阅读说明：本技术 一种防治下肢深静脉血栓后遗症期的药物组合物及其制备方法和用途 (Pharmaceutical composition for preventing and treating sequela of deep venous thrombosis of lower limbs and preparation method and application thereof ) 是由 李霞 黄玉霞 喻杉 冯光富 张忠 于 2020-05-26 设计创作，主要内容包括：本发明提供了一种防治下肢深静脉血栓后遗症期的药物组合物及其制备方法和用途,属于中药领域。该药物组合物是由如下重量配比的原料药制备而成的制剂：黄芪30～50份,桃仁5～20份,红花5～20份,川芎10～20份,当归尾10～20份,赤芍10～20份,益母草20～40份,茯苓10～30份,牡丹皮10～20份,丹参10～30份,威灵仙10～20份,羌活5～10份,水蛭1～10份,三七1～10份,党参10～30份,白术10～20份。该组合物各药物配伍精当,能够益气活血、通利脉道,可有效治疗下肢深静脉血栓后遗症期,效果与临床上常用的西药利伐沙班相当,且费用更为低廉；同时该组合物对肝肾损伤小,不良反应发生率低,可用于长期治疗。本发明采用丸剂制备,煎煮及携带更便利,有利于长期服用,且丸剂性质更为平和,安全性更佳。(The invention provides a pharmaceutical composition for preventing and treating sequelae of deep venous thrombosis of lower limbs, a preparation method and application thereof, belonging to the field of traditional Chinese medicines. The pharmaceutical composition is a preparation prepared from the following raw materials in parts by weight: 30-50 parts of astragalus membranaceus, 5-20 parts of peach kernels, 5-20 parts of safflower carthamus, 10-20 parts of ligusticum wallichii, 10-20 parts of angelica tails, 10-20 parts of red peony roots, 20-40 parts of motherwort, 10-30 parts of poria cocos, 10-20 parts of moutan barks, 10-30 parts of salvia miltiorrhiza, 10-20 parts of radix clematidis, 5-10 parts of notopterygium roots, 1-10 parts of leeches, 1-10 parts of pseudo-ginseng, 10-30 parts of codonopsis pilosula and 10-20 parts of bighead atractylodes rhizome. The composition has the advantages of precise and appropriate compatibility of medicines, capabilities of tonifying qi and activating blood circulation and promoting blood circulation, capability of effectively treating sequelae of deep venous thrombosis of lower limbs, equivalent effect to that of a clinically common western medicine rivaroxaban, and lower cost; meanwhile, the composition has small damage to liver and kidney and low incidence of adverse reaction, and can be used for long-term treatment. The invention is prepared by pills, is more convenient to decoct and carry, is beneficial to long-term taking, and has milder pill property and better safety.)

1. A pharmaceutical composition for preventing and treating sequela of deep venous thrombosis of lower limbs is characterized in that: the preparation is prepared from the following raw material medicines in parts by weight: 30-50 parts of astragalus membranaceus, 5-20 parts of peach kernels, 5-20 parts of safflower carthamus, 10-20 parts of ligusticum wallichii, 10-20 parts of angelica tails, 10-20 parts of red peony roots, 20-40 parts of motherwort, 10-30 parts of poria cocos, 10-20 parts of moutan barks, 10-30 parts of salvia miltiorrhiza, 10-20 parts of radix clematidis, 5-10 parts of notopterygium roots, 1-10 parts of leeches, 1-10 parts of pseudo-ginseng, 10-30 parts of codonopsis pilosula and 10-20 parts of bighead atractylodes rhizome.

2. The pharmaceutical composition of claim 1, wherein: the preparation is prepared from the following raw material medicines in parts by weight: 30-50 parts of astragalus membranaceus, 9-20 parts of peach kernels, 9-20 parts of safflower carthamus, 10-20 parts of ligusticum wallichii, 10-20 parts of angelica tails, 10-20 parts of red peony roots, 20-40 parts of motherwort, 12-30 parts of poria cocos, 12-20 parts of moutan barks, 15-30 parts of salvia miltiorrhiza, 10-15 parts of radix clematidis, 5-10 parts of notopterygium roots, 1-5 parts of leeches, 5-10 parts of pseudo-ginseng, 15-30 parts of codonopsis pilosula and 10-20 parts of bighead atractylodes rhizome.

3. The pharmaceutical composition of claim 2, wherein: the preparation is prepared from the following raw material medicines in parts by weight: 40 parts of astragalus membranaceus, 10 parts of peach kernel, 10 parts of safflower, 12 parts of ligusticum wallichii, 12 parts of angelica tail, 15 parts of red paeony root, 30 parts of motherwort, 15 parts of poria cocos, 15 parts of moutan bark, 20 parts of salvia miltiorrhiza, 10 parts of radix clematidis, 6 parts of notopterygium root, 3 parts of leech, 6 parts of pseudo-ginseng, 20 parts of codonopsis pilosula and 15 parts of bighead atractylodes rhizome.

4. The pharmaceutical composition according to any one of claims 1 to 3, wherein: the preparation is prepared by mixing crude drug powder of raw drug materials, water or organic solvent extract according to weight ratio and adding pharmaceutically acceptable auxiliary materials or auxiliary components.

5. The pharmaceutical composition of claim 4, wherein: the preparation is an oral preparation;

preferably, the oral preparation is decoction, powder, pills, tablets, granules and capsules.

6. The pharmaceutical composition of claim 5, wherein: the oral preparation is a pill;

preferably, the pill is a honeyed pill.

7. A method of preparing a pharmaceutical composition according to any one of claims 1 to 6, wherein: it comprises the following steps:

directly pulverizing the raw materials in weight ratio, or extracting with water or organic solvent, and adding pharmaceutically acceptable adjuvants or auxiliary components.

8. The method of claim 7, wherein: it comprises the following steps: and taking the raw material medicines according to the weight ratio, adding drinking water, decocting for 1-3 times, filtering, and combining the filtrates to obtain the traditional Chinese medicine.

9. The method of claim 7, wherein: it comprises the following steps: taking the raw materials in weight ratio, drying and crushing at low temperature, and adding honey to prepare honeyed pills;

preferably, the powder is dried and crushed at low temperature and then passes through a 100-mesh sieve;

and/or the water content of the honey is 14-16%, and the relative density is 1.37-1.40;

more preferably, the mass ratio of the bulk drugs to the honey is 1: 1.

10. Use of the pharmaceutical composition of any one of claims 1 to 6 for the preparation of a medicament for preventing and treating sequelae of deep venous thrombosis of lower limbs;

preferably, the drug is a drug for reducing the number of thrombi;

and/or, the medicament is a medicament for treating local pruritus, swelling and pain.

Technical Field

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a pharmaceutical composition for preventing and treating sequelae of deep venous thrombosis of lower limbs, and a preparation method and application thereof.

Background

The lower Limb Deep Venous Thrombosis (LDVT) is a common clinical disease, belongs to the field of 'femoral swelling' in traditional Chinese medicine, and is common inducing factors such as major operation, trauma, long-term bed rest, limb braking and the like, so that pulmonary artery embolism and post-thrombosis syndrome can be caused, the life quality of a patient is seriously affected, and even death can be caused. The disease is divided into an acute stage (within 14 days), a prolonged stage (14 days to 3 months) and a sequela stage (after 3 months). The treatment for the disease is mainly focused on the acute stage and the delayed stage at present, and the attention to the sequela stage is less.

The sequela stage of deep venous thrombosis of the lower limb is also called post-deep venous thrombosis syndrome (PTS), which is a quite complex pathophysiological process that after deep venous thrombosis of the lower limb, the lower limb is not treated in time or is not treated completely, thrombus is repaired by organization, canalization and intimation, and chronic lesion remained after blockage, incomplete recanalization or complete recanalization is also called chronic lower limb venous obstruction. In the first 2 years of diagnosis as LDVT, even through standardized anticoagulation treatment, 20-50% of patients develop PTS, once the patients enter sequela stage, the guidelines recommend long-term administration or even lifelong administration of anticoagulation drugs, but the traditional anticoagulation drug warfarin has higher bleeding risk in long-term treatment and needs to closely monitor coagulation indexes; while NOAC medicines such as rivaroxaban, dabigatran, apixaban and the like reduce the pain of frequent blood drawing and reduce the risk of bleeding, the novel anticoagulant drug is expensive, mainly through renal metabolism, the risk of liver and kidney function damage is difficult to avoid after long-term administration, and especially for the old and people with abnormal kidney function, the novel anticoagulant drug is not favorable for long-term anticoagulation thrombolysis.

The single medicine or compound traditional Chinese medicine has definite curative effect on anticoagulation and low cost, but the currently reported experimental formula mainly has the functions of promoting blood circulation and removing blood stasis and clearing heat and eliminating dampness, has certain curative effect, but neglects the treatment of the etiology. The single application of attack method aiming at middle-aged and old people, weak and long-time bedridden patients, orthopedic trauma braking and orthopedic major surgery patients may further consume qi and yin, cause the stagnation of the pulse channel and slow blood circulation, increase the risk of lower limb deep vein thrombosis, and use too much cold and cool medicines, have the suspicion of blood stasis, obviously cannot be suitable for the long-term administration of patients with thrombus. Patent CN105267535 discloses a medicine for preventing and treating postoperative lower limb deep vein thrombosis, which is prepared from leech, caulis spatholobi, salvia miltiorrhiza, radix achyranthis bidentatae, dragon's blood, pseudo-ginseng powder, peach kernel, safflower, prepared rehmannia root, ligusticum wallichii, red peony root, angelica tail, astragalus, fried bighead atractylodes rhizome, poria cocos, codonopsis pilosula, coptis chinensis, phellodendron, rhizoma atractylodis, honeysuckle, pawpaw and raw liquorice; wherein Hirudo is monarch drug, and Saviae Miltiorrhizae radix, Achyranthis radix, sanguis Draxonis, Notoginseng radix powder, radix Angelicae sinensis tail, semen Persicae, Carthami flos, radix rehmanniae Preparata, rhizoma Ligustici Chuanxiong, radix Paeoniae Rubra, and caulis Spatholobi are ministerial drugs. Although the formula has the effects of benefiting qi and activating blood circulation, the formula has the main effects of preventing postoperative deep venous thrombosis of lower limbs and has no application support in the sequela stage of the deep venous thrombosis of the lower limbs; meanwhile, in terms of compatibility, the traditional Chinese medicine composition is matched with heat-clearing and dampness-removing medicines such as coptis chinensis, phellodendron, honeysuckle and pawpaw, occupies a certain proportion in the original formula, has slightly cold and cool medicinal properties, is more suitable for patients with qi deficiency and blood stasis and damp-heat, and is not completely suitable for all patients with thrombus.

The pharmaceutical composition has good effect of preventing and treating the LDVT sequelae, small side effect and substantial price, and is suitable for long-term administration.

Disclosure of Invention

The invention aims to provide a pharmaceutical composition for preventing and treating sequelae of deep venous thrombosis of lower limbs, a preparation method and application thereof.

The invention provides a pharmaceutical composition for preventing and treating sequelae of deep venous thrombosis of lower limbs, which is a preparation prepared from the following raw material medicines in parts by weight: 30-50 parts of astragalus membranaceus, 5-20 parts of peach kernels, 5-20 parts of safflower carthamus, 10-20 parts of ligusticum wallichii, 10-20 parts of angelica tails, 10-20 parts of red peony roots, 20-40 parts of motherwort, 10-30 parts of poria cocos, 10-20 parts of moutan barks, 10-30 parts of salvia miltiorrhiza, 10-20 parts of radix clematidis, 5-10 parts of notopterygium roots, 1-10 parts of leeches, 1-10 parts of pseudo-ginseng, 10-30 parts of codonopsis pilosula and 10-20 parts of bighead atractylodes rhizome.

Further, the pharmaceutical composition is a preparation prepared from the following raw material medicines in parts by weight: 30-50 parts of astragalus membranaceus, 9-20 parts of peach kernels, 9-20 parts of safflower carthamus, 10-20 parts of ligusticum wallichii, 10-20 parts of angelica tails, 10-20 parts of red peony roots, 20-40 parts of motherwort, 12-30 parts of poria cocos, 12-20 parts of moutan barks, 15-30 parts of salvia miltiorrhiza, 10-15 parts of radix clematidis, 5-10 parts of notopterygium roots, 1-5 parts of leeches, 5-10 parts of pseudo-ginseng, 15-30 parts of codonopsis pilosula and 10-20 parts of bighead atractylodes rhizome.

Further, the pharmaceutical composition is a preparation prepared from the following raw material medicines in parts by weight: 40 parts of astragalus membranaceus, 10 parts of peach kernel, 10 parts of safflower, 12 parts of ligusticum wallichii, 12 parts of angelica tail, 15 parts of red paeony root, 30 parts of motherwort, 15 parts of poria cocos, 15 parts of moutan bark, 20 parts of salvia miltiorrhiza, 10 parts of radix clematidis, 6 parts of notopterygium root, 3 parts of leech, 6 parts of pseudo-ginseng, 20 parts of codonopsis pilosula and 15 parts of bighead atractylodes rhizome.

Furthermore, the pharmaceutical composition is a preparation prepared by adding pharmaceutically acceptable auxiliary materials or auxiliary components into crude drug powder, water or organic solvent extract of the raw drug materials according to the weight ratio.

Further, the formulation is an oral formulation;

preferably, the oral preparation is decoction, powder, pills, tablets, granules and capsules.

Further, the oral formulation is a pill;

preferably, the pill is a honeyed pill.

The invention also provides a preparation method of the pharmaceutical composition, which comprises the following steps:

directly pulverizing the raw materials in weight ratio, or extracting with water or organic solvent, and adding pharmaceutically acceptable adjuvants or auxiliary components.

Further, the preparation method comprises the following steps: and taking the raw material medicines according to the weight ratio, adding drinking water, decocting for 1-3 times, filtering, and combining the filtrates to obtain the traditional Chinese medicine.

Further, the preparation method comprises the following steps: taking the raw materials in weight ratio, drying and crushing at low temperature, and adding honey to prepare honeyed pills;

preferably, the powder is dried and crushed at low temperature and then passes through a 100-mesh sieve;

and/or the water content of the honey is 14-16%, and the relative density is 1.37-1.40;

more preferably, the mass ratio of the bulk drugs to the honey is 1: 1.

The invention also provides the application of the pharmaceutical composition in preparing the drugs for preventing and treating sequelae of deep venous thrombosis of lower limbs;

preferably, the drug is a drug for reducing the number of thrombi;

and/or, the medicament is a medicament for treating local pruritus, swelling and pain.

The pharmaceutical composition is prepared from astragalus, peach kernel, safflower, ligusticum wallichii, angelica tail, red paeony root, motherwort herb, tuckahoe, tree peony bark, salvia miltiorrhiza, leech, pseudo-ginseng, clematis chinensis, notopterygium root, codonopsis pilosula and bighead atractylodes rhizome. The radix Angelicae sinensis tail is the tail of Chinese medicinal radix Angelicae sinensis.

The formula mainly comprises astragalus and codonopsis pilosula, is sweet and warm in nature, can tonify primordial qi, and is a monarch drug in the formula, aiming at promoting blood circulation when qi is strong and removing blood stasis and dredging collaterals when blood is circulated. The angelica tail can promote blood circulation and remove meridian obstruction without damaging blood, and the salvia miltiorrhiza can promote blood circulation and regulate menstruation, nourish blood and remove stasis, and dredge and seal vessels, and is used as a ministerial drug. Radix paeoniae rubrathe, peach kernel, safflower, bark of peony root, notoginseng, angelica root and root of red rooted saliva, all of which are used as adjuvant drugs for promoting blood circulation and removing blood stasis; the ligusticum wallichii is good at promoting blood circulation and nourishing blood, is a blood-qi-tonifying medicine, is pungent and warm in property and strong in nature, can pass through twelve meridians to dredge channels and collaterals, is good at removing long-term accumulation, nodule and qi block, and the notopterygium root is pungent, bitter and warm in property, mainly carries the prevalence of blood vessels, belongs to wind medicine, is pungent and mild in nature and can be used for promoting blood circulation and removing blood stasis by warming and dredging, and has no disadvantage of stasis retention, and the leech is specially and well taken to exert the force of promoting blood circulation and removing blood stasis, has the function of promoting water passage, is used for circulating the whole body and has the efficacy of medicine application. The bighead atractylodes rhizome is an essential medicine for strengthening the spleen and stomach, and the traditional Chinese medicine has the functions of tonifying spleen and qi, promoting diuresis and eliminating dampness and regulating qi and middle warmer; poria has effects in promoting diuresis, eliminating phlegm, tonifying, invigorating spleen, and eliminating dampness; motherwort herb can dispel wind and clear heat, and remove dampness to alleviate pain, and it is also an adjuvant drug for swelling and pain due to deficiency heat and damp-toxicity recorded in Benjing. The whole formula is combined, the qi tonifying medicine and the blood activating medicine are compatible, so that the effects of invigorating qi and promoting blood circulation are achieved to treat the root cause, the effects of removing blood stasis and dredging collaterals are achieved to treat the symptoms, and the root cause and symptoms are considered; moreover, when used together, the herbs can tonify qi without stagnation and activate blood without damaging healthy qi, so that the symptoms of qi are cured.

The pharmaceutical composition has precise and appropriate compatibility of medicines, can tonify qi, activate blood, promote blood circulation and promote blood circulation, can effectively treat sequela of deep venous thrombosis of lower limbs, has the effect equivalent to that of a clinically common western medicine rivaroxaban, and has lower cost; meanwhile, the pharmaceutical composition has small damage to kidney function and low bleeding risk, and can be used for long-term treatment. The invention is prepared by pills, which not only avoids the defects of inconvenient decoction and carrying of traditional Chinese medicines and is beneficial to long-term administration, but also has milder pill property and better safety.

Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.

The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.

Detailed Description

The raw materials and equipment used in the embodiment of the present invention are known products and obtained by purchasing commercially available products.