyl hydroxybenzoate by recipe quantity, heating makes complete fusion, stirs, and the decontamination that sieves is as decentralized photo I;
2) get a container in addition, take by weighing sterilized glycerol, sodium salicylate and water for injection mixing, the heating in water bath dissolving is sieved, as decentralized photo II.
3) then, temperature is controlled at 70-80 ℃, adopts the method for vacuum homogenizing, make 1), 2) particle diameter of biphase mixing and emulsifying and microgranule is controlled at 200nm-3 μ m;
4) recombined streptokinase is carried out protein protection after, handle through degerming;
5) with above-mentioned steps 3) emulsion that obtains continues to stir and when being cooled to 30-35 ℃, adds treated principal agent composition recombined streptokinase in the step 4), makes its mixing, continue to stir and naturally cool to room temperature promptly to get product.
The particle diameter of the ointment microgranule that above method for preparing obtains is superfine, is easy to transdermal, improves absorbance; And used the penetrating agent sodium salicylate that is more suitable for recombined streptokinase among the present invention, the concentration that makes principal agent arrive site of action improves greatly, and drug effect significantly strengthens.
As two of preferred version; The external preparation of treatment hemorrhoid class disease of the present invention is a suppository; Its principal agent composition is that concentration is the recombined streptokinase of 100000IU-150000IU/g, also comprises the adjuvant component (gross weight in suppository is a benchmark) of following weight percentage in the said suppository:
Hydrogenation cocos nucifera oil glycerol mixed ester 75-95%
Span 0.5-2.0%
Ethyl hydroxybenzoate 0.05-0.5%
Sodium salicylate 0.1-2.5%
The water for injection surplus
The method for preparing of suppository of the present invention is:
1) take by weighing sterilized hydrogenation cocos nucifera oil glycerol mixed ester, span, ethyl hydroxybenzoate by recipe quantity, heating makes complete fusion, stir, and the decontamination that sieves, subsequent use.
2) sodium salicylate is dissolved in water for injection, after the heating in water bath dissolving, this solution is added above-mentioned 1) in mixture in, stir.
3) recombined streptokinase is carried out protein protection after, handle through degerming;
4) with above-mentioned steps 2) mixture that obtains continues to stir and when being cooled to 30-35 ℃, adds treated principal agent composition recombined streptokinase in the step 3), stirs and makes its mixing, is filled into then in the suppository mould, and make it naturally cool to room temperature and promptly get product.
It is raw material that external preparation of the present invention adopts the recombined streptokinase of technique for gene engineering preparation, and warp adds suitable penetrating agent, processes to absorb the significant external preparation of good efficacy, and percutaneous or mucosa delivery are used for hemorrhoid class treatment of diseases.
Among the present invention, the recombined streptokinase ointment that the inventor uses the preparation of different penetrating agent has carried out the transdermal penetration test, and with do not add penetrating agent and carry out comparative study.The result shows, adopts the recombined streptokinase ointment of sodium salicylate as the penetrating agent preparation, and transdermal effect is best.
Ointment of the present invention is coated the hemorrhoid surface through the part, and through drug osmotic, the orientable blood stasis that acts on makes that thromboembolism, hematoma melt, pain relief, has short treating period, evident in efficacy, advantage that the untoward reaction rate is low.Owing to adopted the method for vacuum homogenizing; Make that the microgranule of this ointment is very tiny, and adopt protein protective agent to carry out pretreated recombined streptokinase, then more stable in preparation; Under the synergism of penetrating agent sodium salicylate; Transdermal barrier very easily, through site of action is brought into play good drug effect.
Suppository of the present invention through cavity/canal drug administration, under the body normal body temperature, can soften fusion rapidly, or be dissolved in juice, discharges medicine gradually and produces therapeutical effect, the treatment of the internal hemorrhoid of being more convenient for and mixed hemorrhoid.
The specific embodiment
Below enumerate specific embodiment with further elaboration the present invention, should be understood that instance is not to be used to limit protection scope of the present invention.
Embodiment 1 mice Transdermal absorption experimental study
Get the healthy male Kunming mouse, body weight 20-25g puts to death its disconnected neck; Cut off with the hair of shears, and use the scraper scraping, take off skin of abdomen abdominal part; Remove subcutaneous tissue and fat, inspection Corium Mus integrity (any breakage must not be arranged) is cleaned with normal saline; Be tiled on the aluminium foil, preserve subsequent use under-20 ℃ of conditions.
Adopt the two-chamber osmotic disperser, the isolated skin stratum corneum side upwards is fixed between two Room.Add an amount of protein stabilized buffer in the receiving chamber, carry out magnetic agitation with 300 rev/mins speed, a side connects the updip pipeline, can replenish reception liquid after making sampling.Add 1 * 10 in the diffuser casing
5IU recombined streptokinase and different penetrating agents (seeing table 1) are evenly coated skin surface.Whole device places 33 ℃ of waters bath with thermostatic control, and respectively at the 1st, 2,3,4,6,8h is from the receiving chamber 3ml that takes a sample, and additional equivalent is preheated to 33 ℃ buffer, and sample is carried out determining the protein quantity.The result shows that when adopting sodium salicylate as penetrating agent, recombined streptokinase transdermal penetration effect is best.
The percutaneous accumulation transit dose (mg/ml) of table 1 different formulations
The positive control drug effect research of embodiment 2 mice auricle swellings
Get 48 of regular grade Kunming mouses, 12 every group, male and female half and half; Be divided into three test group at random, be respectively recombined streptokinase and add three kinds of different penetrating agents and normal saline group (negative control), get xylene 0.05ml evenly be applied to mice left side ear before and after the two sides cause inflammation; 0.5h after, causing the mice of each test group and evenly to coat equivalent recombined streptokinase and three kinds of different penetrating agents on the scorching auricle respectively, penetrating agent concentration is with embodiment 1 (seeing table 2); Negative control group is coated normal saline, after 2 hours, the mice cervical vertebra is put to death from disconnected; Cut left and right sides ears along the auricle baseline, take off an auricle at same position respectively, on electronic balance, weigh with the 9mm card punch; Calculating two auricle weight differences is the swelling degree, inhibitory rate of intumesce=(the average swelling degree of the normal saline group-average swelling degree of administration the group)/average swelling degree of normal saline group * 100%
The result shows that recombined streptokinase adds that three test group of different penetrating agents all have the detumescence effect, and wherein, the improvement of the swelling degree of sodium salicylate group obviously is superior to other test group.
The detumescence effect of table 2 different formulations
| Prescription | Prescription A | Prescription B | Prescription C | Negative control group |
| Penetrating agent | Sodium salicylate | Azone | Menthol | / |
| Inhibitory rate of intumesce | 1.84±0.21 | 1.70±0.24 | 1.35±0.22 | 0 |
The preparation of embodiment 3 recombined streptokinase ointments
According to the form below formulation ointment
Preparation technology:
1) take by weighing sterilized octadecanol, monoglyceride, vaseline, liquid Paraffin, span, ethyl hydroxybenzoate by recipe quantity, heating makes complete fusion, stirs, and the decontamination that sieves is as decentralized photo I;
2) get a container in addition, take by weighing sterilized glycerol and sodium salicylate mixing, heating in water bath sieves, as decentralized photo II.
3) then, temperature is controlled at 70-80 ℃, adopts the method for vacuum homogenizing, make 1), 2) particle diameter of biphase mixing and emulsifying and microgranule is controlled at 200nm-3 μ m;
4) recombined streptokinase is carried out protein protection after, handle through degerming;
5) with the above-mentioned the 3rd) in emulsion continue to stir and when being cooled to 30-35 ℃, add the 4th) the treated principal agent composition of Xiang Zhongyi, make its mixing, continue to stir and naturally cool to room temperature promptly to get.
The pharmacodynamic study of pedal swelling model due to embodiment 4 rat carrageenans
Get 40 of rats, body weight 130-150g is divided into 5 groups at random, and 10 every group, male and female half and half give the four kinds of preparations (prescription A, B, C, D) 3 times among the embodiment 3, each 5 minutes at interval in the coating of right back sufficient sole of the foot portion respectively.After the last administration, measure each Mus foot sole of the foot thickness, then only, cause scorching back respectively at surveying sufficient sole of the foot thickness in 1,2,3,4 hour, swelling degree=(cause scorching metapedes sole of the foot thickness-cause scorching front foot sole of the foot thickness) in its right back sufficient plantar subcutaneous injection 1% carrageenin 0.1ml/.
The result shows, but four kinds of preparations all due to the on Carrageenan rat paw edema inhibitory action is arranged, but the swelling degree of prescription A group (sodium salicylate group) is improved and obviously is superior to other test group.
The drug effect of table 3 different formulations relatively
The preparation of embodiment 5 recombined streptokinase ointments
Adopt the method preparation ointment of embodiment 3 according to following table
The preparation of embodiment 6 recombined streptokinase suppositorys
According to following table prescription preparation suppository
The method for preparing of suppository of the present invention is:
1) take by weighing sterilized hydrogenation cocos nucifera oil glycerol mixed ester, span, ethyl hydroxybenzoate by recipe quantity, heating makes complete fusion, stir, and the decontamination that sieves, subsequent use.
2) sodium salicylate is dissolved in water for injection, after the heating in water bath dissolving, this solution is added above-mentioned 1) in mixture in, stir.
3) recombined streptokinase is carried out protein protection after, handle through degerming;
4) with above-mentioned steps 2) mixture that obtains continues to stir and when being cooled to 30-35 ℃, adds treated principal agent composition recombined streptokinase in the step 3), stirs and makes its mixing, is filled into then in the suppository mould, and make it naturally cool to room temperature and promptly get product.
The pharmacodynamic study of embodiment 7 rat Oleum Tiglii anus swelling models
Get 50 of rats, body weight 200-250g is divided into 5 groups at random, and 10 every group, male and female half and half are inserted the rat anus with the Oleum Tiglii mixed liquor, keep somewhere certain hour, observes in causing scorching back different time then, to confirm the most preferably parameters of living model.Insert different condition screenings such as anus indwelling time, age in rat week through mixed liquor consumption, cotton balls, confirm that most preferably condition is following: the proportioning of Oleum Tiglii mixed liquor is distilled water: pyridine: ether: 6% Oleum Tiglii=1: 4: 5: 10; Consumption is 0.16ml, soaks into 6 10 seconds of rat anal all ages of inserting behind the cotton balls with the ether light anaesthesia, and crissum swelling is obvious after 6 hours; Histological observation is visible, tissue edema, also significantly swelling around the serous coat under the mucosa; Normal mucosa wrinkle wall disappears; Mucomembranous epithelial cell is active to be reduced, vasodilation under the mucosa, and have leukocyte and fibrin to soak into.
After adopting above living model modeling, give four kinds of preparations among the embodiment 6 (prescription E, F, G, H) respectively, simultaneously with blank substrate as negative control.Before administration, after the administration, surveyed the diameter of whole anus surrounding tissue swelling in 1,2,4,6,8,10,12,24 hour, get the index of the average of its length two diameters, compare with blank substrate matched group as measured swelling degree.
The result shows that four kinds of preparations all can have significant inhibitory effect (P＜0.05) to rat crissum swelling due to the Oleum Tiglii, but the improvement of the swelling degree of prescription E group (sodium salicylate group) obviously is superior to other test group.
The preparation of embodiment 8 recombined streptokinase suppositorys
Adopt the method preparation suppository of embodiment 6 according to following table
Claims (10)
1. sodium salicylate is as the purposes of penetrating agent in the external preparation, and said external preparation is for being the external preparation of the treatment hemorrhoid class disease of main pharmacodynamics composition with the recombined streptokinase.
2. the purposes of sodium salicylate according to claim 1 is characterized in that said external preparation is a percutaneous drug administration preparation or through tract mucosa delivery preparation.
3. the purposes of sodium salicylate according to claim 1 is characterized in that said external preparation is ointment or suppository.
4. external preparation of treating hemorrhoid class disease, its principal agent composition is that concentration is the recombined streptokinase of 80000IU-180000IU/g, it is that the sodium salicylate of 0.01-3% is as penetrating agent that said external preparation also contains weight percent content.
5. external preparation as claimed in claim 4 is characterized in that, the preferred concentration of said recombined streptokinase is 100000IU-150000IU/g.
6. external preparation as claimed in claim 4 is characterized in that, the preferred weight percent content of said sodium salicylate is 0.1-2.5%.
7. external preparation as claimed in claim 4; It is characterized in that; Said external preparation is the percutaneous dosing ointment, and its principal agent composition is that concentration is the recombined streptokinase of 100000IU-150000IU/g, comprises the adjuvant component of following weight percentage in the said ointment:
Octadecanol 5-20%
Monoglyceride 3-15%
Vaseline 2-20%
Liquid Paraffin 2-10%
Glycerol 5-10%
Span 0.5-2%
Ethyl hydroxybenzoate 0.05-0.5%
Sodium salicylate 0.1-2.5%
The water for injection surplus.
8. like the said external preparation of claim 7, it is characterized in that said percutaneous dosing ointment adopts the method that comprises the following steps to make:
1) take by weighing sterilized octadecanol, monoglyceride, vaseline, liquid Paraffin, span, ethyl hydroxybenzoate by prescription, heating makes complete fusion, stirs, and the decontamination that sieves is as decentralized photo I;
2) get a container in addition, take by weighing sterilized glycerol, sodium salicylate and water for injection mixing, the heating in water bath dissolving is sieved, as decentralized photo II.
3) then, temperature is controlled at 70-80 ℃, adopts the method for vacuum homogenizing, make I, the particle diameter of the biphase mixing of II and emulsifying and microgranule is controlled at 200nm-3 μ m;
4) recombined streptokinase is carried out protein protection after, handle through degerming;
5) with above-mentioned steps 3) emulsion that obtains continues to stir and when being cooled to 30-35 ℃, adds treated principal agent composition recombined streptokinase in the step 4), makes its mixing, continue to stir also to naturally cool to room temperature and obtain product.
9. external preparation as claimed in claim 4 is characterized in that, said external preparation is a suppository, and its principal agent composition is that concentration is the recombined streptokinase of 100000IU-150000IU/g, also comprises the adjuvant component of following weight percentage in the said suppository:
Hydrogenation cocos nucifera oil glycerol mixed ester 75-95%
Span 0.5-2.0%
Ethyl hydroxybenzoate 0.05-0.5%
Sodium salicylate 0.1-2.5%
The water for injection surplus.
10. external preparation as claimed in claim 9 is characterized in that, said suppository adopts the method for preparing that comprises the following steps to make:
1) take by weighing sterilized hydrogenation cocos nucifera oil glycerol mixed ester, span, ethyl hydroxybenzoate by recipe quantity, heating makes complete fusion, stir, and the decontamination that sieves, subsequent use.
2) sodium salicylate is dissolved in water for injection, after the heating in water bath dissolving, this solution is added above-mentioned 1) in mixture in, stir.
3) recombined streptokinase is carried out protein protection after, handle through degerming;
4) with above-mentioned steps 2) mixture that obtains continues to stir and when being cooled to 30-35 ℃, adds treated principal agent composition recombined streptokinase in the step 3), stirs and makes its mixing, is filled into then in the suppository mould, and make it naturally cool to room temperature and obtain product.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010581178.1A CN102552916B (en) | 2010-12-09 | 2010-12-09 | New use of sodium salicylate |
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| CN201010581178.1A CN102552916B (en) | 2010-12-09 | 2010-12-09 | New use of sodium salicylate |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105963280A (en) * | 2016-06-30 | 2016-09-28 | 合肥华方医药科技有限公司 | Voglibose oral instant film and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1738602A (en) * | 2002-12-27 | 2006-02-22 | 遗传工程与生物技术中心 | Formulations for the rectal administration of thrombolytically-active agents |
-
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1738602A (en) * | 2002-12-27 | 2006-02-22 | 遗传工程与生物技术中心 | Formulations for the rectal administration of thrombolytically-active agents |
Non-Patent Citations (1)
| Title |
|---|
| 王洪钟等: "皮肤渗透促进剂－氮卓酮及其同系物合成的研究", 《日用化学工业》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105963280A (en) * | 2016-06-30 | 2016-09-28 | 合肥华方医药科技有限公司 | Voglibose oral instant film and preparation method thereof |
| CN105963280B (en) * | 2016-06-30 | 2018-11-06 | 合肥华方医药科技有限公司 | A kind of voglibose oral instant membrane and preparation method thereof |
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| CN102552916B (en) | 2014-04-23 |
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