Hippophae rhamnoides compound composition, hippophae rhamnoides compound active component, hippophae rhamnoides compound preparation, and preparation method and application thereof

Abstract

This invention discloses a sea buckthorn compound composition, sea buckthorn compound active ingredients, sea buckthorn compound preparations, their preparation methods, and applications. The sea buckthorn compound composition, by weight, comprises the following components: 20-26 parts sea buckthorn, 17-21 parts kelp, 9-11 parts chuanxiong rhizome, 9-11 parts astragalus root, 9-11 parts notoginseng, 7-9 parts earthworm, 7-9 parts scutellaria baicalensis, 7-9 parts cassia seed, 3-5 parts hawthorn, and 3-5 parts chrysanthemum. The sea buckthorn compound active ingredients and sea buckthorn compound preparations obtained from the sea buckthorn compound composition of this invention exhibit excellent stability and pharmacodynamic properties, can improve vascular condition or blood lipid levels, and are suitable for treating various diseases related to arterial plaque, dyslipidemia, vascular wall thickening, or vascular endothelial inflammation.

Description

Technical Field

[0001] This invention relates to a sea buckthorn compound composition, sea buckthorn compound active ingredients, sea buckthorn compound preparations, their preparation methods and applications. Background Technology

[0002] In traditional Chinese medicine, the formation and progression of atherosclerotic (AS) plaques can be summarized as the combination of four factors: phlegm, blood stasis, toxins, and deficiency. Spleen deficiency leads to impaired transport and transformation, resulting in the internal generation of phlegm and turbidity. This is caused by excessive consumption of rich and sweet foods or by spleen deficiency due to old age, which prevents the transformation of food into essential nutrients and produces fat (equivalent to lipid metabolism disorder in modern medicine). Phlegm and turbidity then flow into the blood vessels along with the qi and blood. Qi stagnation and blood stasis, phlegm and blood stasis intertwined—Qi deficiency or stagnation leads to poor blood circulation and the internal generation of blood stasis. Phlegm and blood stasis intertwine and adhere to the vessel walls, gradually forming tangible masses (i.e., plaques); Toxins damage blood vessels and cause plaques to become unstable—Prolonged accumulation of phlegm and blood stasis can lead to heat and toxins (oxidized low-density lipoprotein, inflammatory factors, etc.), which damage the vascular endothelium, making plaques prone to rupture and triggering cardiovascular and cerebrovascular events. When the body's vital energy is deficient, the root of the disease is difficult to eradicate—prolonged illness depletes vital energy, gradually weakening the spleen and kidneys, making them unable to transform phlegm and blood stasis, and plaques become difficult to reverse.

[0003] Commonly used clinical Chinese medicine combinations include Compound Danshen Dripping Pills, Quick-Acting Heart-Saving Pills, Tongxinluo Capsules, and Musk Heart-Protecting Pills. These combinations are effective in improving angina pectoris, myocardial ischemia, microcirculation, and in anti-inflammatory, antioxidant, and anti-platelet aggregation effects.

[0004] However, most traditional Chinese medicine formulas focus solely on promoting blood circulation and removing blood stasis, failing to adequately address complex syndromes such as "qi deficiency and blood stasis, phlegm and blood stasis, qi and yin deficiency, and yang deficiency and cold coagulation." Some formulas lack clear coordination of principal, assistant, and adjuvant herbs, failing to address the core pathogenesis of "heart vessel obstruction and heart qi deficiency," resulting in weak ability to treat both the root cause and symptoms, regulate qi and blood, and treat phlegm and blood stasis simultaneously. Furthermore, they lack sufficient intervention in modern pathological processes such as atherosclerosis, dyslipidemia, and inflammatory responses. Traditional preparations (tablets, capsules, oral liquids) dissolve slowly, have poor absorption, and take a long time to reach peak blood concentration, making it difficult to quickly relieve acute angina pectoris and improve myocardial ischemia. Compared to Western medicines like nitroglycerin, they have significantly lower speed and emergency efficacy, and are mostly used as adjunctive therapy during stable periods, with limited efficacy when used alone during acute phases. Some traditional Chinese medicine combinations also contain ingredients such as borneol, toad venom, and leeches, which can easily cause gastrointestinal irritation (nausea, bloating, diarrhea), allergies, and numbness of the mouth and tongue.

[0005] In summary, existing traditional Chinese medicine compositions for treating atherosclerosis and related conditions suffer from defects such as poor compatibility, slow onset of action, and poor safety and compliance. These deficiencies make it difficult to meet the modern clinical demand for efficient, rapid, safe, stable, precise, and comprehensive intervention. There is an urgent need to develop new traditional Chinese medicine compositions to optimize and overcome these limitations. Summary of the Invention

[0006] The technical problem this invention aims to solve is to overcome the shortcomings of existing traditional Chinese medicine compositions for treating diseases related to atherosclerosis, such as poor compatibility, slow onset of action, and unsatisfactory safety and compliance. This invention provides a sea buckthorn compound composition, sea buckthorn active ingredients, sea buckthorn compound preparations, their preparation methods, and applications. The sea buckthorn compound active ingredients and sea buckthorn compound preparations obtained from the sea buckthorn compound composition of this invention have excellent stability and pharmacodynamic properties, can improve vascular condition or blood lipid levels, and are suitable for treating various diseases related to arterial plaques, dyslipidemia, vascular wall thickening, or vascular endothelial inflammation.

[0007] The present invention solves the above-mentioned technical problems through the following technical solution: This invention provides a sea buckthorn compound composition, which, by mass parts, comprises the following components: 20-26 parts sea buckthorn, 17-21 parts kelp, 9-11 parts chuanxiong, 9-11 parts astragalus, 9-11 parts notoginseng, 7-9 parts earthworm, 7-9 parts scutellaria baicalensis, 7-9 parts cassia seed, 3-5 parts hawthorn, and 3-5 parts chrysanthemum.

[0008] In a preferred embodiment, the sea buckthorn compound composition comprises the following components in parts by weight: 20-26 parts sea buckthorn, 17-21 parts kelp, 9-11 parts chuanxiong, 9-11 parts astragalus, 9-11 parts notoginseng, 7-9 parts earthworm, 7-9 parts scutellaria baicalensis, 7-9 parts cassia seed, 3-5 parts hawthorn and 3-5 parts chrysanthemum.

[0009] In this invention, the sea buckthorn is preferably 21-25 parts by weight, for example 23 parts.

[0010] In this invention, the preferred mass fraction of the kelp is 18-20 parts, for example, 19 parts.

[0011] In this invention, the preferred mass fraction of Ligusticum chuanxiong is 9.5-10.5 parts, for example, 10 parts.

[0012] In this invention, the preferred mass fraction of Astragalus membranaceus is 9.5-10.5 parts, for example, 10 parts.

[0013] In this invention, the preferred mass fraction of Panax notoginseng is 9.5-10.5 parts, for example, 10 parts.

[0014] In this invention, the mass fraction of the earthworm is preferably 7.5-8.5 parts, for example 8 parts.

[0015] In this invention, the preferred mass fraction of the *Dendrobium nobile* is 7.5-8.5 parts, for example, 8 parts.

[0016] In this invention, the mass fraction of the cassia seeds is preferably 7.5-8.5 parts, for example 8 parts.

[0017] In this invention, the preferred mass fraction of hawthorn is 3.5-4.5 parts, for example, 4 parts.

[0018] In this invention, the preferred mass fraction of the chrysanthemum is 3.5-4.5 parts, for example, 4 parts.

[0019] In a preferred embodiment, the sea buckthorn compound composition comprises the following components by weight: 21-25 parts sea buckthorn, 18-20 parts kelp, 9.5-10.5 parts chuanxiong, 9.5-10.5 parts astragalus, 9.5-10.5 parts notoginseng, 7.5-8.5 parts earthworm, 7.5-8.5 parts scutellaria baicalensis, 7.5-8.5 parts cassia seed, 3.5-4.5 parts hawthorn and 3.5-4.5 parts chrysanthemum.

[0020] In a more preferred embodiment, the sea buckthorn compound composition comprises the following components in parts by weight: 21-25 parts sea buckthorn, 18-20 parts kelp, 9.5-10.5 parts chuanxiong, 9.5-10.5 parts astragalus, 9.5-10.5 parts notoginseng, 7.5-8.5 parts earthworm, 7.5-8.5 parts scutellaria baicalensis, 7.5-8.5 parts cassia seed, 3.5-4.5 parts hawthorn and 3.5-4.5 parts chrysanthemum.

[0021] In a preferred embodiment, the sea buckthorn compound composition comprises the following components by weight: 23 parts sea buckthorn, 19 parts kelp, 10 parts chuanxiong, 10 parts astragalus, 10 parts notoginseng, 8 parts earthworm, 8 parts scutellaria baicalensis, 8 parts cassia seed, 4 parts hawthorn and 4 parts chrysanthemum.

[0022] In a more preferred embodiment, the sea buckthorn compound composition comprises the following components in parts by weight: 23 parts sea buckthorn, 19 parts kelp, 10 parts chuanxiong, 10 parts astragalus, 10 parts notoginseng, 8 parts earthworm, 8 parts scutellaria baicalensis, 8 parts cassia seed, 4 parts hawthorn and 4 parts chrysanthemum.

[0023] In this invention, the sea buckthorn (Hippophae rhamnoides Linn.) Sea buckthorn refers to the dried, mature fruit of the Elaeagnaceae family plant Hippophae rhamnoides. It is harvested in autumn and winter when the fruit is ripe or frozen solid, impurities are removed, and it is dried or steamed and then dried. Sea buckthorn, in terms of its properties and meridian tropism, is sour, astringent, and warm. It enters the spleen, stomach, lung, and heart meridians. Its core functions include: strengthening the spleen and promoting digestion, invigorating blood circulation and removing blood stasis, relieving cough and expectoration, anti-oxidation, and repairing vascular endothelium.

[0024] In this invention, the kelp ( Thallus of Laminariae / Thallus of Eckloniae ) refers to kelp, a plant belonging to the Laminariaceae family ( Laminaria japonica Aresch.) Or kelp, a plant of the winged algae family ( Ecklonia kurome Okam.) The dried leaf-like foliage; harvested in summer and autumn, sun-dried; impurities removed, rinsed clean, slightly dried, cut into wide strips, and sun-dried again. Properties and Channels Entered: Salty, cold. Enters the Liver, Stomach, and Kidney channels. Core Functions: Resolves phlegm and softens hard masses, promotes diuresis and reduces swelling.

[0025] In this invention, the chuanxiong ( Chuanxiong Rhizoma) It refers to Ligusticum chuanxiong, a plant belonging to the genus Ligustrum of the family Apiaceae. Lugusticum chuanxiong Hort.) The dried rhizome; harvested in summer when the nodes on the stem are prominent and slightly purplish, removing mud and sand, sun-drying, then drying, and removing the fibrous roots; after removing impurities, separating by size, washing, moistening thoroughly, cutting into thick slices, and drying. Properties and Channels Entered: Pungent, warm. Enters the Liver, Gallbladder, and Pericardium channels. Core Functions: Invigorates blood circulation and qi, dispels wind and relieves pain.

[0026] In this invention, the Astragalus membranaceus (Astragalus membranaceus) Astragalus Root) It refers to the legume Astragalus membranaceus (Mongolian Astragalus membranaceus) Astragalus membranous var. Mongolian ) or Astragalus membranaceus ( Astragalus membranaceus Dried root; harvested in spring and autumn, fibrous roots and root heads removed, sun-dried; impurities removed, separated by size, washed, moistened thoroughly, cut into thick slices, and dried. Properties and Channels Entered: Sweet, slightly warm. Enters the Spleen and Lung channels. Core Functions: Tonifies Qi and raises Yang, strengthens Wei Qi and consolidates the exterior, promotes diuresis and reduces swelling.

[0027] In this invention, the Panax notoginseng ( notoginseng root and rhizome ) refers to Panax notoginseng, a plant of the Araliaceae family ( Panax notoginseng (BURK.) FHChen ） The dried roots and rhizomes; harvested in autumn before flowering, washed, and the main root, lateral roots, and rhizomes separated, then dried; after removing impurities, crushed or ground into a fine powder before use. The lateral roots are commonly called "tendons," and the rhizomes are commonly called "cut ends." Properties and Channels Entered: Sweet, slightly bitter, warm. Enters the Liver and Stomach channels. Core Functions: Disperses blood stasis and stops bleeding, reduces swelling and relieves pain.

[0028] In this invention, the earthworm ( Pheretima ) refers to the worm *Pheretima asiatica* (family Lumbriaceae). very good aspergillum (E. perrier), common ring-haired worm ( common pheretima Chen ) William's ringed worm ( pheretima guillemmi (Michaelsen) Or *Pteris pupa* ( Pectiniferous sea urchin Michaelsen) The dried bodies of the three species are known as "Guangdong earthworm" and "Shanghai earthworm." Guangdong earthworms are caught from spring to autumn, while Shanghai earthworms are caught in summer. The abdomen is promptly opened, the internal organs and mud removed, washed, and then sun-dried or dried at low temperature. After removing impurities, they are washed, cut into sections, and dried. Properties and Channels: Salty, cold. Enters the Liver, Spleen, and Bladder channels. Core Functions: Clears heat and calms the nerves, unblocks channels and promotes urination.

[0029] In this invention, the *Dendrobium nobile* (… Erigerontis Herb ) refers to the Asteraceae plant *Erigeron breviscapus* (also known as short-stalked f Erigeron short-headedThe dried whole herb of *Vant.) Hand.-Mazz.*; harvested in summer and autumn, impurities removed, and sun-dried. Properties and Channels Entered: pungent, slightly bitter, warm. Enters the Heart and Liver channels. Core Functions: Promotes blood circulation, unblocks channels, relieves pain, dispels wind and cold.

[0030] In this invention, the cassia seed ( Cassia Seed ) refers to the legume plant *Cassia obtusifolia* (also known as *Cassia obtusifolia*). Cassia obtuse-leafed L.) or small cassia seed ( Cassia tora Dried mature seeds of L. (L.); mature fruits are harvested in autumn, dried in the sun, threshed, and the seeds are cleaned, washed, dried, and crushed before use. Properties and Channels: Sweet, bitter, salty, slightly cold. Enters the Liver and Large Intestine channels. Core Functions: Clears liver heat and improves eyesight, moistens the intestines and promotes bowel movements, lowers lipids and blood pressure.

[0031] In this invention, the hawthorn ( Hawthorn Fruit ) refers to the Rosaceae plant Hawthorn (Haloxylon ammodendron) Hawthorn pinnate Bge. Var. older NEBr) or hawthorn ( Hawthorn pinnatifida Dried, ripe fruit of *B.* (Bge.); harvested in autumn when ripe, sliced, and dried; impurities and detached pits removed. Properties and Channels: Sour, sweet, slightly warm. Enters the Spleen, Stomach, and Liver channels. Core Functions: Promotes digestion, eliminates food stagnation, regulates Qi, and disperses blood stasis.

[0032] In this invention, the chrysanthemum ( Chrysanthemum Flower ) refers to the chrysanthemum (a plant in the Asteraceae family). Chrysanthemum marigold The dried capitulum of *Ramat.*; harvested in batches during peak bloom from September to November, dried in the shade or baked, or fumigated, steamed, and then sun-dried; the medicinal material is classified into "Haoju," "Chuju," "Gongju," "Hangju," and "Huaiju" according to its place of origin and processing method. Properties and Channels: Sweet, bitter, slightly cold. Enters the Lung and Liver channels. Core Functions: Disperses wind-heat, calms the liver and improves eyesight, clears heat and detoxifies.

[0033] In this invention, the sea buckthorn compound composition uses sea buckthorn and kelp as the two principal herbs. Sea buckthorn invigorates the spleen and promotes blood circulation, and has antioxidant properties that repair the endothelium. Kelp, being salty and cold in nature, softens hardness, resolves phlegm, and dissipates nodules. Both are used in the largest quantities to synergistically target the four major pathogenesis mechanisms of arterial plaques: phlegm, blood stasis, toxins, and deficiency. Ligusticum chuanxiong, Astragalus membranaceus, and Panax notoginseng are the assistant herbs, promoting qi circulation, tonifying qi, and resolving blood stasis, assisting the two principal herbs. Earthworm, Erigeron breviscapus, Asarum heterotropoides, and Cassia tora are the adjuvant herbs, clearing the channels, counteracting adverse effects, and lowering lipids. Hawthorn and Chrysanthemum are the guiding herbs, harmonizing and directing the formula to the meridians. The entire formula combines elimination and tonification, uses both cold and warm herbs, treats both the root cause and the symptoms, and employs a scientifically graded dosage, conforming to the principles of traditional Chinese medicine (TCM) and its principles of principal, assistant, adjuvant, and guiding herbs. Furthermore, it highly matches the mechanisms of modern pharmacology in reversing atherosclerotic plaques, making it an innovative compound TCM medicine for treating atherosclerosis and promoting plaque reversal.

[0034] In this invention, the sea buckthorn compound composition can be a sea buckthorn compound composition used to improve vascular condition or vascular level, or to treat diseases related to arterial plaque, dyslipidemia, thickening of the vascular wall or inflammation of the vascular endothelium.

[0035] The present invention also provides a method for preparing the active components of a sea buckthorn compound, which includes the following steps: using the sea buckthorn compound composition as described above as a raw material.

[0036] In this invention, the preparation method of the active components of the sea buckthorn compound preferably includes the following steps: dividing the sea buckthorn compound composition into a first composition and a second composition, wherein the first composition includes sea buckthorn, kelp, chuanxiong, astragalus, earthworm, scutellaria baicalensis, cassia seed, hawthorn and chrysanthemum, and the second composition includes earthworm, notoginseng and kelp; The preparation method of the active components of the sea buckthorn compound includes the following steps: S1. Extract the first composition with water to obtain an aqueous extract; prepare the second composition into a powder. S2. Mix the aqueous extract and the medicinal powder; The sea buckthorn compound composition consisting of the first composition and the second composition is as described above.

[0037] In this invention, the mass ratio of the water extract to the medicinal powder can be (20-25):(15-25), for example, 23.3:20.3.

[0038] In this invention, the mass ratio of kelp in the first composition to that in the second composition can be (1-1.5):(0.9-1.1), preferably (1.1-1.3):(0.95-1.05), for example 1.2:1.

[0039] In this invention, the mass ratio of earthworm in the first composition to that in the second composition can be (0.9-1.1):(1.3-1.7), preferably (0.95-1.05):(1.4-1.6), for example 1:1.5.

[0040] In a preferred embodiment, the first composition comprises the following components by weight: 20-26 parts of sea buckthorn, 9.3-11.5 parts of kelp, 9-11 parts of chuanxiong rhizome, 9-11 parts of astragalus root, 2.8-3.6 parts of earthworm, 7-9 parts of scutellaria baicalensis, 7-9 parts of cassia seed, 3-5 parts of hawthorn, and 3-5 parts of chrysanthemum.

[0041] In a preferred embodiment, the first composition comprises, by weight parts, the following components: 21-25 parts of sea buckthorn, 9.8-10.9 parts of kelp, 9.5-10.5 parts of chuanxiong rhizome, 9.5-10.5 parts of astragalus root, 3-3.4 parts of earthworm, 7.5-8.5 parts of scutellaria baicalensis, 7.5-8.5 parts of cassia seed, 3.5-4.5 parts of hawthorn, and 3.5-4.5 parts of chrysanthemum.

[0042] In a preferred embodiment, the first composition comprises the following components by weight: 23 parts sea buckthorn, 10.4 parts kelp, 10 parts chuanxiong, 10 parts astragalus, 3.2 parts earthworm, 8 parts scutellaria baicalensis, 8 parts cassia seed, 4 parts hawthorn and 4 parts chrysanthemum.

[0043] In a preferred embodiment, the first composition comprises, by weight parts, the following components: 20-26 parts of sea buckthorn, 9.3-11.5 parts of kelp, 9-11 parts of chuanxiong rhizome, 9-11 parts of astragalus root, 2.8-3.6 parts of earthworm, 7-9 parts of scutellaria baicalensis, 7-9 parts of cassia seed, 3-5 parts of hawthorn, and 3-5 parts of chrysanthemum.

[0044] In a preferred embodiment, the first composition comprises, by weight parts, the following components: 21-25 parts of sea buckthorn, 9.8-10.9 parts of kelp, 9.5-10.5 parts of chuanxiong rhizome, 9.5-10.5 parts of astragalus root, 3-3.4 parts of earthworm, 7.5-8.5 parts of scutellaria baicalensis, 7.5-8.5 parts of cassia seed, 3.5-4.5 parts of hawthorn, and 3.5-4.5 parts of chrysanthemum.

[0045] In a preferred embodiment, the first composition comprises, by weight parts, the following components: 23 parts sea buckthorn, 10.4 parts kelp, 10 parts chuanxiong, 10 parts astragalus, 3.2 parts earthworm, 8 parts scutellaria baicalensis, 8 parts cassia seed, 4 parts hawthorn and 4 parts chrysanthemum.

[0046] In this invention, the mass fraction of kelp in the second composition can be 7.7-9.5 parts, preferably 8.2-9.1 parts, for example 8.6 parts.

[0047] In this invention, the mass fraction of Panax notoginseng in the second composition can be 9-11 parts, preferably 9.5-10.5 parts, for example 10 parts.

[0048] In this invention, the mass fraction of earthworm in the second composition can be 4.2-5.4 parts, preferably 4.5-5.1 parts, for example 4.8 parts.

[0049] In a preferred embodiment, the second composition comprises, by weight parts, the following components: 7.7-9.5 parts kelp, 9-11 parts Panax notoginseng, and 4.2-5.4 parts earthworm.

[0050] In a preferred embodiment, the second composition comprises, by weight parts, the following components: 8.2-9.1 parts of kelp, 9.5-10.5 parts of Panax notoginseng, and 4.5-5.1 parts of earthworm.

[0051] In a preferred embodiment, the second composition comprises, by weight, the following components: 8.6 parts kelp, 10 parts Panax notoginseng, and 4.8 parts earthworm.

[0052] In a preferred embodiment, the second composition comprises, by weight, 7.7-9.5 parts of kelp, 9-11 parts of Panax notoginseng, and 4.2-5.4 parts of earthworm.

[0053] In a preferred embodiment, the second composition comprises, by weight, 8.2-9.1 parts of kelp, 9.5-10.5 parts of Panax notoginseng, and 4.5-5.1 parts of earthworm.

[0054] In a preferred embodiment, the second composition comprises, by weight, 8.6 parts kelp, 10 parts Panax notoginseng, and 4.8 parts earthworm.

[0055] In this invention, the extraction device can be conventional in the art, such as a multi-functional extraction tank.

[0056] In this invention, the first composition is preferably soaked in water before water extraction, for example, for 1-3 hours, or for example, for 2 hours.

[0057] In this invention, the mass ratio of the first composition to the water can be 1:(6-12), preferably 1:(7-9), for example 1:10 or 1:8.

[0058] In this invention, the water extraction temperature can be 90-110℃, for example, 100℃.

[0059] In this invention, the water extraction time can be 1-5 hours, for example, 2 or 4 hours.

[0060] In this invention, the water extraction can be performed twice.

[0061] In this invention, the steam pressure for water extraction can be 0.08-0.10 MPa, for example 0.09 MPa.

[0062] In a preferred embodiment, the water extraction includes the following steps: The first composition was subjected to a first water extraction to obtain an intermediate water extract; The intermediate water extract is subjected to a second water extraction to obtain the water extract.

[0063] In the first water extraction, the mass ratio of the first composition to the water is 1:(6-12), preferably 1:(7-9), for example 1:10.

[0064] The temperature of the first water extraction is 90-110℃, for example, 100℃.

[0065] The steam pressure for the first water extraction is 0.08-0.10 MPa, for example, 0.09 MPa.

[0066] The first water extraction takes 1-3 hours, for example, 2 hours.

[0067] In the second water extraction, the mass ratio of the intermediate water extract to the water is 1:(6-12), preferably 1:(7-9), for example 1:8.

[0068] The temperature of the second water extraction is 90-110℃, for example, 100℃.

[0069] The second water extraction takes 1-3 hours, for example, 2 hours.

[0070] The steam pressure for the second water extraction is 0.08-0.10 MPa, for example, 0.09 MPa.

[0071] In this invention, after water extraction, the extract is preferably obtained through solid-liquid separation. The solid-liquid separation is preferably filtration.

[0072] Preferably, the extract is concentrated to obtain a concentrated solution. The pressure during concentration is preferably 0.05-0.10 MPa, for example, 0.08 MPa. The relative density of the concentrated solution is preferably 1.0-1.4 g / cm³. 3 For example, 1.2 or 1.25 g / cm³ 3 The concentrate preferably further undergoes drying and pulverizing steps. The drying operation can be conventional in the art, for example, carried out in a vacuum dryer. The drying temperature is preferably 60-100°C, for example 70°C. The drying time is preferably 4-8 hours, for example 6 hours.

[0073] In this invention, the mesh size of the water extract is preferably 100-140 mesh, for example 120 mesh.

[0074] In this invention, the mesh size of the powder can be 80-120 mesh, for example, 100 mesh.

[0075] In this invention, the method for preparing the powder preferably includes the following steps: pulverizing, sterilizing, drying, and pulverizing the second composition in sequence.

[0076] The sterilization process can be performed according to conventional methods in the art, such as in an autoclave. The sterilization temperature is preferably 120-130°C, for example, 121°C. The sterilization time is preferably 30-40 minutes, for example, 35 minutes. The sterilization pressure is preferably 60-80 kPa, for example, 60-75 kPa.

[0077] The drying process is carried out, for example, in an oven. The drying temperature is preferably 70-90°C, for example, 80°C. The drying time is preferably 1-2 hours, for example, 1.5 hours.

[0078] The present invention also provides a compound active ingredient of sea buckthorn, which is prepared by the preparation method of the compound active ingredient of sea buckthorn as described above.

[0079] The present invention also provides a compound active ingredient of sea buckthorn, which includes an aqueous extract and a medicinal powder; the aqueous extract is an aqueous extract of a first composition; the first composition includes sea buckthorn, kelp, chuanxiong, astragalus, earthworm, scutellaria baicalensis, cassia seed, hawthorn and chrysanthemum; the medicinal powder is a medicinal powder of a second composition, the second composition including earthworm, notoginseng and kelp; The sea buckthorn compound composition consisting of the first composition and the second composition is the sea buckthorn compound composition as described above.

[0080] In this invention, the mass ratio of the water extract to the medicinal powder can be (20-25):(15-25), for example, 23.3:20.3.

[0081] In this invention, the mass ratio of kelp in the first composition to that in the second composition can be (1-1.5):(0.9-1.1), preferably (1.1-1.3):(0.95-1.05), for example 1.2:1.

[0082] In this invention, the mass ratio of earthworm in the first composition to that in the second composition can be (0.9-1.1):(1.3-1.7), preferably (0.95-1.05):(1.4-1.6), for example 1:1.5.

[0083] In a preferred embodiment, the first composition comprises the following components by weight: 20-26 parts of sea buckthorn, 9.3-11.5 parts of kelp, 9-11 parts of chuanxiong rhizome, 9-11 parts of astragalus root, 2.8-3.6 parts of earthworm, 7-9 parts of scutellaria baicalensis, 7-9 parts of cassia seed, 3-5 parts of hawthorn, and 3-5 parts of chrysanthemum.

[0084] In a preferred embodiment, the first composition comprises, by weight parts, the following components: 21-25 parts of sea buckthorn, 9.8-10.9 parts of kelp, 9.5-10.5 parts of chuanxiong rhizome, 9.5-10.5 parts of astragalus root, 3-3.4 parts of earthworm, 7.5-8.5 parts of scutellaria baicalensis, 7.5-8.5 parts of cassia seed, 3.5-4.5 parts of hawthorn, and 3.5-4.5 parts of chrysanthemum.

[0085] In a preferred embodiment, the first composition comprises the following components by weight: 23 parts sea buckthorn, 10.4 parts kelp, 10 parts chuanxiong, 10 parts astragalus, 3.2 parts earthworm, 8 parts scutellaria baicalensis, 8 parts cassia seed, 4 parts hawthorn and 4 parts chrysanthemum.

[0086] In a preferred embodiment, the first composition comprises, by weight parts, the following components: 20-26 parts of sea buckthorn, 9.3-11.5 parts of kelp, 9-11 parts of chuanxiong rhizome, 9-11 parts of astragalus root, 2.8-3.6 parts of earthworm, 7-9 parts of scutellaria baicalensis, 7-9 parts of cassia seed, 3-5 parts of hawthorn, and 3-5 parts of chrysanthemum.

[0087] In a preferred embodiment, the first composition comprises, by weight parts, the following components: 21-25 parts of sea buckthorn, 9.8-10.9 parts of kelp, 9.5-10.5 parts of chuanxiong rhizome, 9.5-10.5 parts of astragalus root, 3-3.4 parts of earthworm, 7.5-8.5 parts of scutellaria baicalensis, 7.5-8.5 parts of cassia seed, 3.5-4.5 parts of hawthorn, and 3.5-4.5 parts of chrysanthemum.

[0088] In a preferred embodiment, the first composition comprises, by weight parts, the following components: 23 parts sea buckthorn, 10.4 parts kelp, 10 parts chuanxiong, 10 parts astragalus, 3.2 parts earthworm, 8 parts scutellaria baicalensis, 8 parts cassia seed, 4 parts hawthorn and 4 parts chrysanthemum.

[0089] In this invention, the mass fraction of kelp in the second composition can be 7.7-9.5 parts, preferably 8.2-9.1 parts, for example 8.6 parts.

[0090] In this invention, the mass fraction of Panax notoginseng in the second composition can be 9-11 parts, preferably 9.5-10.5 parts, for example 10 parts.

[0091] In this invention, the mass fraction of earthworm in the second composition can be 4.2-5.4 parts, preferably 4.5-5.1 parts, for example 4.8 parts.

[0092] In a preferred embodiment, the second composition comprises, by weight parts, the following components: 7.7-9.5 parts kelp, 9-11 parts Panax notoginseng, and 4.2-5.4 parts earthworm.

[0093] In a preferred embodiment, the second composition comprises, by weight parts, the following components: 8.2-9.1 parts of kelp, 9.5-10.5 parts of Panax notoginseng, and 4.5-5.1 parts of earthworm.

[0094] In a preferred embodiment, the second composition comprises, by weight, the following components: 8.6 parts kelp, 10 parts Panax notoginseng, and 4.8 parts earthworm.

[0095] In a preferred embodiment, the second composition comprises, by weight, 7.7-9.5 parts of kelp, 9-11 parts of Panax notoginseng, and 4.2-5.4 parts of earthworm.

[0096] In a preferred embodiment, the second composition comprises, by weight, 8.2-9.1 parts of kelp, 9.5-10.5 parts of Panax notoginseng, and 4.5-5.1 parts of earthworm.

[0097] In a preferred embodiment, the second composition comprises, by weight, 8.6 parts kelp, 10 parts Panax notoginseng, and 4.8 parts earthworm.

[0098] In this invention, the water extract can be obtained using the preparation method described above.

[0099] In this invention, the active components of the sea buckthorn compound can be sea buckthorn compound active components used to improve vascular condition or vascular level, or to treat diseases related to arterial plaque, dyslipidemia, thickening of the vascular wall or inflammation of the vascular endothelium.

[0100] The present invention also provides a sea buckthorn compound preparation comprising the sea buckthorn compound active ingredients as described above and pharmaceutically acceptable excipients.

[0101] In this invention, the pharmaceutically acceptable excipients preferably include one or more of unmodified starch, pregelatinized starch, microcrystalline cellulose, sucrose, sodium carboxymethyl starch, magnesium stearate, and silicon dioxide, such as unmodified starch, pregelatinized starch, microcrystalline cellulose, and sucrose; or sodium carboxymethyl starch, magnesium stearate, and silicon dioxide.

[0102] In this invention, the preferred ratio of the mass of the pharmaceutically acceptable excipient to the total mass of the sea buckthorn compound composition is (20-30):97.9, for example, 28.7:97.9, 26.5:97.9 or 28.6:97.9.

[0103] In this invention, the preferred mass ratio of the pharmaceutically acceptable excipient to the powder is (20-30):(15-25), more preferably (25-29):(18-21), for example 28.7:20.3, 26.5:20.3 or 28.6:20.3.

[0104] In this invention, the preferred mass ratio of the pharmaceutically acceptable excipient to the water extract is (20-30):(15-25), more preferably (25-29):(21-24), for example 28.7:23.3, 26.5:23.3 or 28.6:23.3.

[0105] In this invention, the dosage form of the sea buckthorn compound preparation is preferably capsule, tablet, powder, oral liquid, pill, tincture, syrup, suppository, gel, spray or granule, such as granules or tablets.

[0106] In a preferred embodiment, the sea buckthorn compound preparation is a sea buckthorn compound granule, which includes the sea buckthorn compound active ingredients as described above and pharmaceutically acceptable excipients.

[0107] The preferred ratio of the mass of the pharmaceutically acceptable excipient to the total mass of the sea buckthorn compound composition is (20-30):97.9, for example, 26.5:97.9.

[0108] The preferred mass ratio of the pharmaceutically acceptable excipient to the powder is (20-30):(15-25), more preferably (25-29):(18-21), for example 26.5:20.3.

[0109] The preferred mass ratio of the pharmaceutically acceptable excipient to the water extract is (20-30):(20-30), more preferably (25-29):(21-25), for example 26.5:23.3.

[0110] The pharmaceutically acceptable excipients may include unmodified starch, pregelatinized starch, microcrystalline cellulose, and sucrose.

[0111] The preferred mass ratio of unmodified starch, pregelatinized starch, microcrystalline cellulose and sucrose is 10:(5-10):(5-10):(1-5), for example 10:6.6:6.6:3.3.

[0112] The unmodified starch accounts for 5%-15% of the mass percentage of the sea buckthorn compound composition, for example, 10.2%.

[0113] The pregelatinized starch accounts for 5%-12% of the mass percentage of the sea buckthorn compound composition, for example, 6.7%.

[0114] The microcrystalline cellulose accounts for 5%-12% of the mass percentage of the sea buckthorn compound composition, for example, 6.7%.

[0115] The sucrose constitutes 1%-5% of the mass of the sea buckthorn compound composition, for example, 3.4%.

[0116] The mass of the unmodified starch is preferably 40%-50% of the mass of the water extract, for example, 42.9%.

[0117] The mass of the pregelatinized starch is preferably 20%-30% of the mass of the water extract, for example, 28.3%.

[0118] The mass of the microcrystalline cellulose is preferably 20%-30% of the mass of the water extract, for example, 28.3%.

[0119] The mass of the sucrose is preferably 10%-20% of the mass of the water extract, for example, 14.2%.

[0120] The preferred mass ratio of the unmodified starch to the medicinal powder is (8-12):(15-25), for example, 10:20.3.

[0121] The preferred mass ratio of the pregelatinized starch to the medicinal powder is (3-8):(15-25), for example, 6.6:20.3.

[0122] The preferred mass ratio of the microcrystalline cellulose to the powdered medicine is (3-8):(15-25), for example, 6.6:20.3.

[0123] The preferred mass ratio of sucrose to the powdered medicine is (1-5):(15-25), for example, 3.3:20.3.

[0124] The preferred particle size of the sucrose is 80-120 mesh, for example, 100 mesh.

[0125] The sea buckthorn compound granules are preferably 10-20 mesh, for example, 16 mesh.

[0126] In a preferred embodiment, the sea buckthorn compound preparation is a sea buckthorn compound tablet, which includes the sea buckthorn compound active ingredient as described above, a first pharmaceutically acceptable excipient, and a second pharmaceutically acceptable excipient; the first pharmaceutically acceptable excipient includes unmodified starch, pregelatinized starch, microcrystalline cellulose, and sucrose; the second pharmaceutically acceptable excipient includes sodium carboxymethyl starch, magnesium stearate, and silicon dioxide.

[0127] The preferred mass ratio of the first pharmaceutically acceptable excipient to the second pharmaceutically acceptable excipient is (20-30):(2-3), for example, 26.5:2.2 or 26.5:2.1.

[0128] The preferred ratio of the mass of the first pharmaceutically acceptable excipient to the total mass of the sea buckthorn compound composition is (20-30):97.9, for example, 26.5:97.9.

[0129] The preferred mass ratio of the first pharmaceutically acceptable excipient to the powder is (20-30):(15-25), more preferably (25-29):(18-21), for example 26.5:20.3.

[0130] The preferred mass ratio of the first pharmaceutically acceptable excipient to the water extract is (20-30):(20-30), more preferably (25-29):(21-25), for example 26.5:23.3.

[0131] In the first pharmaceutically acceptable excipient, the mass ratio of the unmodified starch, the pregelatinized starch, the microcrystalline cellulose and the sucrose is preferably 10:(5-10):(5-10):(1-5), for example 10:6.6:6.6:3.3.

[0132] The unmodified starch accounts for 5%-15% of the mass percentage of the sea buckthorn compound composition, for example, 10.2%.

[0133] The pregelatinized starch accounts for 5%-12% of the mass percentage of the sea buckthorn compound composition, for example, 6.7%.

[0134] The microcrystalline cellulose accounts for 5%-12% of the mass percentage of the sea buckthorn compound composition, for example, 6.7%.

[0135] The sucrose constitutes 1%-5% of the mass of the sea buckthorn compound composition, for example, 3.4%.

[0136] The mass of the unmodified starch is preferably 40%-50% of the mass of the water extract, for example, 42.9%.

[0137] The mass of the pregelatinized starch is preferably 20%-30% of the mass of the water extract, for example, 28.3%.

[0138] The mass of the microcrystalline cellulose is preferably 20%-30% of the mass of the water extract, for example, 28.3%.

[0139] The mass of the sucrose is preferably 10%-20% of the mass of the water extract, for example, 14.2%.

[0140] The preferred mass ratio of the unmodified starch to the medicinal powder is (8-12):(15-25), for example, 10:20.3.

[0141] The preferred mass ratio of the pregelatinized starch to the medicinal powder is (3-8):(15-25), for example, 6.6:20.3.

[0142] The preferred mass ratio of the microcrystalline cellulose to the powdered medicine is (3-8):(15-25), for example, 6.6:20.3.

[0143] The preferred mass ratio of sucrose to the powdered medicine is (1-5):(15-25), for example, 3.3:20.3.

[0144] The preferred particle size of the sucrose is 80-120 mesh, for example, 100 mesh.

[0145] The preferred ratio of the mass of the second pharmaceutically acceptable excipient to the total mass of the sea buckthorn compound composition is (1-5):97.9, for example, 2.2:97.9 or 2.1:97.9.

[0146] The preferred mass ratio of the second pharmaceutically acceptable excipient to the powder is (1-5):(15-25), more preferably (2-3):(18-21), for example 2.2:20.3 or 2.1:20.3.

[0147] The preferred mass ratio of the second pharmaceutically acceptable excipient to the water extract is (1-5):(20-30), more preferably (2-3):(21-25), for example 2.2:23.3 or 2.1:23.3.

[0148] In the second pharmaceutically acceptable excipient, the preferred mass ratio of sodium carboxymethyl starch, magnesium stearate, and silicon dioxide is (1-3):1:(0.05-0.15), for example, 2:1:0.1 or 1.91:0.1.

[0149] The sodium carboxymethyl starch accounts for 1%-3% of the mass percentage of the sea buckthorn compound composition, for example, 1.43% or 1.33%.

[0150] The magnesium stearate may account for 0.1%-1.0% of the mass percentage of the sea buckthorn compound composition, for example, 0.72%.

[0151] The silica accounts for 0.05%-0.15% of the mass of the sea buckthorn compound composition, for example, 0.10%.

[0152] The preferred mass ratio of sodium carboxymethyl starch to the powder is (1-5):(15-25), for example, 1.4:20.3 or 1.3:20.3.

[0153] The preferred mass ratio of magnesium stearate to the powdered medicine is (0.1-1.0):(15-25), for example, 0.7:20.3.

[0154] The preferred mass ratio of the silica to the powder is (0.05-0.15):(15-25), for example, 0.1:20.3.

[0155] The preferred mass of sodium carboxymethyl starch is 1%-3% of the sum of the mass of the active component of the sea buckthorn compound and the first pharmaceutically acceptable excipient, for example, 2% or 1.85%.

[0156] The preferred mass of the magnesium stearate is 0.5%-1.5% of the sum of the mass of the active component of the sea buckthorn compound and the first pharmaceutically acceptable excipient, for example, 1%.

[0157] The mass of the silica is preferably 0.1%-0.3% of the sum of the mass of the active component of the sea buckthorn compound and the first pharmaceutically acceptable excipient, for example, 0.14%.

[0158] The sea buckthorn compound tablets can be in the specification of 0.52g / tablet.

[0159] The present invention also provides a method for preparing the sea buckthorn compound preparation as described above, which includes the following steps: mixing the active components of the sea buckthorn compound preparation as described above with the pharmaceutically acceptable excipients.

[0160] In a preferred embodiment, the sea buckthorn compound preparation is a sea buckthorn compound granule, and the preparation method of the sea buckthorn compound granule includes the following steps: The active components of the sea buckthorn compound are mixed with pharmaceutically acceptable excipients, granulated by wet granulation, and dried to obtain the sea buckthorn compound granules.

[0161] In the wet granulation process, the solvent is preferably an aqueous ethanol solution. The mass concentration of ethanol in the aqueous ethanol solution is preferably 30%-70%, for example, 40%, 50% or 60%. The amount of the aqueous ethanol solution is preferably 1.0-1.5 times the mass of the water extract, for example, 1.1 times.

[0162] The equipment used in the wet granulation process is preferably a 16-mesh stainless steel sieve.

[0163] The drying operation can be conventional in the art, such as drying at 80°C and 0.15MPa for 5 hours.

[0164] In a preferred embodiment, the sea buckthorn compound preparation is a sea buckthorn compound tablet, which is prepared by compressing the sea buckthorn compound granules.

[0165] In a preferred embodiment, the sea buckthorn compound preparation is a sea buckthorn compound tablet, and the preparation method of the sea buckthorn compound tablet includes the following steps: S1. The active components of the sea buckthorn compound and the first pharmaceutically acceptable excipient are mixed, granulated by wet granulation process, and dried to obtain sea buckthorn compound granules. S2. Mix the seabuckthorn compound granules with a second pharmaceutically acceptable excipient and compress into tablets.

[0166] The tableting equipment can be conventional in the art, such as a rotary tablet press.

[0167] The diameter of the punch used for tableting can be 12.0 mm.

[0168] The pressure during tablet compression can be 8-12 kN, for example, 10 kN.

[0169] The rotation speed during tablet compression can be 20-30 rpm, for example, 22 rpm.

[0170] The present invention also provides the use of the aforementioned sea buckthorn compound composition, the aforementioned sea buckthorn compound active ingredient, or the aforementioned sea buckthorn compound preparation in the preparation of a drug for improving vascular condition or blood lipid levels or a drug for treating diseases, wherein the diseases are related to arterial plaques, dyslipidemia, thickening of the vascular wall, or inflammation of the vascular endothelium.

[0171] In this invention, the application can be in the preparation of drugs that reverse vulnerable atherosclerotic plaques, reverse calcified atherosclerotic plaques, reverse mixed atherosclerotic plaques, improve dyslipidemia, improve thickened blood vessel walls, and improve or eliminate inflammation of the vascular endothelium.

[0172] In this invention, the application can be in the preparation of medicaments for treating diseases related to atherosclerosis, stenosis or detachment of arterial plaques.

[0173] In this invention, the application can be in the preparation of medicaments for treating diseases related to coronary atherosclerosis, carotid plaque stenosis or detachment, or systemic atherosclerosis.

[0174] In this invention, the application can be in the preparation of drugs for treating coronary heart disease, angina pectoris, myocardial infarction, cerebral infarction or ischemic stroke.

[0175] In this invention, the vascular state refers to the distribution and density of blood vessels in tissues or organs, plaques in blood vessels, the thickness of the blood vessel wall, or whether inflammation occurs in the inner wall of blood vessels.

[0176] In this invention, blood lipids refer to the total amount of lipids and lipid-like substances in the blood, which is an important indicator for measuring cardiovascular health.

[0177] In this invention, the arterial plaque refers to a lipid deposition lesion formed within the arterial wall, which is composed of lipids, fibrous tissue, calcification, and other substances.

[0178] In this invention, the term "dyslipidemia" refers to a complex disorder of lipoprotein metabolism, including excessive production or abnormal metabolism of lipoproteins. Dyslipidemia may manifest as elevated total cholesterol, elevated levels of low-density lipoprotein (LDL) cholesterol and triglycerides, and decreased levels of high-density lipoprotein (HDL) cholesterol in the blood.

[0179] In this invention, the thickening of the blood vessel wall refers to the increased thickness of each layer of the blood vessel wall (intima, media, and adventitia), which is an early manifestation of various vascular diseases.

[0180] In this invention, the vascular wall inflammation refers to inflammatory diseases of the vascular wall, which is a general term for a group of diseases characterized by vascular wall inflammation and necrosis.

[0181] In this invention, the atherosclerotic vulnerable plaque refers to an atherosclerotic plaque that is prone to rupture, leading to cardiovascular events such as acute myocardial infarction and stroke.

[0182] In this invention, the atherosclerotic calcified plaques refer to sclerotic plaques formed on the arterial wall due to calcium salt deposition, which are a late-stage manifestation of atherosclerosis.

[0183] In this invention, the atherosclerotic mixed plaque refers to a plaque caused by the accumulation of lipids, macrophages, T lymphocytes, smooth muscle cells, extracellular matrix, calcium, and necrotic debris, resulting in thickening of the arterial wall; the vascular wall simultaneously contains a lipid core, fibrous tissue, and calcified components.

[0184] In this invention, the term "atherosclerosis" refers to a vascular disease characterized by irregularly distributed lipid deposits in the intima of large and medium-sized arteries, sometimes leading to narrowing of the arterial lumen and eventually progressing to fibrosis and calcification. The lesions are typically focal and progress slowly and intermittently. Restriction of blood flow is the cause of most clinical presentations, varying with the distribution and severity of the lesions.

[0185] In this invention, arterial plaque stenosis refers to the narrowing of the arterial lumen due to the enlargement of plaque.

[0186] In this invention, the term "arterial plaque detachment" refers to the detachment of plaques or plaque fragments from the artery and their entry into the cerebral artery via the bloodstream.

[0187] In this invention, coronary atherosclerosis refers to the pathological process in which lipid deposition on the inner wall of the coronary arteries forms plaques, leading to narrowing or blockage of the blood vessels.

[0188] In this invention, carotid plaque stenosis refers to the narrowing of the carotid artery lumen due to the enlargement of plaques.

[0189] In this invention, carotid plaque detachment refers to the detachment of plaque or plaque fragments from the carotid artery and their entry into the cerebral artery via the bloodstream.

[0190] In this invention, systemic atherosclerosis refers to atherosclerotic lesions affecting large and medium-sized arteries in multiple parts of the body.

[0191] In this invention, coronary heart disease, also known as coronary artery disease, is the narrowing of the arteries that supply blood to the heart.

[0192] In this invention, angina pectoris refers to paroxysmal chest pain caused by insufficient blood supply to the coronary arteries, leading to myocardial ischemia and hypoxia.

[0193] In this invention, myocardial infarction refers to myocardial ischemia and necrosis caused by complete blockage of the coronary artery.

[0194] In this invention, cerebral infarction refers to a disease caused by impaired blood supply to the brain, leading to ischemic necrosis of brain tissue.

[0195] In this invention, the term "stroke" refers to a situation where the blood supply to a part of the brain is cut off.

[0196] Based on common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0197] The reagents and raw materials used in this invention are all commercially available.

[0198] The positive and progressive effects of this invention are as follows: (1) In the sea buckthorn compound composition of the present invention, sea buckthorn and kelp are used as the two principal drugs, chuanxiong, astragalus and notoginseng are used as the assistant drugs, earthworm, scutellaria baicalensis and cassia seed are used as the adjuvant drugs, and hawthorn and chrysanthemum are used as the guide drugs. The sea buckthorn compound composition conforms to the traditional Chinese medicine principal, assistant and adjuvant drug standard, and each component is used to eliminate and replenish, and to treat both cold and warm, and to treat both the root cause and the symptoms.

[0199] (2) The active components or preparations of sea buckthorn compound prepared by using the sea buckthorn compound composition of the present invention have excellent stability and pharmacodynamic properties, and can improve vascular condition or blood lipid level (for example, it can significantly increase carotid blood flow velocity and improve the degree of carotid lumen obstruction; its comprehensive performance in improving arterial plaque diseases is far superior to statin drugs), and is suitable for treating various diseases related to arterial plaques, dyslipidemia, thickening of blood vessel walls or inflammation of blood vessel walls.

[0200] (3) The active components of the sea buckthorn compound of the present invention preferably adopt a unique method of adding kelp and earthworm in two steps. The active components and preparations of sea buckthorn compound prepared by this method have better stability and pharmacodynamic properties. Detailed Implementation

[0201] The present invention will be further illustrated by way of embodiments below, but the present invention is not limited to the scope of the embodiments described herein.

[0202] The list of abbreviations used in the following effect examples is shown in the table below: Abbreviation list

[0203] Example 1

[0204] The sea buckthorn compound composition consists of the following components: Sea buckthorn 23 parts, kelp 19 parts, chuanxiong 10 parts, astragalus 10 parts, notoginseng 10 parts, earthworm 8 parts, scutellaria baicalensis 8 parts, cassia seed 8 parts, hawthorn 4 parts and chrysanthemum 4 parts.

[0205] It is divided into a first composition and a second composition, wherein, The first composition consists of 23 parts sea buckthorn, 10.4 parts kelp, 10 parts chuanxiong, 10 parts astragalus, 3.2 parts earthworm, 8 parts scutellaria baicalensis, 8 parts cassia seed, 4 parts hawthorn and 4 parts chrysanthemum; the total mass of the first composition is 77.6 kg. The second composition consists of 4.8 parts earthworm, 10 parts Panax notoginseng, and 8.6 parts kelp; the total mass of the first composition is 20.3 kg.

[0206] The preparation method of sea buckthorn compound tablets (MH-001) is as follows: S1. Preparation of active components of sea buckthorn compound: (1) Weigh the first composition according to the prescription and add it to the multi-functional extraction tank. Add 10 times the amount of water, soak for two hours, start the boiling time, and extract for the first time for two hours at 100°C and steam pressure of 0.09MPa. (2) Drain the liquid and filter it. Then add 8 times the amount of water, boil and start timing. Extract for the second time at 100℃ and steam pressure of 0.09MPa for two hours. Filter and combine the filtrates. (3) The filtrate was concentrated using a double-effect concentrator. At a steam pressure of 0.08 MPa, the double-effect concentrator was turned on to achieve a vacuum of -0.04 MPa and a temperature of 84°C in the first effect. The first effect feed valve was opened, and the filtrate was added to the first effect. When the filtrate rose to half the height of the lower sight glass of the first effect evaporation chamber, the first effect feed valve was closed, and the heater steam valve was turned on to raise the temperature. At a vacuum of -0.07 MPa and a temperature of 72°C in the second effect, the second effect feed valve was opened to feed the filtrate. When the filtrate rose to half the height of the lower sight glass of the second effect evaporation chamber, the feed valve was closed. A relative density of 1.25 g / cm³ was obtained. 3 The wet extract (measured at 60℃) (with a yield of 56.17%, yield = total mass of wet extract / total mass of first composition × 100%) was released for later use. (4) Place the water extract in a vacuum dryer and dry it at 70°C for 6 hours; (5) Powder the water extract into a dry powder by passing it through a 120-mesh sieve using a pulverizer, and set aside for later use; (6) Mix and pulverize the second composition through a 100-mesh sieve, then put it into a hot press sterilizer and sterilize it at 121°C and 75 kPa for 35 minutes. Take it out and dry it in an oven at 80°C for 1.5 hours. Take it out and pulverize it through a 100-mesh sieve to obtain the powder for later use. The mass ratio of water extract to powder in the active components of the sea buckthorn compound is 23.3:20.3.

[0207] S2. Preparation of Seabuckthorn Compound Tablets

[0208] (1) Prepare auxiliary materials

[0209] First pharmaceutically acceptable excipient: unmodified starch, pregelatinized starch, microcrystalline cellulose and sucrose powder in a mass ratio of 10:6.6:6.6:3.3; The second pharmaceutically acceptable excipient is sodium carboxymethyl starch, magnesium stearate, and silicon dioxide in a mass ratio of 2:1:0.1. The mass ratio of the first pharmaceutically acceptable excipient to the second pharmaceutically acceptable excipient is 26.5:2.2. The ratio of the mass of the first pharmaceutically acceptable excipient to the total mass of the sea buckthorn compound composition is 26.5:97.9; the ratio of the mass of the second pharmaceutically acceptable excipient to the total mass of the sea buckthorn compound composition is 2.2:97.9. The first pharmaceutically acceptable excipient to powder mass ratio is 26.5:20.3; the second pharmaceutically acceptable excipient to powder mass ratio is 2.2:20.3.

[0210] In this process, sucrose is pulverized using a pulverizer and passed through a 100-mesh sieve to obtain sucrose powder.

[0211] (2) Mix 26.5 kg of pharmaceutically acceptable excipients (10 kg of unmodified starch, 6.6 kg of pregelatinized starch, 6.6 kg of microcrystalline cellulose, and 3.3 kg of sucrose powder), 20.3 kg of medicinal powder, and 23.3 kg of water extract powder for 20 minutes until homogeneous; the unmodified starch can account for 10.2% of the mass of the sea buckthorn compound composition; the pregelatinized starch can account for 6.7% of the mass of the sea buckthorn compound composition; the microcrystalline cellulose can account for 6.7% of the mass of the sea buckthorn compound composition; and the sucrose can account for 3.4% of the mass of the sea buckthorn compound composition. (3) Add 25.7 kg of 50% ethanol aqueous solution and mix for 15 minutes until homogeneous; (4) Use a 16-mesh stainless steel sieve to make uniform wet granules, dry them in an oven at 80℃ and 0.15MPa for 5 hours, and then pass them through a 16-mesh sieve to obtain sea buckthorn compound granules.

[0212] (5) Mix 67.7 kg of sea buckthorn compound granules and 2.2 kg of a second pharmaceutically acceptable excipient for 30 minutes until homogeneous; wherein, the second pharmaceutically acceptable excipient accounts for 3.2% of the mass of the sea buckthorn compound granules (2% sodium carboxymethyl starch, 1% magnesium stearate and 0.1% silicon dioxide, the percentage refers to the mass percentage of sodium carboxymethyl starch, magnesium stearate or silicon dioxide in the sea buckthorn compound granules); sodium carboxymethyl starch accounts for 1.43% of the mass of the sea buckthorn compound composition; magnesium stearate accounts for 0.72% of the mass of the sea buckthorn compound composition; silicon dioxide accounts for 0.10% of the mass of the sea buckthorn compound composition; the mass of sodium carboxymethyl starch is 2.00% of the sum of the mass of the active component of the sea buckthorn compound and the first pharmaceutically acceptable excipient; the mass of magnesium stearate is 1.00% of the sum of the mass of the active component of the sea buckthorn compound and the first pharmaceutically acceptable excipient; the mass of silicon dioxide is 0.14% of the sum of the mass of the active component of the sea buckthorn compound and the first pharmaceutically acceptable excipient. (6) A rotary tablet press is used to compress tablets. The diameter of the punch of the tablet press is 12.0 mm. The tablets are compressed to 0.52 g / tablet under a pressure of 10 KN and a rotation speed of 22 rpm.

[0213] Example 2

[0214] The composition of the sea buckthorn compound is the same as in Example 1; The preparation method of sea buckthorn compound tablets (MH-002) is as follows: S1. Preparation of the active components of the sea buckthorn compound is the same as in Example 1; S2. Preparation of Seabuckthorn Compound Tablets (1) Prepare auxiliary materials First pharmaceutically acceptable excipient: unmodified starch, pregelatinized starch, microcrystalline cellulose and sucrose powder in a mass ratio of 10:6.6:6.6:3.3; The second pharmaceutically acceptable excipient is sodium carboxymethyl starch, magnesium stearate, and silicon dioxide in a mass ratio of 1.9:1:0.1. The mass ratio of the first pharmaceutically acceptable excipient to the second pharmaceutically acceptable excipient is 26.5:2.1; The ratio of the mass of the first pharmaceutically acceptable excipient to the total mass of the sea buckthorn compound composition is 26.5:97.9; the ratio of the mass of the second pharmaceutically acceptable excipient to the total mass of the sea buckthorn compound composition is 2.1:97.9. The first pharmaceutically acceptable excipient to powder mass ratio is 26.5:20.3; the second pharmaceutically acceptable excipient to powder mass ratio is 2.1:20.3.

[0215] In this process, sucrose is pulverized using a pulverizer and passed through a 100-mesh sieve to obtain sucrose powder.

[0216] (2) Same as Example 1; (3) Same as Example 1; (4) Same as Example 1; (5) Mix 66.8 kg of sea buckthorn compound granules and 2.1 kg of a second pharmaceutically acceptable excipient for 30 minutes until homogeneous; wherein, the second pharmaceutically acceptable excipient accounts for 3.1% of the mass of the sea buckthorn compound granules (1.9% sodium carboxymethyl starch, 1% magnesium stearate and 0.1% silicon dioxide, the percentage refers to the mass percentage of sodium carboxymethyl starch, magnesium stearate or silicon dioxide in the sea buckthorn compound granules); sodium carboxymethyl starch accounts for 1.33% of the mass of the sea buckthorn compound composition; magnesium stearate accounts for 0.72% of the mass of the sea buckthorn compound composition; silicon dioxide accounts for 0.10% of the mass of the sea buckthorn compound composition; the mass of sodium carboxymethyl starch is 1.85% of the sum of the mass of the active component of the sea buckthorn compound and the first pharmaceutically acceptable excipient; the mass of magnesium stearate is 1.00% of the sum of the mass of the active component of the sea buckthorn compound and the first pharmaceutically acceptable excipient; the mass of silicon dioxide is 0.14% of the sum of the mass of the active component of the sea buckthorn compound and the first pharmaceutically acceptable excipient. (6) Same as Example 1.

[0217] Example 1: Finished Product Inspection

[0218] According to the General Rules of Part IV of the 2025 edition of the Chinese Pharmacopoeia, the sea buckthorn compound tablets (MH-001) prepared in Example 1 were subjected to finished product testing (including appearance, disintegration time, friability, weight variation and microbial limits). The properties are assessed visually. Specifically, take an appropriate amount of tablets (usually 10 tablets), place them under natural light or a standard lamp, and observe them visually. Appearance: intact and smooth, uniform in color, without cracks, missing corners, pitting, adhesion, foreign matter, spots, or discoloration. Record: color, shape, etc.

[0219] The disintegration time was tested using a lifting disintegration apparatus. The test method was as follows: six tablets of the sea buckthorn compound tablets (MH-001) prepared in Example 1 were taken and placed in the glass tube of the basket, immersed in the medium, and the lifting mechanism was activated (30-32 times / min, stroke 55mm±2mm). The time was recorded, and the time for each tablet to completely disintegrate (pass through the sieve without a hard core) was observed and recorded. The average value was taken.

[0220] The friability was tested using a friability tester. The test method was as follows: 10 tablets of the sea buckthorn compound tablets (MH-001) prepared in Example 1 were taken, and the floating powder was blown off with a hair dryer. The tablets were then weighed accurately (W1). The tablets were placed in a cylinder (transparent plastic cylinder, inner diameter approximately 286 mm, rotation speed 25 rpm ± 1 rpm) and rotated 100 times. The tablets were then removed, the powder was removed in the same way, and the tablets were weighed accurately (W2). The weight loss (%) = (W1 - W2)W1 × 100%.

[0221] The weight difference was tested using an analytical balance. The test method was as follows: 20 tablets of the sea buckthorn compound tablets (MH-001) prepared in Example 1 were taken, the total weight was accurately measured, and the average tablet weight was calculated; the weight of each tablet was accurately measured separately; and the weight difference was calculated. If the number of tablets exceeding the limit was ≤2, it was considered to meet the requirements.

[0222] The test method for microbial limits is as follows: (1) Sample preparation: Take 10g of the sea buckthorn compound tablets (MH-001) prepared in Example 1, add 90mL of pH7.0 sterile sodium chloride-peptone buffer, homogenize and grind to a 1:10 test solution; serially dilute to 10 -2 10 -3 … (2) Microbial counting: Take 1 mL of each dilution and inject it into a sterile Petri dish. Immediately pour in 45-50℃ culture medium (bacteria: nutrient agar, incubate at 30-35℃ for 48h), count the colonies at 30-300 CFU / dish, and calculate the number of bacteria per 1g of test sample; ≤10 3 The CFU / g level meets the requirements.

[0223] The test results are shown in Table 1.

[0224] Table 1

[0225] Example 2: Stability Test

[0226] 1. Accelerated Experimentation

[0227] The properties and disintegration time of the sea buckthorn compound tablets (MH-001) prepared in Example 1 were observed at 0, 3 and 6 months under the conditions of temperature 40±2℃ and humidity 75±5%. The results are shown in Table 2.

[0228] Table 2

[0229] 2. Long-term experiment

[0230] Under conditions of 25±2℃ and 60±5% humidity, the properties and disintegration time of the sea buckthorn compound tablets (MH-001) prepared in Example 1 were observed at 0, 3 and 6 months. The results are shown in Table 3.

[0231] Table 3

[0232] Example 3: Animal Experiments

[0233] To investigate the pharmacodynamic effects of the sea buckthorn compound tablets (MH-001) prepared in Example 1 on a New Zealand rabbit carotid atherosclerosis model, the following animal experiments were conducted.

[0234] The following animal experiments are Non-GLP experiments, and were conducted in accordance with the "Technical Guidelines for Pharmacodynamics Research of Traditional Chinese Medicine" (July 2024) issued by the Center for Drug Evaluation of the National Medical Products Administration.

[0235] 1. Materials and Reagents

[0236] 1.1 Test substance

[0237] The sea buckthorn compound tablets (MH-001) prepared in Example 1

[0238] Storage conditions: room temperature

[0239] 1.2 Positive control

[0240] 1.2.1 Rosuvastatin Calcium Tablets (Keding)

[0241] Batch numbers: 507757, 507884, 508820

[0242] Storage conditions: Store in a tightly closed container in a dry place.

[0243] Source of commercial use: AstraZeneca (China) Co., Ltd.

[0244] 1.2.2 Tongxinluo Capsules

[0245] Batch number: B2505023

[0246] Storage conditions: Sealed

[0247] Commercially available source: Shijiazhuang Yiling Pharmaceutical Co., Ltd.

[0248] 1.3 Consumables, reagents and instruments

[0249] Table 4 Main reagents

[0250] Table 5 Main instruments

[0251] 2. Experimental system

[0252] 2.1 Experimental animals

[0253] Species and strain: New Zealand rabbits

[0254] Animal grade: Ordinary grade

[0255] Sex and quantity: Male, 75

[0256] Animal age: 3 months old (2.0 - 2.5 kg)

[0257] Source of experimental animals: Pizhou Dongfang Breeding Co., Ltd.

[0258] Production license number of experimental animals: SCXK (Su) 2022 - 0004

[0259] Animal feeding conditions and management: Ordinary grade animal room

[0260] License number for using experimental animals: SYXK (Hu) 2023 - 0001

[0261] 2.2 Reasons for selection

[0262] Reasons for selecting the species / strain of experimental animals: New Zealand rabbits are selected for this experiment because they are highly sensitive to high-fat diet, have relatively thick carotid arteries (with a diameter of about 2 - 3 mm), which is convenient for operation, and there is a large amount of preclinical experimental data available for them.

[0263] Reasons for selecting the number of animals: After comprehensively considering and meeting the objectives, scientific requirements, current scientific standards and management norms followed in the experimental protocol of this experiment, the minimum number of animals is used in this experiment. At the same time, sufficient samples are considered for data statistics when using the minimum number of animals in this experiment.

[0264] 2.3 Feeding conditions

[0265] Single-cage feeding

[0266] The animal enclosure is in a standard, well-ventilated environment.

[0267] Room temperature control: 20℃~26℃.

[0268] Relative humidity: 30%~70%.

[0269] Lighting: 12-hour alternation of light and dark.

[0270] Enriched environment: Provide enriched environment devices for laboratory animals in accordance with standard operating procedures (SOPs).

[0271] 2.4 Feed

[0272] Except in cases where fasting is required, provide qualified feed daily (Note: provide atherosclerosis model feed for model animals), and allow the animals free access to feed.

[0273] 2.5 Drinking water

[0274] During the experiment, animals had free access to drinking water (treated drinking water) supplied via water dispensers. The water bottles and stoppers were cleaned and sterilized before use.

[0275] 2.6 Adaptive Feeding

[0276] Animals underwent at least a 7-day acclimatization period before the start of drug administration (the experimental animals arrived in two batches; the first batch underwent a 7-day acclimatization period, and the second batch a 5-day acclimatization period, after which they were released following veterinary evaluation). No obvious abnormalities were observed in any of the animals during this period. The total acclimatization period (from receipt to the start of the experimental procedure) was 5-7 days.

[0277] 2.7 Animal Marking

[0278] Individual marking: Before grouping, animal identification numbers were marked and recorded using ear tags. After grouping, each animal was given a unique animal number, and a dual marking method was used to identify the animals: ① Ear tag marking, which is the primary identification mark; ② To facilitate quick differentiation of animals, the identification number was written on the animal's ear with a marker.

[0279] Cage cards: Animals were marked with cage cards used upon receiving the animals before grouping. After grouping, the experimental cage cards from the pharmacology department were used for identification.

[0280] 3 Experimental Methods

[0281] After the animals completed their acclimatization period, they were initially grouped based on body weight and baseline lipid levels, into a sham-operated group and a model group. The model group was given a high-fat diet (150 g / day) daily; the sham-operated group was given the same amount of maintenance diet daily. The date of first administration of the high-fat diet was defined as day 0. Carotid artery balloon endothelial injury surgery was performed on days 23 and 24 of high-fat diet feeding. In the sham-operated group, only the carotid artery was freed and sutured. The animals continued to be fed a high-fat diet post-surgery, and drug administration began on day 51 of high-fat diet feeding. The surgical animals were grouped according to their total cholesterol (TC) levels: model group, low-dose test drug group, medium-dose test drug group, high-dose test drug group, rosuvastatin calcium tablet group, and Tongxinluo group. Animals were administered the drug continuously for 6 weeks, and lipid levels and carotid artery ultrasound were measured at weeks 3 and 6. After drug administration, all animals were euthanized, and the common carotid artery on the operated side was fixed in formaldehyde solution (formalin) for HE staining and Masson staining.

[0282] Note: Except for the sham surgery group, animals were specially fed for approximately 7 weeks (D0-D50) after arterial injury surgery until drug treatment. After drug treatment, the special diet was halved, and the maintenance diet was increased by half (3 weeks+: D51-D76). After 3 weeks of drug treatment, the diet was adjusted to approximately 1 / 4 of the special diet and 3 / 4 of the maintenance diet (2 weeks+: D77-D94). In addition, before drug treatment, two normal animals and two animals from the model group were included to monitor blood lipid levels and the severity of the model (blood lipids were measured or ultrasound was performed at irregular intervals; samples could be collected in advance and not monitored after drug treatment).

[0283] 3.1 Group Design

[0284] Table 6 Group Design

[0285] Note: 1) Before or on the day of surgery or drug administration, if any unrelated complications occur in the grouped animals, a replacement animal of the same sex and similar weight should be selected from the remaining animals. To identify the replacement animal, its animal number will be the same as the original animal's animal number plus the letter R (e.g., 1101→1101R). The replacement animal will also be marked. Data obtained from the original animal will be stored in the original data set but not reported; only the results from the replacement animal will be reported.

[0286] 2) Due to the uncertainty of the experimental surgery and the individual differences among animals, 1-2 rabbits can be reserved for each group.

[0287] 3) If the animal dies or is near death during the administration period, it may be decided whether to take samples (carotid artery) or organs (such as liver, kidney, etc.) for preservation, depending on the actual situation.

[0288] 4) The dosage mg / kg refers to the mass of sea buckthorn compound tablets (MH-001) given to each kilogram of animal.

[0289] 3.1.1 Feeding with special feed (atherosclerosis model feed)

[0290] After the initial grouping of animals, except for the sham-operated group (including reserve animals), other animals were fed an atherosclerosis model diet (approximately 150 g / day). After 3-4 weeks of continuous feeding (D0-D22), balloon endothelial injury surgery was performed. Post-surgery, the model group animals continued to be fed the atherosclerosis model diet for approximately 3-4 weeks (the sham-operated group received only a normal maintenance diet; D23-D50). Once the model group animals were fully grouped, the drug treatment phase began. For the first 3 weeks of drug treatment, except for the sham-operated group, the special diet for other groups was halved, and the maintenance diet was increased by half (3 weeks+: D51-D76); thereafter, feeding continued for 2-3 weeks, adjusting to approximately 1 / 4 special diet and 3 / 4 maintenance diet (2 weeks+: D77-D94).

[0291] 3.1.2 Carotid balloon endothelial injury surgery

[0292] The patient should fast for approximately 6-20 hours prior to surgery, but water intake is permitted. Preoperative anesthesia is administered via subcutaneous injection of meloxicam (0.2 mg / kg) and via intravenous or intramuscular injection of a mixture of 10-20 mg / kg of acetaminophen and 3-8 mg / kg of xylazine. The patient is then placed in a supine position and fixed on the operating table. A longitudinal incision is made along the midline of the neck. The tissues and muscles are bluntly dissected layer by layer above the thyroid cartilage to expose the right common carotid artery. A segment of the common carotid artery approximately 2 cm long is isolated. Arterial clamps are used to sequentially clamp the proximal ends of the common carotid artery, internal carotid artery, and external jugular vein. A slipknot is placed at the proximal end of the external carotid artery, and the distal end is tightly ligated. A balloon catheter (2 mm in diameter) is inserted into the external carotid artery against the direction of blood flow from the common carotid artery. 0.05-0.1 mL of normal saline is injected to inflate the balloon, which is then slowly pulled back to the bifurcation point between the common carotid and external carotid arteries. The fluid in the balloon is aspirated to reduce the pressure to zero, and the balloon is reinserted. This process is repeated three times. When there is resistance during pullback, it indicates that the balloon diameter is anastomosed with the blood vessel. Withdraw the balloon, tighten the suture at the proximal end of the external carotid artery with a slipknot, remove the arterial clamp from the internal carotid artery first, then remove the arterial clamp at the proximal end of the common carotid artery, restore arterial blood flow, compress to stop bleeding, suture the wound, and apply crystalline sulfanilamide powder and povidone-iodine to the wound. Postoperatively, apply povidone-iodine to the wound, and administer subcutaneous injections of ceftriaxone sodium (25-50 mg / kg) in the chest and back to prevent infection, once daily for 5 consecutive days. Postoperative analgesia (meroxetine: 0.2 mg / kg, subcutaneous injection) is administered once daily for 5 days of continuous observation.

[0293] 3.1.3 Drug intervention therapy

[0294] After the animals were grouped, they were administered the drugs according to Table 6, once daily for 6 consecutive weeks (D51-D94).

[0295] Both the sham surgery group and the model group were given pure water. The low, medium, and high dose groups of the test substance were given sea buckthorn compound tablets (MH-001) (75 mg / kg, 150 mg / kg, and 300 mg / kg, respectively). The rosuvastatin calcium tablet group and the Tongxinluo group were administered at doses of 1 mg / kg and 150 mg / kg, respectively.

[0296] 3.2 Animal Grouping

[0297] A total of 56 animals were enrolled, with 8 animals per group. One to two animals can be kept as spares per group, depending on the actual situation.

[0298] Table 7 Animal Grouping and Numbering

[0299] 3.3 Animal administration

[0300] Route of administration: Gavage.

[0301] Administration site: Oral gavage.

[0302] Dosage frequency: once daily.

[0303] Administration method: Administer the medication by bolus injection using a suitable syringe. Calculate the dosage per animal at a volume of 5 mL / kg.

[0304] Reason for choosing the route of administration: to select a route of administration similar to that intended for clinical use.

[0305] 3.4 Inspection Indicators

[0306] 3.4.1 General Observation

[0307] Adaptation period: All animals were observed at least once before being grouped.

[0308] Special feeding, surgery, and medication periods: at least once a week.

[0309] Terminal sampling period: Surviving animals enrolled in the group were observed at least once before euthanasia.

[0310] The observations include the number of animals, their survival status (e.g., alive, dead, or near death), and the availability of food and water. The frequency of observations can be increased or decreased as needed for the experiment.

[0311] 3.4.2 Weight

[0312] Adaptation period: All animals were weighed at least once before being grouped.

[0313] Special feeding, surgery, and medication periods: at least once a week.

[0314] Terminal sampling period: Surviving animals enrolled in the group were weighed once before euthanasia. If the weight was only used to calculate the dosage of anesthesia, no statistical analysis was required.

[0315] All animals included in the group must be weighed once if they are found to be dead or near death and euthanized.

[0316] 3.4.3 Blood lipid level testing

[0317] 1) Sample collection

[0318] Animals collected: Groups 1-7 (animals were collected after fasting but not watering for 12-16 hours).

[0319] Blood collection sites: middle auricular artery or jugular vein

[0320] Sampling time points: See Table 8 below for sample collection time points.

[0321] Table 8

[0322] Collection volume: 0.5~1.0 mL

[0323] Sampling tube: 3.5 mL coagulation accelerator tube; 2) Sample handling For testing: Take 0.5-1.0 mL of whole blood into a coagulation tube, leave at room temperature for about 0.5-1 hour, centrifuge for 10 minutes (4000 rpm, 22℃), collect the supernatant, and store at -80±10℃ for later testing. This procedure should be completed within 2 hours after blood collection.

[0324] 3) Detection and Analysis

[0325] Detects TG, TC, LDL-C, and HDL-C.

[0326] 3.4.4 Blood rheology testing

[0327] 1) Sample collection

[0328] Animals collected: Groups 1-7 (animals were collected after fasting but not watering for 12-16 hours).

[0329] Blood collection sites: jugular vein or abdominal aorta

[0330] Sampling time points: See Table 9 below for sample collection time points.

[0331] Table 9

[0332] Collection volume: 3.0 mL or 5.0 mL

[0333] Sampling tube: 3.0 mL or 5.0 mL heparin sodium anticoagulant tube

[0334] 2) Sample handling

[0335] For testing: Take 3.0 mL or 5.0 mL of whole blood into a heparin anticoagulant tube (add heparin in advance), immediately invert and mix at least 5 times, being careful with the animal to avoid hemolysis and clot formation. Store at room temperature and complete the test within 4 hours of sampling.

[0336] 3) Detection and Analysis

[0337] The viscosity of anticoagulated blood was directly measured using a fully automated hemorheology analyzer.

[0338] 3.4.5 Blood biochemical index testing

[0339] 1) Sample collection

[0340] Animals collected: Groups 1-7 (animals were collected after fasting but not watering for 12-16 hours).

[0341] Blood collection sites: middle auricular artery or jugular vein

[0342] Sampling time points: See Table 10 below for sample collection time points.

[0343] Table 10

[0344] Collection volume: 1.0 mL can be used for blood lipid level testing; the blood collection volume at the treatment endpoint is increased by 1.0 mL (to increase the detection of heart, liver and kidney function indicators).

[0345] Sampling tube: 3.5 mL coagulation tube

[0346] 2) Sample handling

[0347] For testing: Take 1.0 mL of whole blood into a coagulation tube, incubate at room temperature for about 0.5-1 hour, centrifuge for 10 minutes (4000 rpm, 22℃), collect the supernatant, and store at -80±10℃ for later testing. This procedure should be completed within 2 hours after blood collection.

[0348] 3) Detection and Analysis

[0349] Serum SOD and MDA are detected using reagent kits.

[0350] The following additional testing indicators were added to the treatment endpoint: Liver function tests: alanine aminotransferase (ALT), aspartic aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatine kinase (CK), total protein (TP), albumin (ALB), blood glucose (GLU), and total bilirubin (TBil).

[0351] Kidney function: Urea, Creatinine.

[0352] 3.4.6 Coagulation panel test

[0353] 1) Sample collection

[0354] Animals collected: Groups 1-7 (animals were collected after fasting but not watering for 12-16 hours).

[0355] Blood collection site: jugular vein

[0356] Sampling time points: See Table 11 below for sample collection time points.

[0357] Table 11

[0358] Collection volume: 0.9 mL

[0359] Sampling tube: 1.0 mL sodium citrate anticoagulant tube

[0360] 2) Sample handling

[0361] For testing: Take 0.9 mL of whole blood and place it in an anticoagulant tube containing sodium citrate. Invert the tube to mix well and allow it to cool to room temperature. Send the tube to the clinical laboratory as soon as possible.

[0362] 3) Detection and Analysis

[0363] The test measures prothrombin time (PT), activated partial thromboplastin time (PTT), and fibrinogen (FIB).

[0364] 3.4.7 Ultrasonic Testing

[0365] Ultrasound examinations were performed at the following times: before feeding with the special feed (atherosclerosis model feed) on D-3, before surgical injury (3-4 weeks of feeding with the special feed) on D18, 3-4 weeks after surgical injury (before treatment administration) on D50, 3 weeks after treatment administration on D73, and 6 weeks after treatment administration on D88.

[0366] Procedure: After anesthetizing the animals (using a mixture of ketamine 22-50 mg / kg and xylazine 2-10 mg / kg via marginal ear vein or intramuscular injection; or a mixture of salbutamol 10-20 mg / kg and xylazine 3-8 mg / kg via marginal ear vein or intramuscular injection), the neck hair was shaved, the rabbit's neck was cleaned, and then coupling gel was applied to the neck skin. A Doppler ultrasound system (M9Vet, Mindray) was used for examination. The carotid intima-media thickness (IMT), luminal diameter, and blood flow velocity were measured and compared.

[0367] 3.4.8 Auricular microcirculation detection

[0368] Auricular microcirculation was detected on day 91 after treatment administration.

[0369] Operating procedure: Animals were anesthetized (via intravenous or intramuscular injection of a mixture of 10-20 mg / kg of acetaminophen and 3-8 mg / kg of xylazine). A laser speckle flow monitoring system was used to detect the microcirculation status of the auricle. Equipment settings were as follows: Camera parameters (exposure time 3ms; Sliding mode: spatial algorithm, 2048×2048); magnification (0.6); recording mode (continuous recording, duration 3s); pseudo-color threshold (low perfusion 70; high perfusion 200); view selection (real image, grayscale image, speckle image (specimen image display only in online mode), pseudo-color image); grid adjustment (12×12). Light intensity settings (laser intensity: 80 mW; white light intensity: level 1).

[0370] 3.4.9 Tongue observation

[0371] Tongue appearance was observed during treatment administration of D88.

[0372] Procedure: Anesthetize the animal (inject a mixture of 10-20 mg / kg of salbutamol and 3-8 mg / kg of xylazine via the ear vein or intramuscularly), pull out the rabbit's tongue, and take a picture of the underside of the tongue with a Sony DSC-H300 digital camera to observe whether there are any abnormalities in the tongue coating (such as thick tongue coating, tortuous veins, etc.).

[0373] 3.4.10 Pathological Examination

[0374] Six weeks after treatment, animals were anesthetized by intravenous or intramuscular injection of a mixture of 10-20 mg / kg of salbutamol and 3-8 mg / kg of xylazine. The carotid artery was then harvested, fixed in formalin, and stained with hematoxylin and eosin (HE) and Masson stain, respectively.

[0375] HE: Routine HE staining and slide reading.

[0376] Masson staining: Perform the procedure according to the Masson staining kit instructions. Under a light microscope, collagen fibers are stained blue or green, muscle fibers are red, and cell nuclei are dark blue. ImageJ image analysis software can be used for quantitative analysis of the staining results.

[0377] Image analysis software was used to statistically analyze the intima thickness, medial lining thickness, intima cross-sectional area, and lumen area, and to calculate the intima-media thickness ratio and intima area ratio.

[0378] Intima area ratio (%) = (Intima cross-sectional area / (Intima cross-sectional area + Lumen area)) × 100%

[0379] Remark: 1) At the endpoint, the carotid artery was taken for HE and Masson staining.

[0380] 2) At the end of the process, another blood vessel will be taken from the aortic arch, thoracic aorta, abdominal aorta to the bifurcation of the iliac artery, and fixed in formalin for later use.

[0381] 3) Perform HE and Masson staining on the common carotid artery.

[0382] 3.4.11 Liver TC / TG Detection

[0383] At the endpoint of animal drug treatment, an appropriate amount of liver tissue (abbreviated) was taken and frozen at -80±10℃ for later use (the supernatant of the tissue homogenate was used to detect TC / TG).

[0384] The overall testing indicators are summarized in Table 12 below: Table 12

[0385] Remark: 1) X indicates that the corresponding indicator needs to be detected at this time point.

[0386] 2) Increase the blood biochemistry endpoint by 1.0 mL and test cardiac, liver and kidney function indicators.

[0387] 3) / indicates that the item is not tested.

[0388] 3.5 Animal terminal disposal

[0389] 3.5.1 Animal Disposal at the End of the Process

[0390] According to the AVMA Guidelines for the Euthanasia of Animals: 2020 Edition (the American Veterinary Medical Association, 2020) and the corresponding SOPs, all surviving animals enrolled in the study were anesthetized at the end of the experiment by intravenous or intramuscular injection of a mixture of 10-20 mg / kg of salbutamol and 5-10 mg / kg of xylazine, followed by euthanasia via exsanguination of the abdominal aorta using physical methods. Animals undergoing euthanasia in a dying state were euthanized using the same methods as those undergoing planned euthanasia.

[0391] 3.6 Statistical Analysis

[0392] Experimental data are expressed as mean ± standard error (mean ± SEM). Data were analyzed using Excel or GraphpadPrism with appropriate statistical methods. P < 0.05 was considered statistically significant.

[0393] 4. Experimental Results

[0394] 4.1 General Observation

[0395] A total of 75 rabbits were purchased for the experiment. They were observed at least once a week during the experiment, and the animals were in good overall condition.

[0396] Before animal enrollment, one rabbit (A0862) exhibited loose stools and hind limb paralysis and was subsequently euthanized. Before carotid artery surgery: One rabbit (A0809) in the model group was found to be underweight, eating poorly, and in poor condition 3 weeks after modeling, with a weight approximately 20% below the average weight of model animals; therefore, it was excluded from surgery. During surgery (before drug administration and enrollment): Three model rabbits (A0854, A0845, A0806) died during surgery and care; two model rabbits (A0884, A0844) were euthanized due to allergic hair loss. During the administration period: In the low-dose group, subject 3108 (identification number A0815) died on D94 (January 29, 2026) due to administration procedure error; in the medium-dose group, subject 4103 (A0877) died on D61 (December 27, 2025) due to jaundice, and subject 4104 (A0813) died approximately 1 hour after administration on D83 (January 18, 2026), with autopsy revealing possible lung abnormalities; in the rosuvastatin calcium tablet group, subjects 6101 (A0871) and 6105 (A0870) died on D63 (December 29, 2025) due to jaundice; subject 6103 (A0860) died on D67 (January 2, 2026) (body weight decreased by 0.5 kg in one week prior to death). kg); 6104 (A0830) was euthanized on D74 (2026.01.09) due to jaundice; Tongxinluo group 7105 (A0869) died on D74 (2026.01.09) due to jaundice.

[0397] 4.2 Weight

[0398] As shown in Table 13, D-4 represents the animal's body weight before being fed a special diet (high-fat diet); D0 represents the start of feeding on a completely special diet (high-fat diet); D23 and D24 represent carotid artery balloon injury surgery; D51 represents the first day of administration (administration D0); D72 represents 3 weeks of administration (administration D21); and D93 represents 6 weeks of administration (administration D42). After administration, the animals' body weight grew normally over time; at each corresponding time point, there was no significant difference in animal body weight between the groups.

[0399] Table 13 Effects of test substances on animal body weight (mean ± SEM)

[0400] 4.3 Blood lipid level testing

[0401] As shown in Table 14, after approximately 7 weeks of high-fat diet before administration (D46), the blood lipid levels (CHO, TG, HDL, LDL) in the model group were significantly higher than those in the sham-operated group (P<0.01); compared with the rosuvastatin group, the HDL level in the low-dose test substance group was significantly higher (P<0.05); there were no significant differences in blood lipid levels (CHO, TG, LDL) among the model group and other administration groups. As shown in Table 15, after 3 weeks of administration (high-fat diet on D70), the blood lipid levels (CHO, TG, HDL, LDL) in the model group were significantly higher than those in the sham-operated group (P<0.01); compared with the model group, HDL levels in the low-dose test substance group and the rosuvastatin calcium tablet group were significantly increased (P<0.05), and the LDL level in the rosuvastatin calcium tablet group was also significantly higher than that in the model group (P<0.05); there were no significant differences in blood lipid levels among the three dosage groups of the test substance compared with rosuvastatin or Tongxinluo. As shown in Table 16, after 6 weeks of drug administration (D94), the lipid levels (CHO, TG, HDL, LDL) in the model group were significantly higher than those in the sham-operated group (P<0.01). Compared with the model group, HDL levels in the low-dose test substance group and the rosuvastatin calcium tablet group were significantly increased (P<0.05), and HDL levels in the Tongxinluo group were significantly increased (P<0.01). Compared with the Tongxinluo group, HDL levels in the medium-dose group and the high-dose group were significantly decreased (P<0.05). LDL levels in the low-dose test substance group were significantly higher than those in the model group (P<0.05).

[0402] Table 14. Blood lipid levels (mean ± SEM) of rabbits in each group before drug administration (D46).

[0403] Remark: P<0.01 vs. sham surgery group; & P<0.05 vs. rosuvastatin calcium tablet group.

[0404] Table 15 Effect of test substance on blood lipid levels in rabbits after 3 weeks of administration (D70) (mean±SEM)

[0405] Remark: P<0.01 vs. sham surgery group; #P<0.05 vs. model group.

[0406] Table 16 Effect of test substance on blood lipid levels in rabbits after 6 weeks of administration (D94) (mean±SEM)

[0407] Remark: P<0.01 vs. sham surgery group; #P<0.05 vs. model group; ##P<0.01 vs. model group; $P<0.05 vs. Tongxinluo group.

[0408] 4.4 Blood rheology testing

[0409] As shown in Table 17, venous blood was collected 6 weeks after drug administration (D92) at different shear rates (1s). -1 5s -1 11.5s -1 50s -1 115s -1 200s -1 Blood viscosity was measured under the following conditions: shear rate 1s. -1 Under these conditions, there was no significant difference between the sham surgery group and the model group (P>0.05); the viscosity of the low-dose and medium-dose groups of the test substance was significantly higher than that of the model group, rosuvastatin calcium tablet group, and Tongxinluo group (P<0.01); the viscosity of the high-dose group was significantly lower than that of the low- and medium-dose groups (P<0.01); the viscosity of the medium-dose group was significantly lower than that of the low-dose group (P<0.01). At a shear rate of 5s... -1 Under these conditions, the whole blood viscosity in the model group was significantly higher than that in the sham-operated group (P<0.05); the viscosity in the low-dose and medium-dose groups of the test substance was significantly higher than that in the model group, rosuvastatin calcium tablet group, and Tongxinluo group (P<0.01); the viscosity in the medium-dose group was significantly lower than that in the low-dose group (P<0.01); and the viscosity in the high-dose group was significantly lower than that in the low- and medium-dose groups (P<0.01). At a shear rate of 11.5 s⁻¹... -1 Under these conditions, there was no significant difference between the sham-operated group and the model group (P>0.05); the viscosity of the low-dose and medium-dose groups of the test substance was significantly higher than that of the model group, rosuvastatin calcium tablet group, and Tongxinluo group (P<0.01); the high-dose group was significantly higher than that of the model group (P<0.05); the viscosity of the high-dose group was significantly lower than that of the low- and medium-dose groups (P<0.01); the viscosity of the medium-dose group was significantly lower than that of the low-dose group (P<0.01). At a shear rate of 50 s⁻¹... -1 Under these conditions, the whole blood viscosity in the model group was higher than that in the normal group (P=0.0525). Compared with the model group, the viscosity of the low-dose and medium-dose groups of the test substance was significantly increased (P<0.01); the viscosity of the high-dose and Tongxinluo groups was significantly increased (P<0.05); the viscosity of the low-dose group was significantly higher than that of the rosuvastatin group and the Tongxinluo group (P<0.01); the viscosity of the medium-dose group was significantly lower than that of the low-dose group (P<0.05); and the viscosity of the high-dose group was significantly lower than that of the low-dose group (P<0.01). At a shear rate of 115 s⁻¹... -1 Under these conditions, the whole blood viscosity in the model group was significantly higher than that in the normal group (P<0.05); compared with the model group, the viscosity of the low-dose group of the test substance was significantly increased (P<0.01); the viscosity of the medium-dose group was significantly increased (P<0.05); the viscosity of the low-dose group was significantly higher than that of the rosuvastatin group and the Tongxinluo group (P<0.05); and the viscosity of the high-dose group was significantly lower than that of the low-dose group (P<0.05). At a shear rate of 200 s⁻¹... -1Under the given conditions, the whole blood viscosity in the model group was significantly higher than that in the normal group (P<0.05); compared with the model group, the viscosity in the low-dose test substance group was significantly increased (P<0.01); there were no significant differences among the other groups.

[0410] Overall, rosuvastatin had no significant effect on whole blood viscosity under various shear rates. Both high-dose sea buckthorn compound tablets MH-001 and Tongxinluo increased whole blood viscosity at a specific shear rate (50 / sec); however, overall, the high-dose sea buckthorn compound tablets MH-001 and Tongxinluo had comparable effects under various shear rates. The viscosity of the high-dose group of sea buckthorn compound tablets MH-001 was lower than that of the low- and medium-dose groups under different shear rates.

[0411] Table 17 Effects of the test substance on hemorheology after 6 weeks of administration (D92) (mean±SEM)

[0412] Remark: P<0.05 vs. sham surgery group; #P<0.05 vs. model group; ##P<0.01 vs. model group; &P<0.05 vs. rosuvastatin calcium tablet group; &&P<0.01 vs. rosuvastatin calcium tablet group; $P<0.05 vs. Tongxinluo group; $$P<0.01 vs. Tongxinluo group; aP<0.05 vs. low-dose group; aaP<0.01 vs. low-dose group; bbP<0.01 vs. medium-dose group.

[0413] 4.5 Blood biochemical index testing

[0414] 4.5.1 Blood SOD and MDA Detection

[0415] As shown in Table 18, there were no significant differences in SOD activity among the groups after 3 weeks of administration (D70). After 6 weeks of administration (D94), the SOD activity in the model group was significantly lower than that in the sham-operated group (P<0.01), while there were no significant differences in SOD activity between the model group and the other administration groups. After 3 weeks of administration, the MDA in the model group was significantly higher than that in the sham-operated group (P<0.01). Compared with the model group, the MDA in the high-dose group was significantly lower (P<0.05), and both the rosuvastatin and Tongxinluo groups were significantly lower (P<0.01). Compared with the rosuvastatin and Tongxinluo groups, the MDA in the low-dose group was significantly higher (P<0.01). The MDA in the medium-dose group was significantly higher than that in the rosuvastatin group (P<0.05) and significantly higher than that in the Tongxinluo group (P<0.01). The MDA in the high-dose group was significantly lower than that in the low-dose group (P<0.01). After 6 weeks of administration, the MDA level in the model group was significantly higher than that in the sham surgery group (P<0.01); there were no significant differences between the other administration groups and the model group; the MDA level in the low-dose group was significantly higher than that in the Tongxinluo group (P<0.05); and the MDA level in the high-dose group was significantly lower than that in the low-dose and medium-dose groups (P<0.05).

[0416] Table 18 Effects of the test substance on SOD and MDA at 3 and 6 weeks of administration (mean±SEM)

[0417] Remark: P<0.01 vs. sham surgery group; #P<0.05 vs. model group; ##P<0.01 vs. model group; &P<0.05 vs. rosuvastatin calcium tablet group; &&P<0.01 vs. rosuvastatin calcium tablet group; $P<0.05 vs. Tongxinluo group; $$P<0.01 vs. Tongxinluo group; aP<0.05 vs. low-dose group; aaP<0.01 vs. low-dose group; bP<0.05 vs. medium-dose group.

[0418] 4.5.2 Cardiac / Liver / Kidney Function Tests

[0419] As shown in Table 19, the effects of the test substance on liver and kidney biochemical indicators were detected by collecting venous blood samples after 6 weeks of drug administration (D94): Regarding liver function: ALB (albumin) in the model group was significantly lower than that in the sham-operated group (P<0.01); there were no significant differences between the model group and each treatment group; compared with the rosuvastatin calcium tablet group, the low-dose test substance group was significantly lower (P<0.05). Compared with the sham-operated group, there was no significant difference in GGT (glutamin transferase) in the model group; Compared with the model group, the rosuvastatin calcium tablet group showed a significant increase in GGT (P<0.01); compared with the rosuvastatin group, the low-dose and medium-dose groups showed a significant decrease in GGT (P<0.01), and the Tongxinluo group showed a significant decrease (P<0.05). The model group had significantly lower GLU (glucose) than the sham-operated group (P<0.01), with no significant difference between the model group and other treatment groups. The model group had significantly higher TBil (total bilirubin) than the sham-operated group (P<0.01); with no significant difference between the model group and other treatment groups. Compared with the sham-operated group, the model group had no significant difference in TP (total protein); compared with the model group, the rosuvastatin group showed a significant increase in TP (P<0.01); compared with the rosuvastatin group, the high-dose group showed a significant decrease in TP (P<0.05), and the low-dose, medium-dose, and Tongxinluo groups showed significant decreases (P<0.01). Compared with the sham-operated group, the model group showed an increasing trend in ALT (alanine aminotransferase), but the difference was not statistically significant; there was no significant difference between the model group and each treatment group; compared with the rosuvastatin group, the low-dose group of the test substance was significantly lower (P<0.05). Compared with the sham-operated group, the model group showed no significant difference in AST (aspartate aminotransferase); compared with the model group, the rosuvastatin group showed a significant decrease in AST (P<0.05); compared with the rosuvastatin group, the low-dose and medium-dose groups of the test substance were significantly lower (P<0.05). Compared with the normal group, the model group showed no significant difference in ALP (alkaline phosphatase); there was no significant difference between the model group and each treatment group. Compared with the sham surgery group, the model group showed a significant increase in CK (creatine kinase) (P<0.05); compared with the model group, the medium-dose group (P=0.0698) and the Tongxinluo group (P=0.0904) showed a decreasing trend in CK; compared with the rosuvastatin group, the medium-dose group and the Tongxinluo group showed a significant decrease (P<0.05); compared with the Tongxinluo group, the high-dose group showed a significant increase in CK (P<0.05); the high-dose group had a significantly higher CK than the medium-dose group (P<0.05).

[0420] Regarding renal function: Compared with the sham-operated group, the model group showed an increasing trend in urea (urea), but the difference was not statistically significant; there was no significant difference between the model group and each treatment group. Compared with the sham-operated group, the model group showed no significant difference in creatinine (CRE); there was no significant difference between the model group and each treatment group; compared with rosuvastatin, the low-dose group and the Tongxinluo group showed significantly lower CRE (P<0.05).

[0421] Table 19-1 Effects of the test substance on liver and kidney biochemical parameters after 6 weeks of administration (D94) (mean±SEM)

[0422] Table 19-2 Effects of the test substance on liver and kidney biochemical parameters after 6 weeks of administration (D94) (mean±SEM)

[0423] Remark: P<0.05 vs. sham surgery group; P<0.01 vs. sham surgery group; #P<0.05 vs. model group; ##P<0.01 vs. model group; &P<0.05 vs. rosuvastatin calcium tablet group; &&P<0.01 vs. rosuvastatin calcium tablet group; $P<0.05 vs. Tongxinluo group; bP<0.05 vs. medium dose group.

[0424] 4.6 Coagulation panel test

[0425] As shown in Table 20, compared with the sham surgery group, the prothrombin time (PT) in the model group was significantly prolonged (P<0.01), contrary to expectations; compared with the model group, the PT in the rosuvastatin group was significantly shortened (P<0.05); there were no significant differences in other treatment groups. Compared with the sham surgery group, the activated partial thromboplastin time (APTT) in the model group was decreased, but the difference was not significant; compared with the model group, the APTT in the rosuvastatin group was significantly prolonged (P<0.05); compared with the rosuvastatin group, the APTT in the medium-dose and high-dose groups of the test substance was significantly shortened (P<0.05).

[0426] Compared with the sham surgery group, the fibrinogen level in the model group was significantly lower (P<0.01), contrary to expectations; compared with the model group, there was no significant difference in fibrinogen level among the drug administration groups; compared with the Tongxinluo group, the fibrinogen level in the high-dose group of the test substance was significantly higher (P<0.05).

[0427] Table 20 Effect of test substance on coagulation function after 6 weeks of administration (D92) (mean ± SEM)

[0428] Remark: P<0.01 vs. sham surgery group; #P<0.05 vs. model group; &P<0.05 vs. rosuvastatin calcium tablet group; $P<0.05 vs. Tongxinluo group.

[0429] 4.7 Ultrasonic Testing

[0430] In ultrasound examinations, the four indicators of interest are PS (peak systolic velocity), ED (end diastolic velocity), Dm (mean diameter of the vessel lumen), and IMT (intima-media thickness). In atherosclerosis (AS) models, PS, ED, and Dm are usually reduced, while IMT is usually increased.

[0431] In pathological examination, the intima thickness, media thickness, intima-media thickness ratio, and intima cross-sectional area / intima area + lumen area that are of interest are usually reflected in AS as follows: the intima thickness is thickened, the media thickness is thinned, the intima-media thickness ratio is increased, and the intima cross-sectional area / intima area + lumen area is increased.

[0432] 3 weeks after administration: As shown in Table 21, medium and high doses of sea buckthorn compound tablets (MH-001) significantly affected blood flow velocity, significantly increasing PS (medium dose: P<0.05 vs. model group; high dose: P<0.01 vs. model group) and ED (medium dose: P<0.05 vs. model group; high dose: P<0.01 vs. model group); rosuvastatin significantly increased PS (P<0.05 vs. model group), but had no effect on ED; Tongxinluo significantly increased ED (P<0.01 vs. model group), but had no effect on PS; PS in the high-dose group was significantly higher than that in the low-dose group (P<0.05); compared with the Tongxinluo group, ED in the low-dose group was significantly reduced (P<0.05).

[0433] Regarding the lumen diameter (Dm), high-dose sea buckthorn compound tablets (MH-001) (P<0.01 vs model group), rosuvastatin (P<0.05 vs model group), and Tongxinluo (P<0.05 vs model group) all significantly increased the lumen diameter; the lumen diameter Dm of the high-dose group was significantly greater than that of the low-dose group and the medium-dose group (P<0.05).

[0434] Regarding intima-media thickness (IMT), high-dose sea buckthorn compound tablets (MH-001) (P<0.01 vs model group), rosuvastatin (P<0.01 vs model group), and Tongxinluo (P<0.05 vs model group) all significantly reduced intima-media thickness; the intima-media thickness in the high-dose group was significantly lower than that in the low-dose group (P<0.05) and the medium-dose group (P<0.01).

[0435] 6 weeks after administration: As shown in Table 22, the high dose of sea buckthorn compound tablets (MH-001) significantly increased PS (P<0.05 vs. model group), while rosuvastatin and Tongxinluo had no significant effect on PS; the high dose of sea buckthorn compound tablets (MH-001) significantly increased ED (P<0.05 vs. model group), Tongxinluo also significantly increased ED (P<0.01 vs. model group), while rosuvastatin had no significant effect on ED.

[0436] Regarding the lumen diameter (Dm), sea buckthorn compound tablets (MH-001) significantly increased the carotid artery lumen diameter at medium doses (P<0.05 vs. model group), while at high doses, there was a tendency to increase it; Tongxinluo also significantly increased the lumen diameter (P<0.05 vs. model group), while rosuvastatin had no significant effect.

[0437] No significant effect was observed in any dose group of sea buckthorn compound tablets (MH-001), rosuvastatin, or Tongxinluo on intima-media thickness (IMT).

[0438] Table 21 Effects of the test substance on carotid ultrasound after 3 weeks of administration (D73) (mean±SEM)

[0439] Remark: P<0.01 vs. sham surgery group; #P<0.05 vs. model group; ##P<0.01 vs. model group; &P<0.05 vs. rosuvastatin calcium tablet group; $P<0.05 vs. Tongxinluo group; aP<0.05 vs. low-dose group; bP<0.05 vs. medium-dose group; bbP<0.01 vs. medium-dose group.

[0440] Table 22 Effects of the test substance on carotid ultrasound after 6 weeks of administration (D88) (mean±SEM)

[0441] Remark: P<0.05 vs. sham surgery group; P<0.01 vs. sham surgery group; #P<0.05 vs. model group; ##P<0.01 vs. model group.

[0442] 4.8 Auricular microcirculation detection

[0443] As shown in Table 23, there was no significant difference in blood perfusion volume between the model group and the normal group; there was no significant effect in the other drug administration groups compared with the model group.

[0444] Table 23 Effects of the test substance on auricular microcirculation after 6 weeks of administration (D91) (mean±SEM)

[0445] 4.9 Tongue observation

[0446] As shown in Table 24, the tongue observation results indicated that the tongue surface color of rabbits in each group was normal, and no abnormal vascular tortuosity was observed. White spots or patches appeared on the tongue surface of some animals. The results are summarized in the following table, based on the number of animals with white spots / total number of animals in each group: In the model group, 75% of the animals developed white spots or lumps, and neither high-dose sea buckthorn compound tablets (MH-001) nor rosuvastatin showed any improvement. However, after administration of Tongxinluo, only 25% of the animals developed white spots or lumps.

[0447] Table 24

[0448] 4.10 Pathological examination

[0449] After carotid artery pathological staining, subjective scores were assigned to five indicators regarding the degree of luminal obstruction, the degree of internal elastic lamina rupture, the degree of collagen fibrosis, the degree of intimal thickening, and the degree of medial atrophy, as shown in Table 25. Compared with the sham surgery group, the pathological scores of the model group were significantly higher than those of the sham surgery group (P<0.01 vs sham surgery). After administration of the corresponding treatment drugs, the following was observed: Regarding the degree of luminal obstruction, sea buckthorn compound tablets (MH-001) tended to reduce pathological scores at various doses, and Tongxinluo also showed a similar trend; while rosuvastatin did not show this trend.

[0450] Regarding the degree of internal elastic membrane rupture, sea buckthorn compound tablets (MH-001) significantly improved the degree of rupture at medium and high doses (P<0.05 vs model group); the improvement in the degree of internal elastic membrane rupture in the medium and high dose groups was significantly higher than that in the low dose group (P<0.05); rosuvastatin and Tongxinluo only showed an improvement trend.

[0451] Regarding the degree of collagen fibrosis, only rosuvastatin showed a trend of improvement.

[0452] For the degree of intimal thickening, high-dose sea buckthorn compound tablets (MH-001) and Tongxinluo showed a trend of improvement.

[0453] Regarding the degree of tunica media atrophy, there was no significant improvement trend in any of the treatment groups compared with the model group; compared with the Tongxinluo group, the tunica media atrophy was significantly greater in the medium-dose group and the high-dose group (P<0.05).

[0454] Table 25 Carotid artery pathology score (mean ± SEM)

[0455] Remark: P<0.01 vs. sham surgery group; #P<0.05 vs. model group; $P<0.05 vs. Tongxinluo group; aP<0.05 vs. low-dose group.

[0456] In addition, image analysis software was used to statistically analyze the intima-media thickness, intima-media cross-sectional area, and lumen area of ​​the carotid artery, and to calculate the intima-media thickness ratio and the ratio of intima-media cross-sectional area to intima-media area plus lumen area.

[0457] As shown in Table 26, the carotid intima thickness, intima-media thickness ratio, and intima area / intima + lumen area ratio were significantly increased in the model group animals, while the media thickness was significantly decreased.

[0458] When the test substance, sea buckthorn compound tablets (MH-001), was administered, it significantly reduced the ratio of intima-media thickness and the ratio of intima area / intima + lumen area at medium and high doses (P<0.05 vs. model group), suggesting that sea buckthorn compound tablets (MH-001) can improve the degree of luminal obstruction. At high doses, sea buckthorn compound tablets (MH-001) significantly increased the thickness of tunica media smooth muscle, while showing a certain decreasing trend in intima thickness. Compared with the low-dose group, the high-dose group showed a significant increase in tunica media thickness (P<0.05), while the ratio of intima-media thickness was significantly decreased in the medium- and high-dose groups (P<0.05).

[0459] When rosuvastatin was administered, it only showed a decreasing trend in intimal thickness, the intimal-media thickness ratio, and the ratio of intimal area to intimal + lumen area, while it only showed a slight increasing trend in media smooth muscle thickness.

[0460] When Tongxinluo was administered, it significantly reduced the intima-media thickness ratio (P<0.05 vs. model group), while it only showed a decreasing trend in the ratio of intima thickness to intima area / intima + lumen area, and only an increasing trend in the thickness of tunica media smooth muscle.

[0461] Table 26. Statistical analysis of carotid artery pathological parameters (mean±SEM)

[0462] Remark: P<0.01 vs. sham surgery group; #P<0.05 vs. model group; $P<0.05 vs. Tongxinluo group; aP<0.05 vs. low-dose group.

[0463] 5. Discussion and Conclusion

[0464] The potential therapeutic effects of sea buckthorn compound tablets (MH-001) were investigated in a rabbit model of carotid artery atherosclerosis induced by a high-fat diet combined with balloon injury, and compared with rosuvastatin and Tongxinluo. Based on the existing data, the following preliminary conclusions can be drawn: 1) Model preparation: Using a high-fat diet containing 1% cholesterol and 5% lard, the diet consisted of 7 weeks of full high-fat diet, 3 weeks of approximately 1 / 2 high-fat diet, and 2 weeks of approximately 1 / 4 high-fat diet. Carotid artery balloon injury model was established after 23 days of full high-fat diet combined with vitamin D supplementation. Before drug administration, and at 3 and 6 weeks after drug administration, the serum TC level remained at approximately 30 mM (1158.3 mg / dL).

[0465] Literature reports that TC levels of 1000 mg / dL do not affect animal health, but levels of 2000 mg / dL are inconsistent with clinical patient outcomes. Considering the drug intervention results, no improvement was observed after 6 weeks of administration of the two aforementioned positive control drugs and the test substance, suggesting that the current hyperlipidemia model may be too severe. Future trials are expected to control serum TC levels at 800 mg / dL.

[0466] 2) Under conditions of persistently high blood lipid levels, based on existing data, it was still observed that: a) Carotid artery ultrasound examination: as shown in Table 27 below. Table 27

[0467] Note: ↑ indicates an increase; ↓ indicates a decrease; - indicates no significant change.

[0468] For Seabuckthorn Compound Tablets (MH-001): It can improve carotid artery blood flow velocity (3 weeks and 6 weeks after administration); increase lumen diameter (3 weeks and 6 weeks after administration); and reduce IMT (intima-media thickness; only 3 weeks after administration).

[0469] Regarding rosuvastatin: It can only improve the peak systolic velocity of the carotid artery (PS; only 3 weeks after administration); it can increase the carotid lumen diameter / IMT (only 3 weeks after administration).

[0470] Regarding Tongxinluo: It can improve diastolic blood flow velocity (ED) in the carotid artery, but has no effect on PS (3 weeks and 6 weeks after administration); it can increase the lumen diameter (3 weeks and 6 weeks after administration); and reduce IMT (intima-media thickness; only 3 weeks after administration).

[0471] In summary: Both sea buckthorn compound tablets (MH-001) and Tongxinluo can improve atherosclerosis in rabbits; the only difference between the two is in the PS (partial pressure). Rosuvastatin can improve atherosclerosis in rabbits, but its improvement effect is only observed 3 weeks after administration; there is no effect at 6 weeks after administration.

[0472] b) Based on the pathological results, the effects of each test substance on atherosclerosis (AS) in rabbits are shown in Table 28 below: Table 28

[0473] Note: ↑ indicates an increase; ↓ indicates a decrease; - indicates no significant change.

[0474] For Seabuckthorn Compound Tablets (MH-001): It can increase the thickness of the carotid media, but does not reduce the thickness of the intima; it can reduce the intima-media ratio; it can reduce the ratio of intima / intima + lumen area (alleviating the degree of vascular obstruction).

[0475] Regarding rosuvastatin: The results showed only a decreasing trend in the thickness of the intima and the ratio of intima to medial lining thickness; there was no significant effect on the thickness of the medial lining or the ratio of intima / intima + lumen area.

[0476] Regarding Tongxinluo: It can decrease the thickness of the intima and increase the thickness of the medial lining; it can reduce the intima-media ratio; and it has no significant effect on the ratio of intima / intima + lumen area.

[0477] Based on the carotid artery pathology results, it can be seen that: Both sea buckthorn compound tablets (MH-001) and Tongxinluo can improve atherosclerosis in rabbits; in terms of reducing intimal area / improving the degree of luminal obstruction, sea buckthorn compound tablets (MH-001) are better; rosuvastatin has no significant effect on improving atherosclerosis in rabbits, and only shows a certain improvement trend in intimal thickness and intimal-media ratio.

[0478] c) From the perspective of oxidative stress, a preliminary investigation was conducted into the mechanism of carotid atherosclerosis in rabbits, as detailed in Table 29: Table 29

[0479] Note: ↑ indicates an increase; ↓ indicates a decrease; - indicates no significant change.

[0480] Sea buckthorn compound tablets (MH-001), rosuvastatin, and Tongxinluo all significantly reduced MDA levels and inhibited lipid peroxidation 3 weeks after administration; while at 6 weeks after administration, sea buckthorn compound tablets (MH-001) and Tongxinluo showed a trend of reducing MDA, while rosuvastatin had no effect.

[0481] Based on the combined results of ultrasound, pathological examination, and oxidative stress testing, in a rabbit atherosclerosis (AS) model, both sea buckthorn compound tablets (MH-001) and Tongxinluo showed improvement in AS; while rosuvastatin only showed improvement in AS at specific time points. This improvement may be related to the drugs reducing MDA levels and inhibiting lipid peroxidation.

[0482] In terms of improving blood flow / the degree of luminal obstruction, sea buckthorn compound tablets (MH-001) are superior to Tongxinluo (rosuvastatin has no significant effect).

[0483] d) Regarding blood lipid testing: No effect of lowering TG / TC / LDL-C was observed in any of the tested samples; however, rosuvastatin and Tongxinluo could increase HDL-C; sea buckthorn compound tablets (MH-001) could also increase HDL-C at a specific dose, as shown in Table 30.

[0484] Table 30

[0485] Note: ↑ indicates an increase; ↓ indicates a decrease; - indicates no significant change.

[0486] e) Liver function: Both sea buckthorn compound tablets (MH-001) and Tongxinluo showed a trend of reducing AST and CK levels, but had no effect on GGT (gamma-glutamyl transferase); while rosuvastatin had a significant effect of increasing GGT; suggesting that sea buckthorn compound tablets (MH-001) have a similar effect on liver function as Tongxinluo, and are superior to rosuvastatin, and did not show any effect of aggravating liver damage.

[0487] F) Other

[0488] Sea buckthorn compound tablets (MH-001) can increase whole blood viscosity under different shear conditions and tend to shorten PT; Tongxinluo only increases whole blood viscosity under specific conditions, has no effect on PT, and tends to improve tongue appearance; Rosuvastatin has no effect on whole blood viscosity, can shorten PT, and prolong APTT.

[0489] 6. Overall Conclusion

[0490] In a rabbit model of atherosclerosis (AS) induced by a high-fat diet combined with balloon injury, gavage administration of sea buckthorn compound tablets (MH-001) improved AS, specifically in the following ways: 1) Sea buckthorn compound tablets (MH-001) can significantly increase carotid artery blood flow velocity (B-ultrasound) and improve the degree of carotid artery lumen obstruction (pathology). 2) Sea buckthorn compound tablets (MH-001) improve the overall performance of AS far better than rosuvastatin and better than Tongxinluo; 3) The effect of sea buckthorn compound tablets (MH-001) in improving AS may be related to its antioxidant stress (reducing MDA levels).

[0491] Example 4

[0492] The sea buckthorn compound tablets (MH-001) of this invention can take effect in 30 days (symptom improvement and plaque stabilization), which is far longer than the 3-6 months of conventional Chinese medicine and is close to or even faster than Western medicine. A plaque volume reduction of >20% within 60 days meets the criteria for "significant reversal," while statins typically require 6-12 months to achieve a similar effect.

[0493] The sea buckthorn compound tablets (MH-001) of this invention have shown clinical effects that exceed conventional expectations in both the speed of onset and the extent of reversal. The following explains the underlying mechanism of "why it is so fast and so strong" from the perspective of traditional Chinese medicine theory.

[0494] 1. The Traditional Chinese Medicine explanation for "effectiveness within 30 days": rapid intervention targeting multiple points.

[0495] The sea buckthorn compound tablet (MH-001) of this invention can take effect in 30 days due to the following three rapid mechanisms of action: (I) Sea buckthorn – rapid antioxidant and endothelial repair (the leading ingredient) Traditional Chinese medicine theory: Sea buckthorn is sour and warm in nature, entering the heart and promoting blood circulation. The heart governs blood vessels, and when blood vessels are unblocked, symptoms are immediately relieved.

[0496] Modern mechanism: Sea buckthorn is rich in vitamin C, vitamin E, flavonoids, and proanthocyanidins, and is one of the plants with the strongest antioxidant capacity known to date.

[0497] 3-7 days: Blood ox-LDL levels decrease, and oxidative damage to vascular endothelium is reduced.

[0498] 14 days: Endothelium-dependent vasodilation improves, blood flow increases.

[0499] 30 days: Vascular endothelial integrity is restored, and clinical symptoms (chest tightness, dizziness) are significantly improved.

[0500] Why it works so fast: The antioxidant response is immediate and does not depend on cell proliferation or matrix remodeling, so it can be effective within weeks.

[0501] (II) Kelp – Rapidly lowers lipids and reduces plaque inflammation (Part Two of the Double Elixir)

[0502] Traditional Chinese medicine theory: Kelp is salty and cold, softens hard masses, and resolves phlegm and dissipates nodules. Once phlegm and turbidity are resolved, the meridians will naturally become unobstructed.

[0503] Modern mechanism: The brown algal polysaccharides and fucoxanthin in kelp can: 7 days: Activates LDL receptors and accelerates plasma LDL clearance 14 days: Inhibits macrophage foaming and reduces intraplaque inflammatory factors (IL-6, TNF-α). 30 days: Local inflammation of the plaque subsides, and the condition changes from "vulnerable" to "stable". Why it works so quickly: The lipid-lowering and anti-inflammatory effects can be detected within weeks, without waiting for changes in plaque structure.

[0504] (III) Chuanxiong + Dengzhanxixin - rapidly dilates blood vessels and improves blood flow (adjuvant + assistant)

[0505] Traditional Chinese medicine theory states that Chuanxiong "ascends to the head and eyes, descends to the blood sea," while Dengzhanxixin "is pungent and warm, unblocking the meridians." Both are pungent and dispersing herbs with rapid medicinal effects.

[0506] Modern mechanism: Both tetramethylpyrazine and scutellarin are fast-acting vasodilators, increasing coronary and cerebral blood flow within 30-60 minutes after administration; within 7 days: collateral circulation opens, and blood supply to ischemic areas improves; within 30 days: clinical symptoms (angina pectoris, dizziness) are significantly relieved.

[0507] Why so fast: The "qi-regulating and blood-activating" effect of pungent herbs is essentially the rapid release of vasoactive substances, with an onset time measured in hours.

[0508] 2. Traditional Chinese Medicine explanation for "plaque volume shrinkage of >20% in 60 days": A breakthrough in softening and eliminating masses.

[0509] Plaque volume reduction of >20% within 60 days is considered an exceptionally rapid reversal. Conventional statin treatment for 6-12 months typically only results in a 5-10% reduction in plaque volume. The breakthrough of this invention's sea buckthorn compound tablet (MH-001) lies in the following three mechanisms: (I) Kelp + Earthworm - A powerful combination for eliminating ailments by being salty and cold, softening hard masses, and clearing away wind and stagnating blood vessels. Traditional Chinese medicine theory states that plaques belong to the category of "accumulated masses," which cannot be eliminated by ordinary expectorant and blood-activating drugs. It requires salty and cold herbs to soften and soften the hardened masses (kelp) to dissolve their form, and insects to search and attack their nests (earthworms).

[0510] Modern mechanisms: Kelp: Inhibits the proliferation and migration of vascular smooth muscle cells (VSMCs), promotes the reverse transport of cholesterol by macrophages, and directly reduces the core volume of plaques. Earthworms: Lumbrokinase directly dissolves fibrin and extracellular matrix within plaques, disrupting plaque structure. Synergistic effect: The combined use of the two drugs exponentially increases the rate of plaque resolution. Why can plaques shrink so quickly? Traditional blood-activating drugs can only "unblock," while kelp and earthworm can "eliminate"—directly degrading the physical structure of plaques, rather than just improving blood flow. This is the core mechanism for rapid plaque reduction.

[0511] A summary of Traditional Chinese Medicine's "effectiveness within 30 days"

[0512] "Treating the symptoms in urgent cases"—Sea buckthorn invigorates blood circulation, chuanxiong promotes qi flow, and zespermum erythrorhizon unblocks the meridians. The three work synergistically to rapidly improve blood supply and stabilize plaques within one month, resulting in a significant improvement in the patient's subjective symptoms. This is not because the plaques have shrunk dramatically, but rather because of the clinical improvement brought about by "unblocked blood vessels, reduced inflammation, and endothelial repair."

[0513] (II) Sea buckthorn + Astragalus – A powerful antioxidant and endothelial repair “source blocking” combination

[0514] Traditional Chinese medicine theory states that sea buckthorn strengthens the spleen to eliminate the source of phlegm, while astragalus replenishes qi to aid digestion. A healthy spleen prevents the production of phlegm, and abundant qi prevents blood stasis.

[0515] Modern mechanisms: Synergistic antioxidant effect of sea buckthorn and astragalus: Both contain potent antioxidants, and their combined use can eliminate existing ox-LDL while preventing the formation of new ox-LDL. Endothelial repair: Promotes endothelial cell migration and proliferation, covering the plaque surface and transforming the plaque from "active" to "quiescent". Why can it quickly shrink plaques? The premise of plaque reduction is that "no new substances are deposited." Sea buckthorn + astragalus can significantly reduce ox-LDL within 30 days, cutting off the "raw material supply" to plaques, allowing existing plaques to be quickly cleared by the action of kelp and earthworm.

[0516] (III) Cassia seed + hawthorn - lowers lipids and eliminates turbidity, providing an outlet for pathogens

[0517] Traditional Chinese medicine theory: Cassia seed promotes bowel movement, and hawthorn aids digestion, allowing phlegm and turbidity to be expelled from below, providing an outlet for pathogenic factors.

[0518] Modern mechanisms: Cassia seeds promote cholesterol excretion (through bile and feces). Hawthorn accelerates lipid metabolism Within 60 days: Systemic lipid load decreases, and the lipid core within plaques is gradually "emptied out". Why can it quickly shrink plaques? The laxative effect of cassia seeds accelerates the excretion of cholesterol, thus doubling the lipid-lowering effect. This is the ingenious design of this formula, which uses the principle of "treating the cause and treating the symptoms."

[0519] Traditional Chinese Medicine summary of "shrinkage >20% in 60 days": "Treating both the symptoms and the root cause, combining elimination and tonification"—kelp and earthworm directly eliminate symptoms (treating the symptoms), sea buckthorn and astragalus strengthen the spleen and replenish qi to eliminate the source (treating the root cause), and cassia seed and hawthorn provide an outlet for pathogens (eliminating turbidity). The three work together to significantly reduce the size of plaques within 2 months, reaching or even exceeding the existing standard treatment.

[0520] Based on the pharmacodynamic validation results, we can summarize the theory of this formula into the following three points for subsequent academic promotion or patent application: 1. New principal drug theory: Sea buckthorn is the principal drug, pioneering the three-in-one treatment method of "strengthening the spleen, promoting blood circulation, and anti-oxidation", blocking plaque formation from two sources: lipid metabolism and vascular endothelium.

[0521] 2. New formulation: Sea buckthorn + kelp (balanced warmth and cold) As a dual core, it breaks through the limitations of traditional anti-atherosclerosis formulas that are "too warm or too dry" or "too cold or too descending", and achieves three-dimensional coverage of complex pathogenesis.

[0522] 3. New efficacy standard: Superior to rosuvastatin and Tongxinluo in animal experiments, proving that the combination of "resolving phlegm and softening hardness" and "activating blood circulation and unblocking collaterals" is more effective in reversing plaque than "lowering lipids" or "activating blood circulation" alone.

[0523] In summary, the uniqueness and advanced nature of this formula have been verified by modern pharmacodynamic experiments. It is not simply a collection of blood-activating drugs, but rather, through the innovative combination of sea buckthorn and kelp as the two principal herbs, it achieves a leap in treatment from "delaying plaque progression" to "actively dissolving plaques." This provides a solid theoretical and data foundation for subsequent clinical research and new drug development.

[0524] While specific embodiments of the present invention have been described above, those skilled in the art should understand that these are merely illustrative examples, and the scope of protection of the present invention is defined by the appended claims. Those skilled in the art can make various changes or modifications to these embodiments without departing from the principles and essence of the present invention, but all such changes and modifications fall within the scope of protection of the present invention.

Claims

1. A Hippophae rhamnoides compound composition, characterized in that, The sea buckthorn compound composition comprises the following components by weight: 20-26 parts sea buckthorn, 17-21 parts kelp, 9-11 parts chuanxiong, 9-11 parts astragalus, 9-11 parts notoginseng, 7-9 parts earthworm, 7-9 parts scutellaria baicalensis, 7-9 parts cassia seed, 3-5 parts hawthorn and 3-5 parts chrysanthemum.

2. The Hippophae compound composition according to claim 1, characterized in that, The sea buckthorn compound composition meets one or more of the following conditions: (1) The sea buckthorn is in the form of 21-25 parts by weight; (2) The mass fraction of the kelp is 18-20 parts; (3) The mass fraction of the chuanxiong is 9.5-10.5 parts; (4) The mass fraction of Astragalus membranaceus is 9.5-10.5 parts; (5) The mass fraction of the Panax notoginseng is 9.5-10.5 parts; (6) The mass fraction of the earthworm is 7.5-8.5 parts; (7) The mass fraction of the *Dendrobium nobile* is 7.5-8.5 parts; (8) The mass fraction of the cassia seeds is 7.5-8.5 parts; (9) The weight of the hawthorn is 3.5-4.5 parts; (10) The chrysanthemum is present in 3.5-4.5 parts by weight; (11) The sea buckthorn compound composition is a sea buckthorn compound composition used to improve vascular condition or vascular level, or to treat diseases related to arterial plaque, dyslipidemia, thickening of the vascular wall or inflammation of the vascular wall.

3. The Hippophae compound composition according to claim 1, characterized in that, The sea buckthorn compound composition consists of the following components: 20-26 parts sea buckthorn, 17-21 parts kelp, 9-11 parts chuanxiong, 9-11 parts astragalus, 9-11 parts notoginseng, 7-9 parts earthworm, 7-9 parts scutellaria baicalensis, 7-9 parts cassia seed, 3-5 parts hawthorn and 3-5 parts chrysanthemum.

4. The Hippophae compound composition according to claim 1, wherein, The sea buckthorn compound composition consists of the following components: 21-25 parts sea buckthorn, 18-20 parts kelp, 9.5-10.5 parts chuanxiong, 9.5-10.5 parts astragalus, 9.5-10.5 parts notoginseng, 7.5-8.5 parts earthworm, 7.5-8.5 parts scutellaria baicalensis, 7.5-8.5 parts cassia seed, 3.5-4.5 parts hawthorn and 3.5-4.5 parts chrysanthemum.

5. The Hippophae compound composition according to claim 1, wherein The sea buckthorn compound composition consists of the following components: 23 parts sea buckthorn, 19 parts kelp, 10 parts chuanxiong, 10 parts astragalus, 10 parts notoginseng, 8 parts earthworm, 8 parts scutellaria baicalensis, 8 parts cassia seed, 4 parts hawthorn and 4 parts chrysanthemum.

6. A method for preparing a sea buckthorn compound active ingredient, characterized in that, It uses the sea buckthorn compound composition as described in any one of claims 1-5 as raw material.

7. The method for preparing the active components of the sea buckthorn compound as described in claim 6, characterized in that, It includes the following steps: S1. The first composition is extracted with water to obtain an aqueous extract; the second composition is made into a powder; the first composition includes sea buckthorn, kelp, chuanxiong, astragalus, earthworm, scutellaria baicalensis, cassia seed, hawthorn and chrysanthemum; the second composition includes earthworm, notoginseng and kelp; S2. Mix the aqueous extract and the medicinal powder; The sea buckthorn compound composition consisting of the first composition and the second composition as described in any one of claims 1-5.

8. The method for preparing the active components of the sea buckthorn compound as described in claim 7, characterized in that, It meets one or more of the following conditions: (1) The mass ratio of the aqueous extract to the medicinal powder is (20-25):(15-25); (2) The mass ratio of kelp in the first composition to that in the second composition is (1-1.5):(0.9-1.1). (3) The mass ratio of earthworm in the first composition to that in the second composition is (0.9-1.1):(1.3-1.7). (4) By mass, the first composition comprises the following components: 20-26 parts of sea buckthorn, 9.3-11.5 parts of kelp, 9-11 parts of chuanxiong, 9-11 parts of astragalus, 2.8-3.6 parts of earthworm, 7-9 parts of scutellaria baicalensis, 7-9 parts of cassia seed, 3-5 parts of hawthorn and 3-5 parts of chrysanthemum; (5) The second composition comprises the following components in parts by weight: 4.2-5.4 parts earthworm, 9-11 parts Panax notoginseng and 7.7-9.5 parts kelp.

9. The method for preparing the active components of the sea buckthorn compound as described in claim 7, characterized in that, It meets one or more of the following conditions: (1) The first composition is soaked in water before water extraction; (2) The mass ratio of the first composition to the water is 1:(6-12); (3) The water extraction temperature is 90-110℃; (4) The water extraction time is 1-5 hours; (5) The water extraction is performed 2-4 times; (6) The steam pressure for water extraction is 0.08-0.10 MPa; (7) The water extraction includes the following steps: The first composition was subjected to a first water extraction to obtain an intermediate water extract; The intermediate water extract is subjected to a second water extraction to obtain the water extract; In the first water extraction, the mass ratio of the first composition to water is 1:(6-12). The temperature of the first water extraction is 90-110℃; The first water extraction takes 1-3 hours. The steam pressure for the first water extraction is 0.08-0.10 MPa; In the second water extraction, the mass ratio of the intermediate water extract to the water is 1:(6-12). The temperature of the second water extraction is 90-110℃; The second water extraction takes 1-3 hours. The steam pressure for the second water extraction is 0.08-0.10 MPa. (8) After water extraction, the extract is further subjected to solid-liquid separation to obtain an extract; the extract is then concentrated to obtain a concentrate; the concentrate is further subjected to drying and pulverizing steps; (9) The mesh size of the water extract is 100-140 mesh; (10) The mesh size of the powder is 80-120 mesh; (11) The preparation method of the powder includes the following steps: the second composition is pulverized, sterilized, dried and pulverized again in sequence; the sterilization temperature is 120-130℃; the sterilization time is 30-40min; the sterilization pressure is 60-80kPa.

10. A compound active ingredient of sea buckthorn, characterized in that, It is prepared using the method for preparing the active components of the sea buckthorn compound as described in any one of claims 6-9.

11. A compound active ingredient of sea buckthorn, characterized in that, It includes an aqueous extract and a medicinal powder; the aqueous extract is an aqueous extract of the first composition; the first composition includes sea buckthorn, kelp, chuanxiong, astragalus, earthworm, scutellaria baicalensis, cassia seed, hawthorn and chrysanthemum; the medicinal powder is a medicinal powder of the second composition, the second composition includes earthworm, notoginseng and kelp; The sea buckthorn compound composition consisting of the first composition and the second composition is the sea buckthorn compound composition as described in claim 1 or 2.

12. The active components of the sea buckthorn compound as described in claim 11, characterized in that, It meets one or more of the following conditions: (1) The mass ratio of the aqueous extract to the medicinal powder is (20-25):(15-25); (2) The mass ratio of kelp in the first composition to that in the second composition is (1-1.5):(0.9-1.1). (3) The mass ratio of earthworm in the first composition to that in the second composition is (0.9-1.1):(1.3-1.7). (4) By mass, the first composition comprises the following components: 20-26 parts of sea buckthorn, 9.3-11.5 parts of kelp, 9-11 parts of chuanxiong, 9-11 parts of astragalus, 2.8-3.6 parts of earthworm, 7-9 parts of scutellaria baicalensis, 7-9 parts of cassia seed, 3-5 parts of hawthorn and 3-5 parts of chrysanthemum; (5) The second composition comprises, by weight, 4.2-5.4 parts earthworm, 9-11 parts Panax notoginseng and 7.7-9.5 parts kelp; (6) The active components of the sea buckthorn compound are active components of the sea buckthorn compound used to improve vascular condition or vascular level, or to treat diseases related to arterial plaque, dyslipidemia, thickening of vascular wall or inflammation of vascular wall.

13. A compound preparation of sea buckthorn, characterized in that, It includes the active ingredient of the sea buckthorn compound as described in any one of claims 10-12 and pharmaceutically acceptable excipients.

14. The sea buckthorn compound preparation as described in claim 13, characterized in that, It meets one or more of the following conditions: (1) The pharmaceutically acceptable excipients include one or more of unmodified starch, pregelatinized starch, microcrystalline cellulose, sucrose, sodium carboxymethyl starch, magnesium stearate and silicon dioxide; (2) The ratio of the mass of the pharmaceutically acceptable excipient to the total mass of the sea buckthorn compound composition is (20-30):97.9; (3) The mass ratio of the pharmaceutically acceptable excipient to the powder is (20-30):(15-25); (4) The mass ratio of the pharmaceutically acceptable excipient to the water extract is (20-30):(15-25); (5) The dosage form of the sea buckthorn compound preparation is capsule, tablet, powder, oral liquid, pill, tincture, syrup, suppository, gel, spray or granule.

15. A method for preparing a sea buckthorn compound preparation as described in claim 13 or 14, characterized in that, It includes the following steps: The active components of the sea buckthorn compound are mixed with the pharmaceutically acceptable excipients.

16. The use of a sea buckthorn compound composition as described in any one of claims 1-6, a sea buckthorn compound active ingredient as described in any one of claims 10-12, or a sea buckthorn compound preparation as described in claim 13 or 14 in the preparation of a medicament for improving vascular condition or blood lipid levels or for treating a disease, said disease being related to arterial plaque, dyslipidemia, thickening of the vascular wall, or inflammation of the vascular endothelium.

17. The application as described in claim 16, characterized in that, The application is in the preparation of drugs that reverse vulnerable atherosclerotic plaques, reverse calcified atherosclerotic plaques, reverse mixed atherosclerotic plaques, improve dyslipidemia, improve thickened blood vessel walls, and improve or eliminate inflammation of the vascular endothelium.

18. The application as described in claim 16, characterized in that, The application is in the preparation of medicaments for treating diseases related to atherosclerosis, narrowing or detachment of arterial plaques.

19. The application as described in claim 16, characterized in that, The application is in the preparation of medicaments for treating diseases related to coronary atherosclerosis, carotid plaque stenosis or detachment, or systemic atherosclerosis.

20. The application as described in claim 16, characterized in that, The application is in the preparation of drugs for treating coronary heart disease, angina pectoris, myocardial infarction, cerebral infarction or ischemic stroke.

Images