CN109589331B - External medicine for inhibiting postoperative venous thrombosis and application thereof - Google Patents
External medicine for inhibiting postoperative venous thrombosis and application thereof Download PDFInfo
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Abstract
The invention belongs to the field of medicines, and particularly relates to an external medicine for inhibiting postoperative venous thrombosis and application thereof. The external medicine for inhibiting postoperative venous thrombosis is xanthohumol or a composition of xanthohumol and harpagoside. The external medicine for inhibiting postoperative venous thrombosis is preferably an external gel. Wherein the external medicament of the composition of the xanthohumol and the harpagoside comprises the following components in parts by weight: 3 parts of xanthohumol and 5-7 parts of harpagoside. The external medicinal auxiliary materials used as the external gel comprise: carbomer 940, 95% ethanol, glycerol, triethanolamine and distilled water. The external medicine for inhibiting postoperative venous thrombosis has obvious inhibition effect on thrombosis after preoperative or postoperative administration, and does not increase bleeding risk.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to an external medicine for inhibiting postoperative venous thrombosis and application thereof.
Background
Characteristic procoagulant and anticoagulant substances are present in the blood system. For most people, under normal conditions, the procoagulant and anticoagulant systems are in a state of dynamic equilibrium in vivo. In the process of operation or trauma and the like, when bleeding occurs, the body can promote the blood coagulation of the wound through the blood coagulation system, so as to avoid excessive blood loss. This homeostatic mechanism is one of the ways in which the body achieves self-protection.
The surgical procedure damages the blood vessels, disrupts the balance between the coagulation and fibrinolytic systems, thereby inducing a hypercoagulable state, easily leading to thrombosis. Postoperative venous thrombosis occurs primarily in veins that flow slowly. Such as cesarean section, knee or hip replacement, percutaneous coronary stenting, etc., all have the potential to induce post-operative venous thrombosis. Because the thrombolysis capability of the existing thrombolysis medicines is relatively limited, the formed thrombus cannot be completely dissolved, especially, the time window of thrombolysis is extremely limited, and the hemorrhagic risk is easily caused. Prophylactic administration is therefore the main treatment to avoid postoperative venous thrombosis.
Anti-platelet aggregation drugs are currently the main drugs for preventing postoperative venous thrombosis. Commonly used drugs such as aspirin, clopidogrel, rivaroxaban, warfarin, ticagrelor, cilostazol, tirofiban and the like. These drugs are usually administered before or after surgery, especially during the risk period of venous thrombosis after surgery, in order to prevent thrombosis. Wherein, aspirin mainly plays a role in resisting thrombus by inhibiting cyclooxygenase and inhibiting thromboxane. Not all cyclooxygenase inhibitors have an antithrombotic effect. Such as celecoxib, ibuprofen, and the like. Clopidogrel exerts antithrombotic effect by inhibiting platelet membrane adenosine diphosphate receptor. These drugs are also commonly used in combination clinically. However, some patients are resistant to the above drugs and require replacement.
Traditional Chinese medicines have been clinically used for preventing postoperative venous thrombosis, and the effectiveness of combined use with anti-platelet aggregation medicines has also been verified by clinical results. Most of the commonly used traditional Chinese medicines are traditional Chinese medicines or traditional Chinese medicine compound medicines with the functions of promoting blood circulation to remove blood stasis or tonifying qi and promoting blood circulation. Of the compound Chinese medicines, the application frequency of angelica, red peony root, salvia miltiorrhiza, suberect spatholobus stem, astragalus, ginseng, codonopsis pilosula, safflower, largehead atractylodes rhizome, coix seed and the like is the highest. Radix astragali, radix Notoginseng, and Hirudo are also widely used. The typical traditional Chinese medicine compound for treating postoperative venous thrombosis is Xueshuantong. The prescription comprises astragalus root, red sage root, scrophularia root, notoginseng, etc. Wherein the Notoginseng radix total saponin in Notoginseng radix has effect of preventing thrombosis, and the radix astragali total saponin in radix astragali also has effect of preventing thrombosis. Salvianolic acid B and tanshinone IIA in Saviae Miltiorrhizae radix also have antithrombotic effect.
Radix scrophulariae is applied to various antithrombotic traditional Chinese medicines, but specific components of radix scrophulariae for resisting thrombus are not clearly researched. Harpagoside is a chemical substance existing in radix scrophulariae, and researches show that harpagoside can resist damage caused by hydrogen peroxide, but has no research and report on whether the harpagoside has an antithrombotic effect.
Xanthohumol is an active substance present in hops and has been widely studied. Known activities include neuroprotection, anti-oxidation, anti-tumor, etc., and have inhibitory effects on cyclooxygenase-1 and 2.
Disclosure of Invention
In view of the above problems, it is an object of the present invention to provide an external use medicine for inhibiting postoperative venous thrombosis, so as to prevent postoperative venous thrombosis and reduce postoperative complications.
In order to achieve the purpose, the invention adopts the technical scheme that:
a topical medicine for inhibiting postoperative venous thrombosis comprises topical medicinal adjuvants and xanthohumol.
Preferably, the external medicine for inhibiting postoperative venous thrombosis is prepared from external medicine auxiliary materials, xanthohumol and harpagoside.
Further preferably, the external medicament for inhibiting postoperative venous thrombosis comprises the following components in parts by weight: 3 parts of xanthohumol and 5-7 parts of harpagoside.
Preferably, the external medicament for inhibiting postoperative venous thrombosis comprises the following components in parts by weight: 3 parts of xanthohumol and 5 parts of harpagoside.
Preferably, the external medicament for inhibiting postoperative venous thrombosis comprises the following components in parts by weight: 3 parts of xanthohumol and 6 parts of harpagoside.
Preferably, the external medicament for inhibiting postoperative venous thrombosis comprises the following components in parts by weight: 3 parts of xanthohumol and 7 parts of harpagoside.
Preferably, the external medicine for inhibiting postoperative venous thrombosis is external gel.
Preferably, the external medicinal auxiliary materials of the external gel comprise: carbomer 940, 95% ethanol, glycerol, triethanolamine and distilled water.
As a preferable scheme, the formula and the preparation method of the external gel are as follows:
xanthohumol 1g
Carbomer 9401 g
95% ethanol 20g
Glycerol 10g
Triethanolamine 1.5g
Distilled water to 100g
Preparation:
adding distilled water into the carbomer 940 with the formula amount to prepare a solution with the mass concentration of 4%, standing overnight and fully swelling;
uniformly mixing 95% ethanol, xanthohumol and glycerol according to the prescription amount, adding the mixture into the carbomer 940 solution, uniformly mixing, dripping triethanolamine according to the prescription amount while stirring to form gel, adding distilled water to 100g, and uniformly stirring to obtain the gel.
As another preferred scheme, the formula and preparation method of the external gel are as follows:
xanthohumol 0.3g
Harpagophytum procumbens 0.7 g
Carbomer 9401 g
95% ethanol 20g
20g of glycerol
Triethanolamine 1.5g
Distilled water to 100g
Preparation:
adding distilled water into the carbomer 940 with the formula amount to prepare a solution with the mass concentration of 4%, standing overnight and fully swelling;
uniformly mixing 95% ethanol, harpagoside, xanthohumol and glycerol according to the prescription amount, adding the mixture into the carbomer 940 solution, uniformly mixing, dripping triethanolamine according to the prescription amount while stirring to form gel, adding distilled water to 100g, and uniformly stirring to obtain the product.
As another preferable scheme, the formulation and preparation method of the external gel are as follows:
xanthohumol 0.3g
Harpagophytum procumbens 0.5 g
Carbomer 9401 g
95% ethanol 20g
15g of glycerol
Triethanolamine 1.5g
Distilled water to 100g
Preparation:
adding distilled water into the carbomer 940 with the formula amount to prepare a solution with the mass concentration of 4%, standing overnight and fully swelling;
uniformly mixing 95% ethanol, harpagoside, xanthohumol and glycerol according to the prescription amount, adding the mixture into the carbomer 940 solution, uniformly mixing, dripping triethanolamine according to the prescription amount while stirring to form gel, adding distilled water to 100g, and uniformly stirring to obtain the product.
As another preferable scheme, the formula and preparation method of the external gel are as follows:
xanthohumol 0.3g
Harpagophytum procumbens 0.6 g
Carbomer 9401 g
95% ethanol 20g
15g of glycerol
Triethanolamine 1.5g
Distilled water to 100g
Preparation:
adding distilled water into the carbomer 940 with the formula amount to prepare a solution with the mass concentration of 4%, standing overnight and fully swelling;
uniformly mixing 95% ethanol, harpagoside, xanthohumol and glycerol according to the prescription amount, adding the mixture into the carbomer 940 solution, uniformly mixing, dripping triethanolamine according to the prescription amount while stirring to form gel, adding distilled water to 100g, and uniformly stirring to obtain the product.
In another aspect of the invention, the application of the external medicament for inhibiting postoperative venous thrombosis in preparing a medicament for inhibiting postoperative venous thrombosis is also provided.
The Xanthohumol is named as Xanthohumol in English and has CAS number of 6754-58-1.
The Harpagoside is Harpagoside in English name and CAS number 19210-12-9.
The external medicine for inhibiting postoperative venous thrombosis can be used for short-term prevention before or after operation. The topical application can be applied to the affected part where postoperative thrombosis is likely to occur, such as the lower limb. The external medicine for inhibiting postoperative venous thrombosis has an obvious antithrombotic effect on an animal model, particularly has a more obvious effect of the external combination of xanthohumol and harpagoside, and has no bleeding risk.
Detailed Description
The practice of the invention is explained and illustrated below with reference to specific examples.
Example 1 external gel for inhibiting postoperative venous thrombosis
Xanthohumol 1g
Carbomer 9401 g
95% ethanol 20g
Glycerol 10g
Triethanolamine 1.5g
Distilled water to 100g
Preparation:
adding distilled water into the carbomer 940 with the formula amount to prepare a solution with the mass concentration of 4%, standing overnight and fully swelling;
uniformly mixing 95% ethanol, xanthohumol and glycerol according to the prescription amount, adding the mixture into the carbomer 940 solution, uniformly mixing, dripping triethanolamine according to the prescription amount while stirring to form gel, adding distilled water to 100g, and uniformly stirring to obtain the gel.
Example 2 external gel for inhibiting postoperative venous thrombosis
Xanthohumol 0.3g
Harpagophytum procumbens 0.7 g
Carbomer 9401 g
95% ethanol 20g
20g of glycerol
Triethanolamine 1.5g
Distilled water to 100g
Preparation:
adding distilled water into the carbomer 940 with the formula amount to prepare a solution with the mass concentration of 4%, standing overnight and fully swelling;
uniformly mixing 95% ethanol, harpagoside, xanthohumol and glycerol according to the prescription amount, adding the mixture into the carbomer 940 solution, uniformly mixing, dripping triethanolamine according to the prescription amount while stirring to form gel, adding distilled water to 100g, and uniformly stirring to obtain the product.
Example 3 external gel for inhibiting postoperative venous thrombosis
As another preferable scheme, the formulation and preparation method of the external gel are as follows:
xanthohumol 0.3g
Harpagophytum procumbens 0.5 g
Carbomer 9401 g
95% ethanol 20g
15g of glycerol
Triethanolamine 1.5g
Distilled water to 100g
Preparation:
adding distilled water into the carbomer 940 with the formula amount to prepare a solution with the mass concentration of 4%, standing overnight and fully swelling;
uniformly mixing 95% ethanol, harpagoside, xanthohumol and glycerol according to the prescription amount, adding the mixture into the carbomer 940 solution, uniformly mixing, dripping triethanolamine according to the prescription amount while stirring to form gel, adding distilled water to 100g, and uniformly stirring to obtain the product.
Example 4 external gel for inhibiting postoperative venous thrombosis
Xanthohumol 0.3g
Harpagophytum procumbens 0.6 g
Carbomer 9401 g
95% ethanol 20g
15g of glycerol
Triethanolamine 1.5g
Distilled water to 100g
Preparation:
adding distilled water into the carbomer 940 with the formula amount to prepare a solution with the mass concentration of 4%, standing overnight and fully swelling;
uniformly mixing 95% ethanol, harpagoside, xanthohumol and glycerol according to the prescription amount, adding the mixture into the carbomer 940 solution, uniformly mixing, dripping triethanolamine according to the prescription amount while stirring to form gel, adding distilled water to 100g, and uniformly stirring to obtain the product.
Example 5 study of inhibitory Effect of xanthohumol and Harpagophytum procumbens on thrombosis in rats
1. Experimental animals and breeding
40 ordinary Wistar rats with male body weight of 200-220 g. Feeding animals in a common room, wherein the temperature is 20-26 ℃, the humidity is 40-70%, and the ventilation frequency is as follows: 10-15 times per hour, and 12 hours of illumination every day.
2. Grouping and administration of drugs
Rats were randomly divided into 5 groups of 8 rats each, shaved by electric push on the back, dosed and molded.
The first group was solvent group, which was coated with dimethyl sulfoxide on the back 1 time a day for 30 consecutive days.
The second group is a xanthohumol group, and the back is applied with xanthohumol dimethyl sulfoxide solution 1 time per day for 30 consecutive days, and each animal is applied with xanthohumol 9mg each time.
The third group is harpagoside group, and harpagoside dimethyl sulfoxide solution is applied to the back for 30 consecutive days 1 time per day, and 21mg of harpagoside is applied to each animal.
And the fourth group is a low-dosage composition group, wherein the back of the fourth group is coated with xanthohumol and harpagoside dimethyl sulfoxide solution 1 time a day for 30 consecutive days, and each animal is coated with xanthohumol 9mg and harpagoside 15mg each time.
The fifth group is a high-dosage composition group, and the back of the fifth group is coated with xanthohumol and harpagoside dimethyl sulfoxide solution 1 time a day for 30 consecutive days, and each animal is coated with xanthohumol 9mg and harpagoside 21mg each time.
3. Modeling and inspection index
Performing postoperative thrombosis on day 28, and puncturing the middle part of each rat tail vein by a syringe needle for 0.2cm to simulate operative vascular injury; then, a 4% carrageenan solution, 0.2ml each, was injected subcutaneously into the hind toe foot of each rat. And 4 hours after the administration on the 30 th day, observing the color change of the skin at the tail tip part, and judging the thrombosis condition. Rats were anesthetized and the tail vein thrombus length was measured for each rat. The rats in each group were then sacrificed and the heart, liver, spleen, lung, stomach, and digestive tract were observed for bleeding.
4. Results of the experiment
The rats in each group showed tail vein thrombosis in different degrees, and the appearance of the tail part was dark red, while the serious rats were purplish black. Indicating that the model is successfully established.
The rats in each group were sacrificed and no bleeding in the heart, liver, spleen, lung, stomach, and digestive tract was observed in general, indicating that the treatment was performed without the risk of bleeding induction by transdermal administration of the drug for 30 days.
Statistics and comparison between groups were performed on the tail vein thrombus length of each group of rats, and the results are shown in the following table:
note that in the Table, # indicates that p <0.05 compared to the first group, the solvent group; # indicates p <0.01 compared to the first group, solvent group; denotes a xanthohumol group p <0.05 from the second, xanthohumol group; denotes the xanthohumol group p <0.01 from the second group, xanthohumol group.
5. Conclusion of the experiment
The xanthohumol is independently externally applied and the xanthohumol and harpagoside are jointly externally applied, and when the xanthohumol and the harpagoside are both applied before and after the model is built, the administration is carried out for 30 days continuously, so that the anti-thrombotic effect on rats with postoperative thrombosis is remarkable, and the bleeding risk is not increased.
Claims (5)
1. An external medicine for inhibiting postoperative venous thrombosis is characterized in that the external medicine for inhibiting postoperative venous thrombosis is prepared from external medicine auxiliary materials, xanthohumol and harpagoside; the external medicine for inhibiting postoperative venous thrombosis comprises the following components in parts by weight: 3 parts of xanthohumol and 5-7 parts of harpagoside; the external medicine for inhibiting postoperative venous thrombosis is external gel; the external medicinal auxiliary materials of the external gel comprise: carbomer 940, 95% ethanol, glycerol, triethanolamine and distilled water.
2. The external medicine for inhibiting postoperative venous thrombosis according to claim 1, wherein the external medicine for inhibiting postoperative venous thrombosis comprises the following components in parts by weight: 3 parts of xanthohumol and 5 parts of harpagoside.
3. The external medicine for inhibiting postoperative venous thrombosis according to claim 1, wherein the external medicine for inhibiting postoperative venous thrombosis comprises the following components in parts by weight: 3 parts of xanthohumol and 6 parts of harpagoside.
4. The external medicine for inhibiting postoperative venous thrombosis according to claim 1, wherein the external medicine for inhibiting postoperative venous thrombosis comprises the following components in parts by weight: 3 parts of xanthohumol and 7 parts of harpagoside.
5. Use of the external drug for inhibiting postoperative venous thrombosis according to claim 1 or 2 in the preparation of a drug for inhibiting postoperative venous thrombosis.
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| AU2002350272B1 (en) * | 2001-12-13 | 2003-06-23 | Vital Health Sciences Pty Ltd | Transdermal transport of compounds |
| US20060253100A1 (en) * | 2004-10-22 | 2006-11-09 | Medtronic, Inc. | Systems and Methods to Treat Pain Locally |
| WO2007016578A2 (en) * | 2005-07-29 | 2007-02-08 | Bioactives, Inc. | Prenylflavonoid formulations |
| CN103257188B (en) * | 2013-01-05 | 2014-04-02 | 中山大学 | Construction method for compound thrombus clearing preparation bioactivity chromatography finger print |
| CN104147032B (en) * | 2014-07-29 | 2016-07-27 | 广东众生药业股份有限公司 | A kind of pharmaceutical composition for preventing and treating cerebral infarction relevant disease and its production and use |
| CN104825359A (en) * | 2015-05-06 | 2015-08-12 | 江南大学 | Method for preparing natural hair dye from black plum peels |
| CN108524476B (en) * | 2018-07-09 | 2020-07-24 | 南京农业大学 | Application of xanthohumol in preparation of medicine for resisting porcine epidemic diarrhea virus |
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Non-Patent Citations (3)
| Title |
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| Network pharmacology analyses of the antithrombotic pharmacological mechanism of Fufang Xueshuantong Capsule with experimental support using disseminated intravascular coagulation rats;Shujing Sheng et al.;《Journal of Ethnopharmacology》;20140514;第154卷;第740页For Panax notoginseng部分；第741页For Radix astragali and Radix scrophulariaceae部分；第741页表3；第742页第2段； * |
| Xanthohumol isolated from Humulus lupulus prevents thrombosis without increased bleeding risk by inhibiting platelet activation and mtDNA release;Guang Xin et al;《Free Radical Biology and Medicine》;20170208;第108卷;第247页摘要部分及第251页fig 2. * |
| 复方血栓通胶囊基于血液循环和凝血过程相关靶点的网络药理学研究;刘忠政等;《中山大学学报（自然科学版）》;20130331;第52卷(第2期);第99页讨论部分第2段 * |
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Effective date of registration: 20230703 Address after: 271100 Floor 12, Pharmaceutical Industrial Park, Subdistricts of China, Kou Town, Laiwu District, Jinan, Shandong Patentee after: Shandong peptide Biological Pharmaceutical Co.,Ltd. Address before: No.18 vegetable building, Haoyuan Road, Luocheng street, Shouguang City, Weifang City, Shandong Province 262700 Patentee before: Liu Xiaoshuang |