A swelling and blood stasis resolving granule preparation and a preparation method thereof

Abstract

The application discloses a kind of Xiaozhong Huayu granule preparation and preparation method thereof, belong to the technical field of traditional Chinese medicine preparation.The preparation is made of traditional Chinese medicine extract, soluble starch, dextrin and oligofructose, the traditional Chinese medicine extract is extracted from lecomte, half branch lotus, angelica, red peony root, white peony root, spirea prunifolia, zhebei, oyster, costus, cyperus rotundus, citrus medica, magnolia officinalis, cuttlebone, periostracum cicada, mulberry, shouwufeng, fructus psoraleae, radix pseudostellariae, fried chicken internal gold, ophiopogon and licorice extract.The extract is concentrated and dried, and then mixed with excipient, and then wet granulated with medicinal alcohol, and then the whole granules are obtained.The preparation has the effects of clearing heat and resolving toxicity, promoting blood circulation to remove blood stasis and promoting qi to reduce swelling, and has good storage stability.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a swelling-reducing and blood-stasis-removing granule preparation and its preparation method. Background Technology

[0002] Soft tissue swelling and blood stasis are common clinical conditions, seen in injuries from falls and blows, post-surgical procedures, chronic aseptic inflammation, and peripheral vascular diseases. Persistent swelling not only causes local pain and functional impairment but can also lead to secondary damage such as tissue adhesions and fibrosis, affecting the patient's recovery process.

[0003] Currently, commonly used chemical drugs in clinical practice mainly consist of nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Although they can relieve swelling and pain by inhibiting prostaglandin synthesis or stabilizing lysosomal membranes, long-term or repeated use can lead to adverse reactions such as gastrointestinal mucosal damage, liver and kidney dysfunction, osteoporosis, and immunosuppression. Some patients, especially the elderly and those with chronic diseases, have poor tolerance to these drugs. While diuretics can reduce edema in the short term, they have no direct effect on microcirculatory disturbances and tissue repair caused by blood stasis.

[0004] Traditional Chinese medicine (TCM) theory holds that swelling is closely related to blood stasis. The *Treatise on Blood Disorders* states, "Stasis of blood transforms into water, which also causes edema," and "When blood accumulates for a long time, water will form." The core pathogenesis lies in qi stagnation and blood stasis, heat toxicity accumulation, and water retention, which are mutually causal: impaired qi flow leads to blood stasis; prolonged stasis transforms into heat toxicity; and the accumulation of heat toxicity further aggravates water retention, resulting in a complex interrelationship and mutual influence among these pathological factors, leading to a prolonged and difficult-to-cure condition. Currently available TCM preparations for reducing swelling and removing blood stasis are mostly simple compound formulas, which have the following shortcomings: (1) The efficacy material basis of traditional Chinese medicine compound preparations is not clear enough. Most of them adopt the same water decoction method. The transfer rate of fat-soluble active ingredients such as volatile oils, coumarins and lignans in medicinal materials is low, resulting in large quality fluctuations between batches and unstable efficacy. (2) Medicinal herbs rich in volatile oils, such as Angelica sinensis, Costus root, and Cyperus rotundus, are prone to oxidation and degradation during long-term storage. Traditional decoction methods cannot preserve their volatile active ingredients, and conventional preparation processes result in short shelf life and insufficient stability. (3) Traditional Chinese medicine decoction methods are time-consuming and laborious, inconvenient to carry, and have poor patient compliance. They are especially unsuitable for patients with chronic swelling and blood stasis who need to take medicine for a long time to consolidate the therapeutic effect.

[0005] Therefore, it is necessary to develop a traditional Chinese medicine granule preparation that retains the overall regulatory advantages of traditional Chinese medicine compound prescriptions, meets the quality standards of traditional Chinese medicine preparations, and especially has good long-term storage stability to meet clinical needs. Summary of the Invention

[0006] The purpose of this invention is to provide a granule preparation for reducing swelling and removing blood stasis, and its preparation method. This preparation uses *Hedyotis diffusa* and *Scutellaria barbata* as principal herbs, combined with multiple other medicinal materials. It employs a classified extraction and ethanol wet granulation process. The resulting granule preparation has the effects of clearing heat and detoxifying, promoting blood circulation and removing blood stasis, regulating qi and reducing swelling, and exhibits good long-term storage stability.

[0007] To achieve the above objectives, the present invention provides the following technical solution: A granule preparation for reducing swelling and removing blood stasis includes a traditional Chinese medicine extract, which is obtained by extracting the following raw medicinal materials in parts by weight: 12-18 parts of Hedyotis diffusa, 12-18 parts of Scutellaria barbata, 9-13 parts of Angelica sinensis, 9-13 parts of Paeonia lactiflora, 9-13 parts of Paeonia veitchii, 9-13 parts of Prunella vulgaris, 8-12 parts of Fritillaria thunbergii, 14-20 parts of Ostrea gigas, 5-9 parts of Aucklandia lappa, 5-9 parts of Cyperus rotundus, 5-9 parts of Citronella foenum-graecum, 5-9 parts of Magnolia officinalis, 9-13 parts of Sepia esculenta, 5-9 parts of Cicadae periostracum, 7-11 parts of Morus alba, 7-11 parts of Polygonum multiflorum vine, 3-6 parts of Psoralea corylifolia, 7-11 parts of Codonopsis pilosula, 5-9 parts of stir-fried chicken gizzard lining, 7-11 parts of Ophiopogon japonicus, and 3-6 parts of Glycyrrhiza uralensis.

[0008] Preferably, the raw medicinal materials are expressed in the following weight proportions: 15 parts of white flower snake grass, 15 parts of scutellaria barbata, 10 parts of angelica sinensis, 10 parts of red peony root, 10 parts of white peony root, 10 parts of prunella vulgaris, 9 parts of fritillaria thunbergii, 18 parts of oyster shell, 6 parts of costus root, 6 parts of cyperus rotundus, 6 parts of citron, 6 parts of magnolia officinalis, 10 parts of cuttlebone, 6 parts of cicada molting, 9 parts of mulberry, 9 parts of polygonum multiflorum vine, 4 parts of psoralea corylifolia, 9 parts of codonopsis pilosula, 6 parts of stir-fried chicken gizzard lining, 9 parts of ophiopogon japonicus, and 4 parts of licorice.

[0009] Preferably, the preparation of the traditional Chinese medicine extract includes an alcohol extraction process and a water extraction process, wherein: The raw materials for the alcohol extraction process are Angelica sinensis, Paeonia lactiflora, Paeonia veitchii, Aucklandia lappa, Cyperus rotundus, Citrus medica, Magnolia officinalis, Psoralea corylifolia, and Glycyrrhiza uralensis. The raw materials for the water extraction process are Hedyotis diffusa, Scutellaria barbata, Prunella vulgaris, Fritillaria thunbergii, oyster shell, cuttlebone, cicada molting, mulberry, Polygonum multiflorum vine, Pseudostellaria heterophylla, stir-fried chicken gizzard lining, and Ophiopogon japonicus.

[0010] Preferably, the alcohol extraction process is as follows: extraction with ethanol solution 2 to 4 times, each extraction lasting 1.5 to 2.5 hours, the weight of the ethanol solution being 6 to 10 times the weight of the raw medicinal material in the alcohol extraction process, and the volume concentration of the ethanol solution being 65% to 75%.

[0011] Preferably, the alcohol extraction process is as follows: extraction is performed three times with an ethanol solution, each extraction lasting 2 hours. The weight of the ethanol solution is 8 times the weight of the raw medicinal material in the alcohol extraction process, and the volume concentration of the ethanol solution is 70%.

[0012] Preferably, the water extraction process is as follows: extraction with purified water 2 to 3 times, each extraction lasting 1.5 to 2.5 hours; the weight of purified water is 8 to 12 times the weight of the raw medicinal material in the water extraction process.

[0013] Preferably, oyster and cuttlebone are first crushed into coarse powder, and then decocted for 30 minutes with an appropriate amount of purified water. Then, white flower snake grass, scutellaria barbata, prunella vulgaris, fritillaria thunbergii, cicada molting, mulberry, fleeceflower root vine, codonopsis pilosula, stir-fried chicken gizzard lining, ophiopogon japonicus and the remaining purified water are added and decocted for extraction.

[0014] Preferably, it is made from Chinese herbal extracts, soluble starch, dextrin, and fructooligosaccharides.

[0015] This invention also provides a method for preparing the above-mentioned swelling-reducing and blood-stasis-removing granule preparation, comprising the following steps: S1. Sift the Chinese herbal extract, soluble starch and dextrin, mix them well to obtain a premixed powder; S2. Add fructooligosaccharides to a pharmaceutical ethanol solution, stir to dissolve, and obtain a wetting agent; add the wetting agent to the premixed powder, mix evenly, and prepare a soft pharmaceutical material; S3. The soft drug material is sieved and granulated to obtain wet drug granules, which are then dried and granulated to obtain the final product.

[0016] Furthermore, the proportions of the herbal extract, soluble starch, dextrin, and fructooligosaccharides by weight are as follows: Chinese herbal extracts: 38%–42% Soluble starch 28%–30%, Dextrin 28%–30%, Fructooligosaccharides: 1.8%–2.2%; The sum of the above components is 100%; The mass concentration of the pharmaceutical ethanol solution is 75% to 85%, and the amount used is 8% to 15% of the total weight of the above components.

[0017] Compared with the prior art, the present invention has the following beneficial effects: (1) This formula uses Hedyotis diffusa and Scutellaria barbata as the principal herbs. Swelling and blood stasis are mostly caused by internal heat toxins and stagnation of qi and blood. If the heat toxins are not eliminated, the swelling and pain will not subside, and if the blood stasis is not resolved, new blood will not be generated. Hedyotis diffusa is sweet, bland and cool in nature, and enters the stomach, large intestine and small intestine meridians. It is good at clearing heat and detoxifying, promoting diuresis and reducing swelling, and can make heat toxins go out through urination. Scutellaria barbata is bitter, pungent and cold in nature, and enters the lung, liver and kidney meridians. It is good at clearing heat and detoxifying, dispersing blood stasis and reducing swelling, and can also promote blood circulation to eliminate stagnation. The two herbs complement each other, and the power of clearing heat and detoxifying is doubled. Targeting the pathogenesis of heat toxin stagnation, the swelling can be reduced and the stagnation can be cleared when the heat and toxins are cleared. The treatment method of the whole formula is thus established.

[0018] The formula uses Angelica sinensis, Paeonia lactiflora (red peony root), Paeonia veitchii (white peony root), Prunella vulgaris, Fritillaria thunbergii, and Ostrea gigas as assistant herbs, supporting the principal herbs to invigorate blood circulation, remove blood stasis, soften hardened masses, and dissipate nodules. Among them: Angelica sinensis is sweet, pungent, and warm, entering the liver, heart, and spleen meridians. It nourishes and invigorates blood, regulates menstruation, and relieves pain. The *Jingyue Quanshu* states that it "nourishes while moving, and moves while nourishing," making it an essential medicine for blood-related ailments, removing stagnant blood and generating new blood. Paeonia lactiflora is bitter and slightly cold, entering the liver meridian. It clears heat, cools the blood, disperses blood stasis, and relieves pain, clearing stagnant heat in the blood and removing blood stasis. Paeonia veitchii is bitter, sour, and slightly cold, entering the liver and spleen meridians. It nourishes blood, regulates menstruation, softens the liver, and relieves pain. When Angelica sinensis and Paeonia lactiflora are combined, they nourish and cool the blood, dispersing blood stasis without causing stagnation or depletion. When Paeonia lactiflora and Paeonia veitchii are combined, one disperses and the other astringes, invigorating blood without harming it, and nourishing blood without leaving stasis. The three herbs together invigorate blood, remove blood stasis, nourish blood, and harmonize the body, thus reducing swelling and pain.

[0019] Prunella vulgaris is bitter and cold in nature, entering the liver and gallbladder meridians. It clears liver heat, disperses nodules, and reduces swelling. The Compendium of Materia Medica states that it "relieves internal heat and disperses stagnant qi," and can eliminate scrofula and masses. Fritillaria thunbergii is bitter and cold, entering the lung and heart meridians. It clears heat, resolves phlegm, disperses nodules, and reduces swelling. When combined with Prunella vulgaris, its clearing and dispersing effects are enhanced. Oyster shell is salty, astringent, and slightly cold, entering the liver, gallbladder, and kidney meridians. It softens hardness, disperses nodules, and astringes. Its saltiness softens hardness, its coldness clears heat, and its heavy, sinking nature helps to dissolve tangible lumps. The three herbs combined employ the three methods of clearing the liver, resolving phlegm, and softening hardness simultaneously, thus dissolving the congested lumps.

[0020] The above-mentioned auxiliary herbs are divided into two groups: Angelica sinensis, Paeonia lactiflora, and Paeonia veitchii are mainly used to promote blood circulation and remove blood stasis to treat "stasis"; Prunella vulgaris, Fritillaria thunbergii, and Ostrea gigas are mainly used to soften hardness and dissipate nodules to treat "swelling". The two groups are used in parallel, focusing on the two core aspects of "swelling" and "stasis" in the syndrome of swelling and blood stasis, and assisting the principal herbs to enhance the effect.

[0021] The formula uses costus root, cyperus rhizome, citron, magnolia bark, cuttlebone, cicada slough, mulberry, fleeceflower stem, and psoralea fruit as adjuvant herbs. The purpose of these adjuvant herbs is to assist the principal and assistant herbs in enhancing efficacy and to counteract any imbalances to prevent adverse effects. Among them: Costus root is bitter, pungent, and warm, entering the spleen, stomach, large intestine, and triple burner meridians. It promotes qi circulation, relieves pain, strengthens the spleen, and aids digestion, clearing stagnation of qi in the triple burner. Cyperus rhizome is pungent, slightly bitter, slightly sweet, and neutral, entering the liver, spleen, and triple burner meridians. It soothes the liver, regulates qi, regulates menstruation, and relieves pain. The Compendium of Materia Medica states that it "benefits the triple burner and relieves six stagnations," regulating the body's qi mechanism. Citron is bitter, pungent, sour, and warm, entering the liver, spleen, and lung meridians. It soothes the liver, regulates qi, and resolves phlegm in the middle jiao. Magnolia bark is bitter, pungent, and warm, entering the spleen, stomach, lung, and large intestine meridians. It promotes qi circulation, dries dampness, and eliminates stagnation and fullness. The Records of Famous Physicians states that it "eliminates phlegm and lowers qi." These four qi-regulating herbs work together to soothe the liver, regulate qi to aid blood circulation, and dry dampness to promote qi circulation and reduce swelling, embodying the principle that "when qi flows smoothly, blood flows smoothly, and when qi is smooth, swelling subsides." When qi circulation is smooth, there is no risk of blood stagnation or water retention, thus assisting the blood-activating, stasis-removing, swelling-reducing, and nodule-dispersing herbs in their effects.

[0022] Cuttlebone is salty, astringent, and slightly warm. It enters the spleen and kidney meridians and has the functions of astringing and stopping bleeding, neutralizing acid and relieving pain, and astringing and healing sores. It belongs to the same shellfish category as oyster. When the two are combined, they enhance the ability to soften hardness and disperse nodules. Its astringent and consolidating properties can also restrain other blood-activating and qi-regulating drugs, preventing excessive dispersion from depleting qi and damaging blood.

[0023] Cicada molts are sweet and cold in nature, and enter the lung and liver meridians. They disperse wind-heat and penetrate the meridians. Their bodies are light and float upwards, so they can reach the surface of the head and face, and can also release the stagnant heat hidden in the meridians, so that the evil has a way out.

[0024] Mulberries are sweet, sour, and cold in nature, and enter the heart, liver, and kidney meridians. They nourish yin and replenish blood, generate fluids, and moisten dryness. Polygonum multiflorum vine is sweet and neutral in nature, and enters the heart and liver meridians. It nourishes the heart, calms the mind, dispels wind, and unblocks the meridians. These two herbs nourish yin and replenish blood, firstly to compensate for the lack of new blood generation caused by blood stasis, and secondly to prevent bitter, cold, heat-clearing, qi-regulating, and dampness-drying herbs from damaging yin and depleting blood. This embodies the idea of ​​"treating blood stasis without forgetting to nourish blood."

[0025] Psoralea corylifolia is bitter, pungent, and warm. It enters the kidney and spleen meridians, warms the kidney and assists yang. When combined with a large group of cold and cooling herbs, a small amount of warm herbs are added to achieve the effect of seeking yin within yang, so that the whole formula is cold but not stagnant, clear but not stagnant. This is the method of "counteracting".

[0026] The formula uses Codonopsis pilosula, stir-fried chicken gizzard lining, Ophiopogon japonicus, and licorice as guiding herbs. These guiding herbs direct the herbs to the appropriate meridians and harmonize the effects of the other herbs. Among them: Codonopsis pilosula is sweet, slightly bitter, and neutral in nature. It enters the spleen and lung meridians, invigorates qi and strengthens the spleen, generates fluids and moistens the lungs. It nourishes without causing dryness. In the Qingjie formula, it invigorates qi without generating heat. When combined with Psoralea corylifolia, it invigorates qi and warms yang, replenishes the body's vital energy to help dispel pathogens.

[0027] Stir-fried chicken gizzard is sweet and neutral in nature, and enters the spleen, stomach, small intestine, and bladder meridians. It strengthens the stomach and promotes digestion, eliminates stagnation and dissipates nodules. The "Records of Integrating Chinese and Western Medicine" states that it "is good at resolving tangible stagnation." It can not only help the spleen and stomach to transform and transport nutrients to provide the source of qi and blood, but also assist the principal and assistant herbs in dissipating stagnation.

[0028] Ophiopogon japonicus is sweet, slightly bitter, and slightly cold. It enters the heart, lung, and stomach meridians. It nourishes yin, generates fluids, moistens the lungs, and clears the heart. When used with mulberry and Polygonum multiflorum vine, its yin-nourishing power is enhanced. Moreover, its sweet, cold, and moistening properties can restrain the dryness and scorching nature of the pungent, warm, qi-regulating, and dampness-drying ingredients in the formula.

[0029] Licorice is sweet and neutral in nature, and enters the heart, lung, spleen, and stomach meridians. It tonifies the spleen and replenishes qi, clears heat and detoxifies, relieves spasms and pain, and harmonizes the effects of other herbs. It harmonizes cold and heat, and balances tonification and purgation, so that all the herbs in the formula can function properly without conflicting with each other.

[0030] The formula employs a rigorous combination of principal, assistant, adjuvant, and guiding herbs: the principal herb clears heat and toxins to eliminate the source of the disease; the assistant herbs resolve blood stasis and disperse hard masses to alleviate the main symptoms; the adjuvant herbs regulate qi, nourish yin and blood, and warm yang to assist the principal and assistant herbs in controlling the disease's imbalance; and the guiding herb benefits the spleen and stomach and harmonizes the other herbs to soothe the middle jiao. The combined effects of these herbs encompass clearing heat and detoxifying, promoting blood circulation and removing blood stasis, regulating qi and dispersing stagnation, softening hard masses and reducing swelling, tonifying qi and nourishing yin, and warming yang as a counteracting effect. It combines cold and warm herbs, attack and tonify, and regulates qi and blood simultaneously. It addresses the various pathogenesis factors of swelling and blood stasis syndrome, including heat toxins, blood stasis, qi stagnation, dampness, and yin deficiency, tackling both the root cause and the symptoms. Clearing heat and detoxifying reduces swelling, removing blood stasis and promoting qi circulation stops pain, and restoring blood and yin restores health.

[0031] (2) Based on the polarity and solubility characteristics of the active ingredients of each medicinal material, the 21 medicinal materials were divided into an alcohol extraction group and a water extraction group. Appropriate solvent systems and process parameters were used for extraction to ensure that various active ingredients such as volatile oils, coumarins, lignans, flavonoid glycosides, organic acids, steroidal alkaloids, polysaccharides and trace mineral elements were efficiently transferred, avoiding the low extraction efficiency of fat-soluble components or degradation of active ingredients caused by the traditional compound decoction method.

[0032] The ligustilide and ferulic acid in Angelica sinensis, paeoniflorin and paeoniflorin lactone in Paeonia lactiflora (red and white), costunolide and dehydrocostunolide in Aucklandia lappa, α-cyperone and cyperene in Cyperus rotundus, limonene and citral in Citronella tamariscina, magnolol and honokiol in Magnolia officinalis, psoralen and isopsoralen in Psoralea corylifolia, and glycyrrhizic acid and glycyrrhizin in Glycyrrhiza uralensis are all moderately or weakly polar compounds. They have good solubility and extraction efficiency in ethanol solutions, and ethanol extraction can achieve a high transfer rate of active ingredients. Furthermore, ethanol extraction has a good retention effect on the volatile oil components in the above-mentioned medicinal materials.

[0033] Iridoid glycosides such as cypermethrin and polysaccharides in Hedyotis diffusa, baicalin and polysaccharides in Scutellaria barbata, rosmarinic acid and polysaccharides in Prunella vulgaris, steroidal alkaloids such as fritillary alkaloids A and B in Fritillaria thunbergii, calcium carbonate and various trace elements in oyster and cuttlebone, amino acids and chitin in cicada molting, anthocyanins and polysaccharides in mulberry, stilbene glycosides and polysaccharides in Polygonum multiflorum, polysaccharides and cyclic peptides in Pseudostellaria heterophylla, digestive enzymes such as pepsin and amylase in stir-fried chicken gizzard lining, and saponins and polysaccharides in Ophiopogon japonicus all have good water solubility, and water extraction can effectively extract and retain their activity.

[0034] Among water-extracted medicinal materials, oyster shell and cuttlebone are mineral-based shell medicinal materials with a hard texture, requiring prior processing. First, take the oyster shell and cuttlebone, crush them into coarse powder, add an appropriate amount of purified water, and decoct for 30 minutes. Then add white flower snake grass, scutellaria barbata, prunella vulgaris, fritillaria thunbergii, cicada slough, mulberry, fleeceflower root vine, codonopsis pilosula, stir-fried chicken gizzard lining, and ophiopogon japonicus, and decoct again for extraction to facilitate the full dissolution of minerals, trace elements, and water-soluble active ingredients.

[0035] (3) Using pharmaceutical ethanol solution as a wetting agent for wet granulation, compared with pure water granulation, ethanol solution has a small surface tension, which can wet the powder more evenly, resulting in good particle formation and uniform particle size distribution; ethanol solution has strong volatility and fast drying speed, which reduces the degradation of water-soluble active ingredients during the drying process; the granules prepared by ethanol solution have a dense internal structure and low water content in the finished product, which reduces the hygroscopicity during storage and enhances the long-term stability of the preparation.

[0036] (4) Soluble starch and dextrin are used as composite fillers. The two complement each other in terms of dissolution behavior, so that the granules have good solubility and uniform dispersion when brewed. While playing the role of granulation binder, fructooligosaccharides also utilize their prebiotic properties to regulate intestinal flora, promote the digestive function of the spleen and stomach, and help reduce swelling and remove blood stasis.

[0037] (5) This formula has been used in clinical practice and has shown good swelling and blood stasis reduction effects for patients with traumatic injuries, postoperative swelling, chronic aseptic inflammation and blood stasis syndrome. It can effectively relieve local swelling, pain, ecchymosis and other clinical symptoms. Its safety and effectiveness have been preliminarily verified in clinical practice. Detailed Implementation

[0038] To verify the present invention, the following description is provided in conjunction with embodiments.

[0039] Unless otherwise specified, all raw materials used in the examples are commercially available products. Example 1

[0040] A granule preparation for reducing swelling and removing blood stasis is made from Chinese herbal extracts, soluble starch, dextrin and fructooligosaccharides. By weight percentage, the Chinese herbal extracts account for 40%, the soluble starch accounts for 29%, the dextrin accounts for 29%, and the fructooligosaccharides account for 2%.

[0041] The preparation method of the traditional Chinese medicine extract is as follows: Step 1: Weigh out 10 parts of Angelica sinensis, 10 parts of Paeonia lactiflora, 10 parts of Paeonia veitchii, 6 parts of Aucklandia lappa, 6 parts of Cyperus rotundus, 6 parts of Citrus medica, 6 parts of Magnolia officinalis, 4 parts of Psoralea corylifolia, and 4 parts of Glycyrrhiza uralensis. Crush these ingredients coarsely and place them in extraction container 1. Add 8 times the total weight of the extracted herbs in a 70% (v / v) ethanol solution. Reflux and extract three times, 2 hours each time. Combine the three ethanol extracts and filter through a 200-mesh filter cloth. Concentrate the filtrate under reduced pressure at 65℃ and a vacuum of -0.08 MPa to a relative density of 1.15 to obtain a clear ethanol extract for later use. The relative density was tested at 60℃.

[0042] Step Two: Weigh 18 parts oyster shell and 10 parts cuttlebone, crush them into coarse powder, and put them into extraction container two. Add an appropriate amount of purified water to submerge the herbs and decoct for 30 minutes. Then add 15 parts Oldenlandia diffusa, 15 parts Scutellaria barbata, 10 parts Prunella vulgaris, 9 parts Fritillaria thunbergii, 6 parts Cicadae periostracum, 9 parts Morus alba, 9 parts Polygonum multiflorum vine, 9 parts Codonopsis pilosula, 6 parts stir-fried chicken gizzard lining, and 9 parts Ophiopogon japonicus. Add purified water to 10 times the total weight of all the herbs to be extracted. Decoction and extraction are performed twice, 2 hours each time. Combine the two water extracts, filter through a 200-mesh filter cloth, and concentrate the filtrate under reduced pressure at 70℃ and a vacuum degree of -0.08MPa to a relative density of 1.15 to obtain a clear water extract for later use. The relative density is tested at 60℃.

[0043] Step 3: Combine the above-mentioned alcoholic and water extracts, stir well, and continue to concentrate under reduced pressure at 65℃ and a vacuum of -0.08MPa until the relative density reaches 1.32, obtaining a thick paste. The relative density was tested at 60℃. The thick paste was then vacuum dried at 60℃ and a vacuum of -0.09MPa. After drying, it was pulverized and passed through an 80-mesh sieve to obtain the traditional Chinese medicine extract.

[0044] The preparation method of the swelling-reducing and blood-stasis-removing granules is as follows: S1. Pass the Chinese herbal extract, soluble starch and dextrin through an 80-mesh sieve, put them into a three-dimensional mixer, and mix them at 15 r / min for 25 minutes to obtain a premixed powder.

[0045] S2. Add the fructooligosaccharides to an 80% pharmaceutical ethanol solution and stir until completely dissolved to obtain a wetting agent. While stirring, slowly spray the wetting agent into the premixed powder in a mist until the material can be formed into a ball by hand but crumbles easily when lightly pressed. The amount of pharmaceutical ethanol solution used is 12% of the total weight of the herbal extract, soluble starch, dextrin, and fructooligosaccharides.

[0046] S3. Extrude the soft drug material through a 14-mesh stainless steel sieve to granulate it. Spread the wet granules evenly on a drying tray with a layer thickness not exceeding 1.5cm. Place the tray in a hot air circulating oven and dry at 55℃ until the moisture content does not exceed 5.0%. After drying, granules are sized by passing them through a 14-mesh sieve and then through a 60-mesh sieve to remove fine powder. Collect granules between 14 and 60 mesh.

[0047] S4. The obtained granules are packaged in aluminum foil composite film bags, filled with nitrogen for protection, and sealed to obtain the finished product of swelling-reducing and blood stasis-removing granules. Example 2

[0048] This embodiment provides a granule preparation for reducing swelling and removing blood stasis, which is made from traditional Chinese medicine extract, soluble starch, dextrin and fructooligosaccharides. By weight percentage, the traditional Chinese medicine extract accounts for 38%, the soluble starch accounts for 30%, the dextrin accounts for 30%, and the fructooligosaccharides account for 2%.

[0049] The preparation method of the traditional Chinese medicine extract is as follows: Step 1: Weigh out 9 parts of Angelica sinensis, 9 parts of Paeonia lactiflora, 9 parts of Paeonia veitchii, 5 parts of Aucklandia lappa, 5 parts of Cyperus rotundus, 5 parts of Citrus medica, 5 parts of Magnolia officinalis, 3 parts of Psoralea corylifolia, and 3 parts of Glycyrrhiza uralensis. Crush these ingredients coarsely and place them in extraction container 1. Add 6 times the total weight of the extracted herbs to a 65% (v / v) ethanol solution. Reflux and extract four times, 1.5 hours each time. Combine the four ethanol extracts and filter through a 200-mesh filter cloth. Concentrate the filtrate under reduced pressure at 60℃ and a vacuum of -0.07 MPa to a relative density of 1.12 to obtain a clear ethanol extract for later use. The relative density was tested at 60℃.

[0050] Step Two: Weigh 14 parts oyster shell and 9 parts cuttlebone, crush them into coarse powder, and put them into extraction container two. Add an appropriate amount of purified water to submerge the herbs and decoct for 30 minutes. Then add 12 parts Oldenlandia diffusa, 12 parts Scutellaria barbata, 9 parts Prunella vulgaris, 8 parts Fritillaria thunbergii, 5 parts Cicadae periostracum, 7 parts Morus alba, 7 parts Polygonum multiflorum vine, 7 parts Codonopsis pilosula, 5 parts stir-fried chicken gizzard lining, and 7 parts Ophiopogon japonicus. Add purified water to 8 times the total weight of all the herbs to be extracted. Decoction and extraction are performed 3 times, 1.5 hours each time. Combine the 3 water extracts, filter through a 200-mesh filter cloth, and concentrate the filtrate under reduced pressure at 65℃ and a vacuum degree of -0.07MPa to a relative density of 1.12 to obtain a clear water extract for later use. The relative density is tested at 60℃.

[0051] Step 3: Combine the above-mentioned alcoholic and water extracts, stir well, and continue to concentrate under reduced pressure at 60℃ and a vacuum of -0.08MPa until the relative density reaches 1.30, obtaining a thick paste. The relative density was tested at 60℃. The thick paste was then vacuum dried at 55℃ and a vacuum of -0.09MPa. After drying, it was pulverized and passed through a 70-mesh sieve to obtain the traditional Chinese medicine extract.

[0052] The preparation method of the swelling-reducing and blood-stasis-removing granules is as follows: S1. Pass the Chinese herbal extract, soluble starch and dextrin through a 70-mesh sieve, put them into a V-type mixer, and mix them at 18 r / min for 20 minutes to obtain a premixed powder.

[0053] S2. Add the fructooligosaccharides to a 75% pharmaceutical ethanol solution and stir until completely dissolved to obtain a wetting agent. While stirring, slowly spray the wetting agent into the premixed powder in a mist until the material can be formed into a ball by hand but crumbles easily when lightly pressed. The amount of pharmaceutical ethanol solution used is 8% of the total weight of the herbal extract, soluble starch, dextrin, and fructooligosaccharides.

[0054] S3. Extrude the soft drug material through a 14-mesh stainless steel sieve to granulate it. Spread the wet granules evenly on a drying tray, with a material layer thickness not exceeding 1.5cm. Place it in a hot air circulating oven and dry it at 50℃ until the moisture content does not exceed 5.0%. After drying, granules are sized by passing them through a 14-mesh sieve and then through a 60-mesh sieve to remove fine powder. Collect granules between 14 and 60 mesh.

[0055] S4. The obtained granules are packaged in aluminum foil composite film bags, filled with nitrogen for protection, and sealed to obtain the finished product of swelling-reducing and blood stasis-removing granules. Example 3

[0056] This embodiment provides a granule preparation for reducing swelling and removing blood stasis, which is made from traditional Chinese medicine extract, soluble starch, dextrin and fructooligosaccharides. By weight percentage, the traditional Chinese medicine extract accounts for 42%, the soluble starch accounts for 28%, the dextrin accounts for 28%, and the fructooligosaccharides account for 2%.

[0057] The preparation method of the traditional Chinese medicine extract is as follows: Step 1: Weigh out 13 parts of Angelica sinensis, 13 parts of Paeonia lactiflora, 13 parts of Paeonia veitchii, 9 parts of Aucklandia lappa, 9 parts of Cyperus rotundus, 9 parts of Citrus medica, 9 parts of Magnolia officinalis, 6 parts of Psoralea corylifolia, and 6 parts of Glycyrrhiza uralensis. Crush these ingredients coarsely and place them in extraction container 1. Add 10 times the total weight of the extracted herbs in a 75% (v / v) ethanol solution. Reflux and extract three times, each time for 2.5 hours. Combine the three ethanol extracts and filter through a 200-mesh filter cloth. Concentrate the filtrate under reduced pressure at 65℃ and a vacuum of -0.09 MPa to a relative density of 1.18 to obtain a clear ethanol extract for later use. The relative density was tested at 60℃.

[0058] Step Two: Weigh 20 parts oyster shell and 13 parts cuttlebone, crush them into coarse powder, and put them into extraction container two. Add an appropriate amount of purified water to submerge the herbs and decoct for 30 minutes. Then add 18 parts Oldenlandia diffusa, 18 parts Scutellaria barbata, 13 parts Prunella vulgaris, 12 parts Fritillaria thunbergii, 9 parts Cicadae periostracum, 11 parts Morus alba, 11 parts Polygonum multiflorum vine, 11 parts Codonopsis pilosula, 9 parts stir-fried chicken gizzard lining, and 11 parts Ophiopogon japonicus. Add purified water to 12 times the total weight of all the herbs to be extracted. Decoction and extraction are performed twice, 2.5 hours each time. Combine the two water extracts, filter through a 200-mesh filter cloth, and concentrate the filtrate under reduced pressure at 70℃ and a vacuum degree of -0.09MPa to a relative density of 1.18 to obtain a clear water extract for later use. The relative density is tested at 60℃.

[0059] Step 3: Combine the above-mentioned alcoholic and water extracts, stir well, and continue to concentrate under reduced pressure at 65℃ and a vacuum of -0.08MPa until the relative density reaches 1.35, obtaining a thick paste. The relative density was tested at 60℃. The thick paste was then vacuum dried at 65℃ and a vacuum of -0.09MPa. After drying, it was pulverized and passed through an 80-mesh sieve to obtain the traditional Chinese medicine extract.

[0060] The preparation method of the swelling-reducing and blood-stasis-removing granules is as follows: S1. Pass the Chinese herbal extract, soluble starch and dextrin through an 80-mesh sieve, put them into a three-dimensional mixer, and mix them at 15 r / min for 30 minutes to obtain a premixed powder.

[0061] S2. Add the fructooligosaccharides to an 85% pharmaceutical ethanol solution and stir until completely dissolved to obtain a wetting agent. While stirring, slowly spray the wetting agent into the premixed powder in a mist until the material can be formed into a ball by hand but crumbles easily when lightly pressed. The amount of pharmaceutical ethanol solution used is 15% of the total weight of the herbal extract, soluble starch, dextrin, and fructooligosaccharides.

[0062] S3. Extrude the soft drug material through a 14-mesh stainless steel sieve to granulate it. Spread the wet granules evenly on a drying tray, with a material layer thickness not exceeding 1.5cm. Place it in a hot air circulating oven and dry it at 60℃ until the moisture content does not exceed 5.0%. After drying, granules are sized by passing them through a 14-mesh sieve and then through a 60-mesh sieve to remove fine powder. Collect granules between 14 and 60 mesh.

[0063] S4. The obtained granules are packaged in aluminum foil composite film bags, filled with nitrogen for protection, and sealed to obtain the finished product of swelling-reducing and blood stasis-removing granules.

[0064] The swelling-reducing and blood-stasis-removing granules prepared in Example 1 were placed at room temperature and protected from light, and sealed in an aluminum foil composite film bag. Samples were taken at 0, 1, 3, 6, 12, 18 and 24 months, and tested according to the following items. The results are shown in Table 1.

[0065] Characteristics: Take an appropriate amount of sample, place it in a white porcelain dish, and observe the color, shape, and odor of the particles under natural light.

[0066] Solubility: Take 5g of sample, place it in a 250mL beaker, add 200mL of 80℃ hot water, stir for 5 minutes, and observe whether the particles are completely dissolved and whether there are any charred residues or foreign objects.

[0067] Moisture content: Take about 2g of sample and place it in a weighing bottle that has been pre-weighed. Dry it in an oven at 105℃ until it reaches constant weight. Calculate the moisture content using the following formula: Moisture (%) = (Weight before drying - Weight after drying) / Weight before drying × 100%.

[0068] Table 1 Stability test results time Properties Solubility Moisture (%) October Brownish-brown granules with a slightly fragrant aroma Completely melted, with no charred residue or foreign matter. 3.4 January Brownish-brown granules with a slightly fragrant aroma Completely melted, with no charred residue or foreign matter. 3.4 March Brownish-brown granules with a slightly fragrant aroma Completely melted, with no charred residue or foreign matter. 3.5 June Brownish-brown granules with a slightly fragrant aroma Completely melted, with no charred residue or foreign matter. 3.6 December Brownish-brown granules with a slightly fragrant aroma Completely melted, with no charred residue or foreign matter. 3.8 18 months Brownish-brown granules with a slightly fragrant aroma Completely melted, with no charred residue or foreign matter. 4.0 24 months Brownish-brown granules with a slightly fragrant aroma Completely melted, with no charred residue or foreign matter. 4.2 As shown in Table 1, after being sealed and stored at room temperature in the dark for 24 months, the properties and solubility of the particles did not change significantly, and the moisture content remained below 5.0%, indicating that the product has good stability under normal storage conditions.

[0069] To verify the clinical efficacy of the preparation of this invention, outpatient cases of soft tissue swelling and blood stasis syndrome who had used the formula were collected and analyzed.

[0070] Inclusion criteria for cases: patients with a clear history of sprains, post-surgical or chronic aseptic inflammation, accompanied by clinical manifestations such as local swelling, pain or ecchymosis, who have taken this product granules continuously for no less than 2 weeks, and who have not taken other anti-swelling and ecchymosis-removing drugs during the medication period.

[0071] Exclusion criteria: Patients with fractures requiring surgical fixation; patients with severe heart, liver, or kidney dysfunction; pregnant or lactating women; patients with known hypersensitivity to any component of this product.

[0072] A total of 40 cases meeting the inclusion criteria were collected, including 23 males and 17 females; aged 21 to 68 years, with an average age of 43.5 years; with a course of illness ranging from 1 day to 3 months; among them, 18 cases were traumatic injuries, 12 cases were postoperative swelling, and 10 cases were chronic aseptic inflammation.

[0073] The patient should take 10g of this product in granules twice daily, dissolved in warm water, for 2-4 weeks. During the medication period, the patient should maintain a normal diet and not use other anti-inflammatory or analgesic medications concurrently.

[0074] Observation indicators: Based on the patient's outpatient records before and after treatment, record the difference in swelling circumference of the affected area (the difference in circumference between the affected limb and the healthy limb at the same location), pain visual analog scale score, and changes in ecchymosis area.

[0075] Refer to the relevant efficacy evaluation criteria in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines": Significant effect: swelling circumference difference reduced by ≥70%, pain score decreased by ≥70%, and ecchymosis area reduced by ≥70%.

[0076] Effective: The difference in swelling circumference is reduced by 30% to 69%, the pain score decreases by 30% to 69%, and the area of ​​ecchymosis is reduced by 30% to 69%.

[0077] Invalid: The above standards were not met.

[0078] Changes in indicators before and after treatment: Table 2 shows the changes in swelling circumference, pain score and ecchymosis area before and after treatment in 40 patients.

[0079] Table 2. Changes in observed indicators before and after treatment (x±s) time Number of examples Difference in swelling circumference (cm) Pain VAS score Area of ​​ecchymosis (cm²) Before treatment 40 3.5±1.3 5.8±1.4 18.7±8.4 After treatment 40 1.0±0.6 1.5±0.9 4.2±3.6 As shown in Table 2, the swelling circumference difference, pain score and ecchymosis area of ​​the patients were significantly reduced after treatment compared with before treatment.

[0080] Overall efficacy: Among the 40 patients, 18 cases showed significant improvement (45.0%), 19 cases showed improvement (47.5%), and 3 cases showed no improvement (7.5%), with an overall effective rate of 92.5%.

[0081] Symptom improvement: Among the 40 patients, 40 had local pain, and 37 of them were relieved after treatment; 40 had swelling, and 37 of them subsided after treatment; 28 had ecchymosis, and 24 of them subsided or significantly improved after treatment; and 22 had functional impairment, and 19 of them improved after treatment.

[0082] Adverse reactions: No obvious gastrointestinal discomfort, rash or other adverse reactions were observed in any of the 40 patients during the medication period, and no abnormalities were found in blood routine and liver and kidney function tests.

[0083] The above clinical observation results show that the swelling-reducing and blood-stasis-removing granules of the present invention have a good swelling-reducing and blood-stasis-removing effect on patients with soft tissue swelling and blood stasis syndrome. They can effectively relieve clinical symptoms such as local swelling, pain, ecchymosis and functional impairment, and have good safety.

[0084] The above description is only a preferred embodiment of the present invention and does not limit the scope of protection of the present invention. Any equivalent structural or procedural transformations made based on the content of the present invention specification, or direct or indirect applications in other related technical fields, are similarly included within the scope of protection of the present invention.

Claims

1. A granule preparation for reducing swelling and removing blood stasis, comprising extracts of traditional Chinese medicine, characterized in that, The herbal extract is obtained from the following raw medicinal materials in parts by weight: 12-18 parts of Hedyotis diffusa, 12-18 parts of Scutellaria barbata, 9-13 parts of Angelica sinensis, 9-13 parts of Paeonia lactiflora, 9-13 parts of Paeonia veitchii, 9-13 parts of Prunella vulgaris, 8-12 parts of Fritillaria thunbergii, 14-20 parts of Ostrea gigas, 5-9 parts of Aucklandia lappa, 5-9 parts of Cyperus rotundus, 5-9 parts of Citronella foenum-graecum, 5-9 parts of Magnolia officinalis, 9-13 parts of Sepia esculenta, 5-9 parts of Cicadae periostracum, 7-11 parts of Morus alba, 7-11 parts of Polygonum multiflorum vine, 3-6 parts of Psoralea corylifolia, 7-11 parts of Codonopsis pilosula, 5-9 parts of stir-fried chicken gizzard lining, 7-11 parts of Ophiopogon japonicus, and 3-6 parts of Glycyrrhiza uralensis.

2. The swelling-reducing and blood-stasis-removing granule preparation according to claim 1, characterized in that, The weight parts of the raw medicinal materials are as follows: 15 parts of white flower snake grass, 15 parts of scutellaria barbata, 10 parts of angelica sinensis, 10 parts of red peony root, 10 parts of white peony root, 10 parts of prunella vulgaris, 9 parts of fritillaria thunbergii, 18 parts of oyster shell, 6 parts of costus root, 6 parts of cyperus rotundus, 6 parts of citron, 6 parts of magnolia officinalis, 10 parts of cuttlebone, 6 parts of cicada molting, 9 parts of mulberry, 9 parts of polygonum multiflorum vine, 4 parts of psoralea corylifolia, 9 parts of codonopsis pilosula, 6 parts of stir-fried chicken gizzard lining, 9 parts of ophiopogon japonicus, and 4 parts of licorice.

3. The swelling-reducing and blood-stasis-removing granule preparation according to claim 1 or 2, characterized in that, The preparation of the herbal extract includes alcohol extraction and water extraction, wherein: The raw materials for the alcohol extraction process are Angelica sinensis, Paeonia lactiflora, Paeonia veitchii, Aucklandia lappa, Cyperus rotundus, Citrus medica, Magnolia officinalis, Psoralea corylifolia, and Glycyrrhiza uralensis. The raw materials for the water extraction process are Hedyotis diffusa, Scutellaria barbata, Prunella vulgaris, Fritillaria thunbergii, oyster shell, cuttlebone, cicada molting, mulberry, Polygonum multiflorum vine, Pseudostellaria heterophylla, stir-fried chicken gizzard lining, and Ophiopogon japonicus.

4. The swelling-reducing and blood-stasis-removing granule preparation according to claim 3, characterized in that, The alcohol extraction process is as follows: 2 to 4 extractions with ethanol solution, each extraction lasting 1.5 to 2.5 hours, the weight of the ethanol solution being 6 to 10 times the weight of the raw medicinal material in the alcohol extraction process, and the volume concentration of the ethanol solution being 65% to 75%.

5. The swelling-reducing and blood-stasis-removing granule preparation according to claim 4, characterized in that, The alcohol extraction process is as follows: the ethanol solution is used for extraction three times, each extraction lasting 2 hours. The weight of the ethanol solution is 8 times the weight of the raw medicinal material in the alcohol extraction process, and the volume concentration of the ethanol solution is 70%.

6. The swelling-reducing and blood-stasis-removing granule preparation according to claim 3, characterized in that, The water extraction process is as follows: extract with purified water 2 to 3 times, each extraction lasting 1.5 to 2.5 hours; the weight of purified water is 8 to 12 times the weight of the raw medicinal material in the water extraction process.

7. The swelling-reducing and blood-stasis-removing granule preparation according to claim 3, characterized in that, in, First, take oyster and cuttlefish bone, crush them into coarse powder, add an appropriate amount of purified water and decoct for 30 minutes. Then add white flower snake grass, scutellaria barbata, prunella vulgaris, fritillaria thunbergii, cicada molting, mulberry, fleeceflower root vine, codonopsis pilosula, stir-fried chicken gizzard lining, ophiopogon japonicus and the remaining purified water, and decoct to extract.

8. The swelling-reducing and blood-stasis-removing granule preparation according to claim 1 or 2, characterized in that, It is made from extracts of traditional Chinese medicine, soluble starch, dextrin, and fructooligosaccharides.

9. A method for preparing the swelling-reducing and blood-stasis-removing granule preparation as described in claim 1, characterized in that, Includes the following steps: S1. Sift the Chinese herbal extract, soluble starch and dextrin, mix them well to obtain a premixed powder; S2. Add fructooligosaccharides to a pharmaceutical ethanol solution, stir to dissolve, and obtain a wetting agent; add the wetting agent to the premixed powder, mix evenly, and prepare a soft pharmaceutical material; S3. The soft drug material is sieved and granulated to obtain wet drug granules, which are then dried and granulated to obtain the final product.

10. The method for preparing the swelling-reducing and blood-stasis-removing granule preparation according to claim 9, characterized in that, The proportions of the herbal extract, soluble starch, dextrin, and fructooligosaccharides by weight are as follows: Chinese herbal extracts: 38%–42% Soluble starch 28%–30%, Dextrin 28%–30%, Fructooligosaccharides: 1.8%–2.2%; The sum of the above components is 100%; The mass concentration of the pharmaceutical ethanol solution is 75% to 85%, and the amount used is 8% to 15% of the total weight of the above components.