CN105412226A - Application of salviae miltiorrhizae and flos carthami composition to enhancement of antithrombotic function of aspirin - Google Patents
Application of salviae miltiorrhizae and flos carthami composition to enhancement of antithrombotic function of aspirin Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
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Abstract
The invention discloses application of a salviae miltiorrhizae and flos carthami composition to enhancement of the antithrombotic function of aspirin. On the basis of the traditional Chinese medicine prescription compatibility theory and a large number of experiments and researches, the salviae miltiorrhizae and flos carthami composition is screened out and can remarkably inhibit the esterase activity of aspirin, the hydrolysis speed of aspirin is reduced, the acting time of aspirin is prolonged, aspirin resistance is inhibited, the antiplatelet function of aspirin is enhanced, the antithrombotic treatment effect can be enhanced by clinically using the salviae miltiorrhizae and flos carthami composition and aspirin, adverse effects are reduced, and application prospects are important.
Description
Technical field
The present invention relates to a kind of novelty teabag of Chinese medicine composition, be specifically related to Radix Salviae Miltiorrhizae Flos Carthami compositions and strengthening aspirin anti thrombotic action and suppressing aspirin esterase active and promote the application in aspirin antiplatelet effects.
Background technology
Aspirin is classical antipyretic-antalgic anti-inflammatory agent, and be one of most popular medicine in the world, the main uses of current aspirin is the medicine being used as prevention and cure of cardiovascular disease under low dose.
Aspirin is salicylic acid by gastrointestinal tract first pass effect and liver first-pass effect partial hydrolysis in absorption process, with prototype enter sanguimotor aspirin (50-70%) rapidly by the aspirin esterase hydrolyzed in liver and blood for salicylic acid.The hematoblastic COX-1 enzyme active center of aspirin energy acetylation, makes platelet permanent deactivation thus plays antiplatelet effects.Then antiplatelet effects is lost after aspirin hydrolyzes is salicylic acid.Therefore, aspirin esterase active determines the hydrolysis rate of aspirin, affects antiplatelet and the antithrombotic drug effect of aspirin.Aspirin resistance but fails to obtain patient's proposition of desirable platelet effects for those Aspirins.Aspirin resistance is defined as: some patients is taken in routine dose aspirin for treatment process in rule, does not reach the effect of the anticoagulant of expection, and the danger of recurring cardiovascular event clinically increases.Current existing large quantity research proves, the increase of aspirin esterase active is one of major reason causing aspirin resistance.
Therefore, necessary on the basis of prior art, research and develop curative effect reliable, can significantly reduce aspirin esterase active, antagonism aspirin resistance, strengthen aspirin antiplatelet effects, thus increase the medicine of aspirin anti thrombotic action.
Summary of the invention
Goal of the invention: technical problem to be solved by this invention overcomes the deficiencies in the prior art, by lot of experiments research screening, there is provided a kind of curative effect reliable, can significantly reduce aspirin esterase active, antagonism aspirin resistance, strengthen aspirin antiplatelet effects, thus reach the Chinese medicine composition strengthening aspirin anti thrombotic action.
Technical scheme: in order to realize above object, the technical scheme that the present invention takes is:
Radix Salviae Miltiorrhizae Flos Carthami compositions is suppressing the application in aspirin esterase active.
Preferably, above-described Radix Salviae Miltiorrhizae Flos Carthami compositions is suppressing the application in aspirin esterase active, wherein Radix Salviae Miltiorrhizae 3 parts of Flos Carthami 1 part.
Preferably, above-described Radix Salviae Miltiorrhizae Flos Carthami compositions is suppressing the application in aspirin esterase active, the oral formulations make the extract of Radix Salviae Miltiorrhizae 3 parts of Flos Carthami 1 part of compositions and pharmaceutically acceptable carrier or ejection preparation.
The invention provides Radix Salviae Miltiorrhizae Flos Carthami compositions and promote the application in aspirin antiplatelet in gathering.
Preferably, above-described Radix Salviae Miltiorrhizae Flos Carthami compositions is promoting the application in aspirin antiplatelet aggregation, and compositions is made up of Radix Salviae Miltiorrhizae 3 parts of Flos Carthami 1 part.
Preferably, above-described Radix Salviae Miltiorrhizae Flos Carthami compositions is promoting the application in aspirin antiplatelet aggregation, the oral formulations make the extract of Radix Salviae Miltiorrhizae 3 parts of Flos Carthami 1 part of compositions and pharmaceutically acceptable carrier or ejection preparation.
The present invention also provides the application of Radix Salviae Miltiorrhizae Flos Carthami compositions in control aspirin resistance in addition.
Preferably, the application of above-described Radix Salviae Miltiorrhizae Flos Carthami compositions in control aspirin resistance, the compositions of Radix Salviae Miltiorrhizae 3 parts of Flos Carthami 1 part composition.
Preferably, the application of above-described Radix Salviae Miltiorrhizae Flos Carthami compositions in control aspirin resistance, the oral formulations that the extract of Radix Salviae Miltiorrhizae 3 parts of Flos Carthami 1 part of compositions and pharmaceutically acceptable carrier are made or ejection preparation.
During as compositions provided by the invention made Radix Salviae Miltiorrhizae Flos Carthami composite injection, get Radix Salviae Miltiorrhizae 3 parts and 1 part, Flos Carthami, decoct with water twice, each 60min, filter, filtrate merges the clear paste of simmer down to relative density 1.20-1.30 (65 DEG C), add ethanol to alcohol content 75-80%, cold preservation, get supernatant, reclaim ethanol and the clear paste of simmer down to relative density 1.20-1.30, add ethanol to alcohol content 80-85%, cold preservation, get supernatant, add the active carbon being about inventory 1%, stir 30min, leave standstill, filter, filtrate recycling ethanol is extremely without alcohol taste, add water to amount of preparation, stir evenly, heated and boiled 40-50min, cold preservation, filter, filtrate is concentrated into 1/3 of amount of preparation, cold preservation, filter, filtrate by NaOH solution adjust ph to 6.5-7.5, heated and boiled 40-50min, add the active carbon being about amount of liquid medicine 0.5%, stir evenly, fluid temperature is down to 50-60 DEG C, leave standstill, filter, filtrate is after ultrafiltration, add the active carbon being about amount of liquid medicine 0.5%, boil, filter, filtrate injects water to 1000mL, adjust ph is to 6.5-7.5, filter, embedding, sterilizing.
Beneficial effect: Radix Salviae Miltiorrhizae Flos Carthami compositions provided by the invention can significantly suppress aspirin esterase active, the aspirin hydrolyzes that slows down speed, extend aspirin action time, antagonism aspirin resistance, strengthen aspirin antiplatelet effects, antithrombotic curative effect can be strengthened with aspirin combination medication clinically, reduce untoward reaction, there is important application prospect.
Accompanying drawing explanation
The Radix Salviae Miltiorrhizae Flos Carthami compositions of Fig. 1 different ratio and dosage form affects block diagram to plasma substance P level.
Fig. 2 is that in body, blood plasma aspirin esterase active measures block diagram.
Fig. 3 is that external blood plasma aspirin esterase active measures block diagram.
Fig. 4 is blood plasma TXB
2level determination block diagram.
Detailed description of the invention
Below in conjunction with specific embodiment, illustrate the present invention further, these embodiments should be understood only be not used in for illustration of the present invention and limit the scope of the invention, after having read the present invention, the amendment of those skilled in the art to the various equivalent form of value of the present invention has all fallen within the application's claims limited range.
The Radix Salviae Miltiorrhizae Flos Carthami compositions of embodiment 1 different ratio and dosage form is on the impact of low-dosage aspirin antiplatelet effects
1. experimental technique
1.1 experiment material
Radix Salviae Miltiorrhizae Flos Carthami composite injection: Radix Salviae Miltiorrhizae Flos Carthami (C1,1 part, the Radix Salviae Miltiorrhizae 3 parts-Flos Carthami of getting Different Weight ratio, C2,1 part, Radix Salviae Miltiorrhizae 1 part-Flos Carthami, C3, 3 parts, Radix Salviae Miltiorrhizae 1 part-Flos Carthami), decoct with water twice, each 60min, filter, filtrate merges the clear paste of simmer down to relative density 1.20-1.30 (65 DEG C), add ethanol to alcohol content 75-80%, cold preservation, get supernatant, reclaim ethanol and the clear paste of simmer down to relative density 1.20-1.30, add ethanol to alcohol content 80-85%, cold preservation, get supernatant, add the active carbon being about inventory 1%, stir 30min, leave standstill, filter, filtrate recycling ethanol is extremely without alcohol taste, add water to amount of preparation, stir evenly, heated and boiled 40-50min, cold preservation, filter, filtrate is concentrated into 1/3 of amount of preparation, cold preservation, filter, filtrate by NaOH solution adjust ph to 6.5-7.5, heated and boiled 40-50min, add the active carbon being about amount of liquid medicine 0.5%, stir evenly, fluid temperature is down to 50-60 DEG C, leave standstill, filter, filtrate is after ultrafiltration, add the active carbon being about amount of liquid medicine 0.%, boil, filter, filtrate injects water to 1000ml, adjust ph is to 6.5-7.5, filter, embedding, sterilizing.
Radix Salviae Miltiorrhizae Flos Carthami composition grain: get Radix Salviae Miltiorrhizae 3 parts, 1 part, Flos Carthami, decoct with water twice, each 60min, filter, filtrate merges the clear paste of simmer down to relative density 1.20-1.30 (65 DEG C), add ethanol to alcohol content 75-80%, cold preservation, get supernatant, reclaim ethanol and the clear paste of simmer down to relative density 1.20-1.30, add the mixture (sucrose: dextrin=3:1) of suitable amount of sucrose powder and dextrin and the ethanol of appropriate 70%, mix becomes soft material, extrudes sieve (12-14 order) and makes granule, 60 DEG C of dryings, granulate.
1.2 experimental program
48 rats are divided into 6 groups (A, B, C, D, E, F) at random, often organize 8.According to rat body weight every day at set time administration (9:00am-12:00am), successive administration 14 days.Before first time administration, fasting 12 hours, freely drinks water.A group (CTL) rat rule every day feedwater feeding; B group (ASA) rat gavage every day aspirin solution; Gavage aspirin solution after C group (ASA-C1) tail vein injection every day Radix Salviae Miltiorrhizae Flos Carthami composite injection C1; Gavage aspirin solution after D group (ASA-C2) tail vein injection every day Radix Salviae Miltiorrhizae Flos Carthami composite injection C2; Gavage aspirin solution after E group (ASA-C3) tail vein injection every day Radix Salviae Miltiorrhizae Flos Carthami composite injection C3; Gavage aspirin solution after F group (ASA-K) gavage every day Radix Salviae Miltiorrhizae Flos Carthami composition grain.The dosage of aspirin and Radix Salviae Miltiorrhizae-Flos Carthami compositions every day is respectively 10.41mg/kg and 4.16ml/kg.Wherein, the crude drug dosage of Radix Salviae Miltiorrhizae Flos Carthami composite injection and granule every day is suitable.All rat eye sockets were got blood 0.5mL in 15th day, be placed in the PE pipe (blood is 9 to 1 with the volume ratio of anticoagulant) containing 3.8% liquor sodii citratis, the centrifugal 10min of 13000 × g gets supernatant and obtains plasma sample.Thromboxane element B2 (TXB2) the kit measurement blood plasma TXB of Bioengineering Research Institute is built up according to Nanjing
2level.
1.31.5 statistical procedures
Experimental data represents with meansigma methods ± S.E.M.Group difference adopts nonparametric Mann-Whitney inspection.Significant difference is set as P<0.05.
2. experimental result
(* represents with CTL group than there being significant difference (P<0.05) as shown in Figure 1; # represents there is significant difference (P<0.05) compared with ASA group).Low-dosage aspirin has significant antiplatelet effects, and continuous use can cause plasma substance P level significantly to decline (P<0.05) for 14 days.When low-dosage aspirin and Radix Salviae Miltiorrhizae Flos Carthami compositions drug combination, plasma substance P level declines (P<0.05) further.When wherein Radix Salviae Miltiorrhizae Flos Carthami compositions proportioning is 3:1, other two kinds of proportionings are obviously better than on the impact of plasma substance P level; In addition, the decline degree of Radix Salviae Miltiorrhizae Flos Carthami composite injection to plasma substance P level is also greater than Radix Salviae Miltiorrhizae Flos Carthami composition grain.In sum, the most remarkable to the inhibitory action of plasma substance P level when Radix Salviae Miltiorrhizae Flos Carthami compositions makes injection according to 3:1 proportioning, its degree strengthening low-dosage aspirin antiplatelet effects is also more remarkable.
Embodiment 2 Radix Salviae Miltiorrhizae Flos Carthami composite injection is on the impact of aspirin esterase active
1. experimental technique
1.1 blood plasma aspirin esterase actives measure
In 890 μ LTris buffer, add 100 μ L blank plasmas and 10 μ L aspirin hydrochloric acid solutions, after vortex 30s, 20min is hatched in 37 DEG C of water-baths.Get 100 μ L reactant liquors add 100 μ L inner mark solution stopped reactions and precipitate a small amount of albumen, the centrifugal 10min of 13000 × g, draw 150 μ L supernatant sample introductions.Determination of Salicylic Acid application UPLC-TQ-MS measures.The compound method of aspirin hydrochloric acid solution is: be dissolved in by 1.08mg aspirin (Aspirin concentrations is 1mM) in 6mL0.1M hydrochloric acid.The compound method of Tris buffer is: by 0.2423g Tris (Tris) and 2.22g calcium chloride (CaCl
2) be dissolved in 100mL ultra-pure water, adjust pH to be 7.4 with 1M hydrochloric acid.The reaction system (namely 990 μ LTris buffer add 10 μ L aspirin hydrochloric acid solutions) not adding blank plasma is blank.By pH7.4, temperature 37 DEG C, concentration of substrate is in the reaction system of 1mM, and every milliliter of blood plasma generation per minute 1 μm of ol salicylic acid is defined as 1 aspirin esterase activity unit (U).
In 1.2 bodies, blood plasma aspirin esterase active measures
20 male SD rats (body weight 250-300g) are divided at random blank group and administration group, often organize 10.Blank group rule every day feedwater feeding, injection (the Radix Salviae Miltiorrhizae Flos Carthami composite injection C1 of Radix Salviae Miltiorrhizae 3 parts of Flos Carthami 1 part preparation that administration group every day provides according to the rat body weight tail vein embodiment of the present invention 1, hereinafter referred to as injection C1) 4.16mL/kg, successive administration 14 days.15th day respectively before administration, 1min after administration, 15min and 60min eye socket gets blood 0.3mL, is placed in the PE pipe (blood is 9 to 1 with the volume ratio of anticoagulant) containing 3.8% liquor sodii citratis, and the centrifugal 10min of 13000 × g gets supernatant and obtains plasma sample.Under 1.1, measure blood plasma aspirin esterase active, result as shown in Figure 2.
1.3 external blood plasma aspirin esterase actives measure
Get fresh blank rat plasma, be divided into 30 parts at random, every part of 100 μ L.S group (1-10 part) adds in 890 μ LTris buffer and 10 μ L aspirin hydrochloric acid solutions; C1 group (11-20 part) adds in 880 μ LTris buffer, 10 μ L aspirin hydrochloric acid solutions and 10 μ L injection C1 (in this system, injection C1 dilutes 100 times); C2 group (21-30 part) adds in 790 μ LTris buffer, 10 μ L aspirin hydrochloric acid solutions and 100 μ L Radix Salviae Miltiorrhizae Flos Carthamis composite injection C1 (in this system, injection C1 dilutes 10 times).Under 1.1, measure blood plasma aspirin esterase active, result as shown in Figure 3.
1.4 statistical procedures
Experimental data represents with meansigma methods ± S.E.M.Group difference adopts nonparametric Mann-Whitney inspection.Significant difference is set as P<0.05.
2. experimental result
In 2.1 bodies, blood plasma aspirin esterase active measures
Blood plasma aspirin esterase active measurement result display before administration in 15th day, injection C1 successive administration causes blood plasma aspirin esterase active significantly to decline (P<0.05) for 14 days, shows that the overall activity of Radix Salviae Miltiorrhizae Flos Carthami composite injection C1 long term administration provided by the invention to blood plasma aspirin esterase exists obvious inhibitory action.
After Radix Salviae Miltiorrhizae Flos Carthami composite injection C1 tail vein injection provided by the invention enters blood circulation, each component blood concentration reaches peak value immediately, and each component blood concentration declines (blood drug level: 1min>5min>60min after administration) all gradually subsequently.Blood plasma aspirin esterase active measurement result shows, Radix Salviae Miltiorrhizae Flos Carthami composite injection C1 blood drug level is higher, larger to the suppression degree of aspirin esterase active, show that Radix Salviae Miltiorrhizae Flos Carthami composite injection C1 is relevant to concentration to the effect of blood plasma aspirin esterase inhibition, this effect is that Radix Salviae Miltiorrhizae Flos Carthami composite injection C1 direct interference blood plasma aspirin esterase is to the result of aspirin hydrolyzes effect.
2.2 external blood plasma aspirin esterase actives measure
As shown in Figure 4, external blood plasma aspirin esterase active measurement result, shows that Radix Salviae Miltiorrhizae Flos Carthami composite injection C1 exists direct repression (P<0.05) to blood plasma aspirin esterase further.This inhibitory action is concentration dependent, does not make significant difference when showing as Radix Salviae Miltiorrhizae Flos Carthami composite injection C1 low concentration to blood plasma aspirin esterase active, then significantly suppresses blood plasma aspirin esterase active during high concentration.
Above experimental result shows, Radix Salviae Miltiorrhizae Flos Carthami compositions provided by the invention significantly suppresses aspirin esterase active, the aspirin hydrolyzes that slows down speed, extend aspirin action time, collaborative low-dosage aspirin reduces plasma substance P level further, antagonism aspirin resistance, strengthen aspirin antiplatelet effects, antithrombotic curative effect can be strengthened with aspirin combination medication clinically, reduce untoward reaction, there is important application prospect.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the prerequisite not departing from the principle of the invention and design; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (8)
1. Radix Salviae Miltiorrhizae Flos Carthami compositions is strengthening the application in aspirin anti thrombotic action.
2. Radix Salviae Miltiorrhizae Flos Carthami compositions is strengthening the application in aspirin antiplatelet aggregation.
3. Radix Salviae Miltiorrhizae Flos Carthami compositions is suppressing the application in aspirin esterase active.
4. the application of Radix Salviae Miltiorrhizae Flos Carthami compositions in control aspirin resistance.
5. Radix Salviae Miltiorrhizae Flos Carthami compositions according to claims 1 to 4, is characterized in that, it is by Radix Salviae Miltiorrhizae 1 ~ 5 part, Flos Carthami 1 ~ 3 part of compositions formed.
6. Radix Salviae Miltiorrhizae Flos Carthami compositions according to claims 1 to 4, is characterized in that, it is by Radix Salviae Miltiorrhizae 2 ~ 4 parts, Flos Carthami 1 part of compositions formed.
7. Radix Salviae Miltiorrhizae Flos Carthami compositions according to claims 1 to 4, is characterized in that, it is by Radix Salviae Miltiorrhizae 3 parts, Flos Carthami 1 part of compositions formed.
8. Radix Salviae Miltiorrhizae Flos Carthami compositions according to claims 1 to 4, is characterized in that, the extract of Radix Salviae Miltiorrhizae, Flos Carthami compositions and pharmaceutically acceptable carrier are made oral formulations or ejection preparation.
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Cited By (1)
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| CN105920096A (en) * | 2016-06-12 | 2016-09-07 | 南京中医药大学 | Composition with salviae miltiorrhiza and safflower as well as preparation method and application thereof |
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Application publication date: 20160323 |