Traditional Chinese medicine preparation for treating or improving cognitive impairment

Abstract

The invention provides a traditional Chinese medicine preparation for treating or improving cognitive impairment, and particularly relates to the technical field of traditional Chinese medicine pharmacy. The traditional Chinese medicine preparation is prepared from the following raw materials: rhizoma atractylodis, radix pseudostellariae, flatstem milkvetch seed, oviductus ranae, trogopterus dung, cynanchum glaucescens, amber, Japanese ardisia herb, Chinese honey locust, calculus bovis factitius, armeniaca mume, trichosanthes kirilowii maxim and maltose. In the traditional Chinese medicine preparation, oviductus ranae and calculus bovis factitius are used as monarch drugs, flatstem milkvetch seeds, Chinese honey locust, rhizoma atractylodis, trogopterus dung and amber are used as ministerial drugs, radix pseudostellariae, cynanchum glaucescens, Japanese ardisia herb, trichosanthes kirilowii maxim, armeniaca mume and maltose are used as adjuvant drugs, and the whole formula has the effects of tonifying kidney and filling marrow to treat root causes, eliminating phlegm and inducing resuscitation, promoting blood circulation to remove blood stasis, clearing heat and reducing phlegm to treat symptoms, tonifying spleen and replenishing qi, and soothing liver and regulating qi; all the components are used together, so that the effects of replenishing marrow, nourishing brain, inducing resuscitation, promoting intelligence and improving cognition are achieved. The traditional Chinese medicine preparation is expected to be further developed and applied as a new medicine for treating or improving cognitive impairment.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine pharmaceutical technology, specifically to a traditional Chinese medicine preparation for treating or improving cognitive impairment. Background Technology

[0002] Alzheimer's disease (AD), a chronic progressive neurodegenerative disease, is characterized by its insidious onset, with its preclinical phase lasting for decades during which patients typically do not exhibit obvious neurological symptoms. This long, asymptomatic preclinical phase means that the pathophysiological processes of AD have already begun to change and progress silently before clinical symptoms appear. Mild cognitive impairment (MCI), as a transitional state between normal aging and dementia, manifests as memory impairment and / or other cognitive dysfunctions such as episodic memory, executive function, and attention. It is considered a window for early intervention in AD; without timely intervention, it will impose a huge economic burden on families and society. In current clinical treatment, improving cognitive function mainly relies on the use of cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. However, these drugs can only temporarily relieve symptoms and cannot effectively stop the progression of the disease, and long-term use may cause various side effects. Traditional Chinese medicine has a long history of understanding cognitive impairment. Due to the characteristics of traditional Chinese medicine, such as multiple targets and low toxicity, it has unique advantages in improving clinical symptoms of cognitive impairment and delaying disease progression. Summary of the Invention

[0003] (a) Technical problems to be solved

[0004] In view of the shortcomings of the prior art, the present invention provides a traditional Chinese medicine preparation for treating or improving cognitive impairment.

[0005] (II) Technical Solution

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] In a first aspect, the present invention provides a traditional Chinese medicine preparation for treating or improving cognitive impairment, the preparation being made from the following traditional Chinese medicinal materials in parts by weight: 10-40 parts of Atractylodes lancea, 10-40 parts of Codonopsis pilosula, 10-40 parts of Astragalus complanatus, 10-40 parts of toad oil, 10-40 parts of Trogopterus xanthipes, 10-40 parts of Cynanchum paniculatum, 10-40 parts of amber, 10-40 parts of Dioscorea opposita, 10-40 parts of Gleditsia sinensis, 10-40 parts of artificial bezoar, 10-40 parts of Prunus mume, 10-40 parts of Trichosanthes kirilowii, and 10-40 parts of maltose.

[0008] Furthermore, the traditional Chinese medicine preparation is made from the following traditional Chinese medicinal materials in parts by weight: 20-40 parts of Atractylodes lancea, 15-30 parts of Codonopsis pilosula, 20-40 parts of Astragalus complanatus, 20-40 parts of toad oil, 20-40 parts of Trogopterus xanthipes, 15-30 parts of Cynanchum paniculatum, 20-40 parts of amber, 15-30 parts of Dioscorea opposita, 20-40 parts of Gleditsia sinensis, 20-40 parts of artificial bezoar, 15-30 parts of Prunus mume, 15-30 parts of Trichosanthes kirilowii, and 15-30 parts of maltose.

[0009] Furthermore, the traditional Chinese medicine preparation is made from the following traditional Chinese medicinal materials in parts by weight: 28 parts of Atractylodes lancea, 20 parts of Codonopsis pilosula, 30 parts of Astragalus complanatus, 36 parts of toad oil, 24 parts of Trogopterus xanthipes, 18 parts of Cynanchum paniculatum, 26 parts of amber, 20 parts of Dioscorea opposita, 28 parts of Gleditsia sinensis, 32 parts of artificial bezoar, 22 parts of Prunus mume, 24 parts of Trichosanthes kirilowii, and 16 parts of maltose.

[0010] Furthermore, the traditional Chinese medicine preparation uses the above-mentioned proportions of Chinese medicinal materials as raw materials, supplemented with pharmaceutically acceptable excipients, and is prepared according to conventional preparation methods to produce an oral dosage form for treating or improving cognitive impairment. The dosage form includes any one of decoction, oral liquid, pill, powder, granule, capsule, tablet, and ointment.

[0011] Secondly, the present invention provides a method for preparing a traditional Chinese medicine decoction for treating or improving cognitive impairment, wherein the oral liquid is prepared according to the following steps:

[0012] (1) Weigh out each Chinese medicinal material according to the following weight parts: Atractylodes lancea 10-40 parts, Codonopsis pilosula 10-40 parts, Astragalus complanatus 10-40 parts, toad oil 10-40 parts, Trogopterus xanthipes 10-40 parts, Cynanchum paniculatum 10-40 parts, amber 10-40 parts, Dioscorea opposita 10-40 parts, Gleditsia sinensis 10-40 parts, artificial bezoar 10-40 parts, green plum blossom 10-40 parts, Trichosanthes kirilowii 10-40 parts, maltose 10-40 parts;

[0013] (2) Pretreatment: Remove impurities and wash Atractylodes lancea, Codonopsis pilosula, Astragalus complanatus, Trogopterus xanthipes, Cynanchum paniculatum, Dioscorea opposita, Gleditsia sinensis, Trichosanthes kirilowii, and Prunus mume; cut Gleditsia sinensis into pieces and Trichosanthes kirilowii into chunks; soak toad oil in warm water at 40-50℃ for more than 30 minutes until fully expanded, wash away impurities, and dry; wash amber and artificial bezoar, remove impurities, dry, and grind into very fine powder;

[0014] (3) Place the pretreated toad oil, Atractylodes lancea, Codonopsis pilosula, Astragalus complanatus, Trogopterus xanthipes, Cynanchum paniculatum, Dioscorea opposita, Gleditsia sinensis, Trichosanthes kirilowii, and Prunus mume into an extraction tank, add 10-14 times the amount of purified water, and soak for 1-1.5 hours; then heat to boiling and maintain a gentle boil for more than 2 hours, filter, retain the first decoction, add 8-12 times the amount of purified water to the residue, heat to boiling and maintain a gentle boil for more than 1.5 hours, filter, retain the second decoction, add 8-10 times the amount of purified water to the residue, heat to boiling and maintain a gentle boil for more than 1.5 hours, filter, retain the third decoction; combine the three decoctions.

[0015] (4) The decoction is concentrated under reduced pressure to a clear extract with a relative concentration of 2.0 to 2.3; then 95% ethanol is added for precipitation to make the alcohol content of the system reach 60% to 65%, and after stirring, it is refrigerated and allowed to stand for more than 24 hours; then the supernatant is taken off, and the system ethanol is recovered by reduced pressure distillation until there is no alcohol taste, to obtain the concentrated liquid;

[0016] (5) Then the maltose is heated and melted with purified water, and then the above concentrated solution is added. Then artificial bezoar and amber powder are added and stirred evenly to obtain a refined concentrated solution.

[0017] (6) The purified concentrate prepared in step (5) is used as the active ingredient. Pharmaceutically acceptable excipients are added and the traditional Chinese medicine oral liquid dosage form is prepared according to conventional pharmaceutical techniques.

[0018] All the medicinal materials in the traditional Chinese medicine preparation of this invention are processed according to traditional pharmaceutical techniques or the requirements of the Chinese Pharmacopoeia. The relevant descriptions of each medicinal material in the preparation are as follows:

[0019] Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz., belonging to the genus Atractylodes of the Asteraceae family, is a dried rhizome. It has the effects of drying dampness and strengthening the spleen, dispelling wind and cold, and improving eyesight. It is mainly used to treat dampness obstructing the middle jiao, abdominal distension, diarrhea, edema, beriberi, rheumatic pain, common cold due to wind-cold, night blindness, and blurred vision.

[0020] Codonopsis pilosula: The dried tuberous root of Codonopsis pilosula, a plant of the Caryophyllaceae family. It is neutral in nature, sweet and slightly bitter in taste, and enters the spleen and lung meridians. It is a commonly used qi-tonifying herb that invigorates qi, strengthens the spleen, promotes body fluid production, and moistens the lungs. It is suitable for symptoms such as spleen deficiency and fatigue, loss of appetite, weakness after illness, qi and yin deficiency, spontaneous sweating and thirst, and dry cough due to lung dryness.

[0021] Astragalus complanatus R.Br., a plant belonging to the genus Astragalus in the legume family, is a dried, mature seed. It has the effects of tonifying the kidneys and strengthening essence, reducing urination, nourishing the liver, and improving eyesight. It is mainly used to treat kidney deficiency with lower back pain, seminal emission, premature ejaculation, enuresis, frequent urination, leukorrhea, dizziness, and blurred vision.

[0022] Toad oil: A traditional Chinese medicine made from the dried oviduct of the female Chinese forest frog (Rana chinensis). It is sweet, salty and neutral in nature, and enters the lung and kidney meridians. It has the effects of tonifying the kidney and replenishing essence, nourishing yin and moistening the lungs. It is suitable for symptoms such as weakness after illness, palpitations, insomnia, and hemoptysis.

[0023] Wulingzhi: It is the dried feces of the flying squirrel (Pterygodon fasciatus), a member of the flying squirrel family. It is bitter, sweet, and warm in nature, and enters the liver meridian. It has the effects of promoting blood circulation and removing blood stasis, and stopping bleeding when charred. Clinically, it is often used for gynecological diseases, pain due to blood stasis, and external bleeding.

[0024] Baiqian: It is the dried rhizome and root of Baiqian or Baiqian daphne, plants of the Asclepiadaceae family. It is slightly warm in nature, pungent and bitter in taste, and enters the lung meridian. It has the effects of lowering qi and resolving phlegm, relieving cough and asthma. It is mainly used to treat symptoms such as lung qi stagnation, excessive phlegm and cough.

[0025] Amber: A hydrocarbon compound formed from the resin of ancient pine trees that has been buried underground for a long time; it is sweet and neutral in nature, and enters the heart, liver and bladder meridians. It has the effects of calming the mind and relieving fright, promoting blood circulation and removing blood stasis, and promoting urination. It is often used for palpitations, insomnia, infantile convulsions, epilepsy, dysmenorrhea, amenorrhea and difficulty urinating.

[0026] Ardisia japonica (Thunb.) Blume., a plant in the Myrsinaceae family, is a dried whole herb. It is neutral in nature, slightly bitter and pungent in taste, and has the effects of resolving phlegm and relieving cough, clearing damp-heat, and promoting blood circulation. It is used to treat acute and chronic cough, wheezing with excessive phlegm, damp-heat jaundice, amenorrhea due to blood stasis, rheumatic pain, and traumatic injuries.

[0027] Soapberry: A deciduous tree or small tree belonging to the genus Soapberry in the legume family. Its Chinese scientific name is soapberry, also known as soap pod. It has a pungent, salty and warm nature and enters the lung, liver, stomach and large intestine meridians. It has the effects of relieving phlegm and cough, opening the orifices and clearing blockages, killing parasites and dispersing nodules. It is mainly used to treat symptoms such as cough with phlegm and wheezing, and stroke with delirium.

[0028] Artificial bezoar: An artificially prepared bezoar substitute, made from bovine bile powder, cholic acid, deoxycholic acid from pigs, taurine, bilirubin, cholesterol, trace elements, etc., with effects similar to natural bezoar; it has the effects of clearing heat and detoxifying, resolving phlegm and calming convulsions. It is often used to treat symptoms such as delirium due to phlegm-heat, coma and aphasia, infantile convulsions, sore throat, mouth ulcers, carbuncles and boils.

[0029] Green calyx plum: The flower of *Prunus mume* Sieb. et Zucc. var. *viridicalyx Makino*, a plant in the genus *Prunus* of the Rosaceae family. It has a bitter and slightly sweet taste, and is neutral in nature. It has the effects of calming the liver and stomach, and is mainly used to treat chest and rib pain, stomach pain, indigestion, and neurasthenia.

[0030] Trichosanthes kirilowii Maxim. and Trichosanthes rosthornii Harms, both belonging to the genus Trichosanthes in the Cucurbitaceae family, are dried, ripe fruits. They possess the effects of clearing heat and resolving phlegm, relieving chest congestion and dissipating nodules, and moistening dryness and lubricating the intestines. They are primarily used to treat coughs due to lung heat, thick yellow phlegm, chest pain, chest tightness and fullness, mastitis, lung abscess, intestinal abscess, and constipation.

[0031] Maltose: It is made from grains such as corn, barley, wheat, millet or maize through fermentation and saccharification; it is sweet and warm in nature, and enters the spleen, stomach and lung meridians. Clinically, it is mainly used to tonify the spleen and replenish qi, relieve pain, moisten the lungs and stop cough, and treat spleen and stomach qi deficiency, middle jiao deficiency and cold, lung deficiency and chronic cough, shortness of breath and wheezing.

[0032] Traditional Chinese medicine categorizes cognitive impairment as "dementia, forgetfulness, idiocy, and amnesia," with its core pathogenesis being deficiency of kidney essence and insufficient replenishment of the marrow, and the manifestations being the mutual binding of phlegm and blood stasis, and phlegm-heat obstructing the sensory orifices, accompanied by spleen and stomach qi deficiency and qi stagnation. This invention, based on the principles of TCM syndrome differentiation and treatment, proposes a Chinese herbal preparation for treating or improving cognitive impairment, made from Atractylodes lancea, Codonopsis pilosula, Astragalus complanatus, toad oil, Trogopterus xanthipes, Cynanchum paniculatum, amber, Lysimachia christinae, Gleditsia sinensis, artificial bezoar, Prunus mume, Trichosanthes kirilowii, and maltose. In this preparation, toad oil and artificial bezoar are the principal ingredients. Toad oil excels at tonifying the kidney and replenishing essence, nourishing yin and replenishing marrow, directly replenishing congenital kidney essence and enriching the brain marrow; artificial bezoar excels at clearing heat and detoxifying, resolving phlegm and opening the orifices, targeting the manifestations of phlegm-heat and turbid toxins obstructing the sensory orifices, such as delirium, forgetfulness, and irritability. The two ingredients, one tonifying and the other clearing, treat both the root cause and the symptoms, working together to tonify deficiency and purge excess. Astragalus complanatus warms and tonifies the liver and kidneys, strengthens essence and reduces urination, and helps toad oil enhance its kidney-tonifying and marrow-replenishing effects; Gleditsia sinensis is effective in clearing phlegm, opening the orifices, dispersing nodules and unblocking stagnation, and helps artificial bezoar clear phlegm, refresh the mind, and unblock the obstructed brain orifices; Atractylodes lancea dries dampness and strengthens the spleen, aromatically transforms turbidity, strengthens the spleen and stomach to cut off the source of phlegm and turbidity, and dries dampness and transforms turbidity to clear the brain orifices from pathogenic factors; Trogopterus xanthipes invigorates blood, removes blood stasis, unblocks collaterals and relieves pain, while amber invigorates blood, disperses blood stasis, calms the mind and unblocks the brain collaterals. The two combined remove the obstruction of the brain collaterals, so that blood stasis is removed, the brain collaterals are unblocked, and the pathogenic factors of phlegm and blood stasis are resolved, assisting the principal drug in removing blood stasis, opening the orifices, calming the mind and stabilizing the will; the five herbs together serve as assistant drugs, supporting the body's resistance and eliminating pathogenic factors, and assisting the principal drug in exerting the effect of treating both the root cause and the symptoms in many ways. In addition, the formula is supplemented with Codonopsis pilosula, Cynanchum paniculatum, Dioscorea opposita, Trichosanthes kirilowii, Prunus mume, and maltose as adjuvant herbs. Codonopsis pilosula invigorates qi and strengthens the spleen, nourishes yin and generates fluids. Together with Atractylodes lancea, it strengthens the spleen and stomach, promotes the flow of qi and blood to nourish the brain and marrow, and is nourishing without causing dryness, while also taking care of qi and yin. Cynanchum paniculatum lowers qi and resolves phlegm, Dioscorea opposita clears heat, resolves phlegm, invigorates blood and removes blood stasis, and Trichosanthes kirilowii clears heat, resolves phlegm, regulates qi and relieves chest tightness. The three herbs work together to enhance the formula's ability to remove phlegm and turbidity and clear away phlegm and heat. Prunus mume soothes the liver, regulates qi, and harmonizes the middle jiao, thus regulating the qi mechanism of the whole body. Soothing the liver helps the qi mechanism to flow smoothly. When qi flows, blood flows, which in turn facilitates the dissipation of phlegm and turbidity. Maltose invigorates the middle jiao and benefits qi, relieves spasms and protects the stomach, and harmonizes the other herbs, so that the whole formula attacks pathogens without harming the body's vital energy, and nourishes without being greasy. The combination of herbs, including the principal, assistant, and adjuvant herbs, is well-balanced, with each herb synergistically enhancing the others. Together, they work to tonify the kidneys and replenish marrow, open the orifices and refresh the mind, resolve phlegm and remove blood stasis, clear heat and resolve phlegm, and strengthen the spleen and regulate qi. This formula has enormous potential for treating or improving cognitive impairment.

[0033] Based on the aforementioned traditional Chinese medicine formulation, this invention uses scopolamine-induced learning and memory impairment in mice as a model to explore and verify the improvement of learning and memory abilities in mice with cognitive impairment by the traditional Chinese medicine preparation of this invention. Experimental results show that the traditional Chinese medicine preparation of this invention can significantly improve the learning and memory abilities of mice with cognitive impairment, mainly by significantly shortening the escape latency and spatial exploration latency, significantly increasing the number of platform crossings and the time spent in the target quadrant, significantly reducing the number of errors, and significantly inhibiting AChE activity in the hippocampus and cortex of the brain. The traditional Chinese medicine preparation of this invention has a significant therapeutic effect on improving or treating cognitive impairment, and its therapeutic effect is comparable to donepezil. In summary, the traditional Chinese medicine preparation of this invention shows promise for further development and application as a new drug for treating or improving cognitive impairment. Attached Figure Description

[0034] Figure 1 This is a schematic diagram of a thermal stimulation combined with a Y-maze experimental setup.

[0035] Figure 2 The results are as follows: A: Escape latency of mice in each group during the 5-day course of the orientation navigation experiment; B: Latency of mice in each group during the spatial exploration experiment; C: Number of times mice in each group crossed platforms during the spatial exploration experiment; D: Time spent in the target quadrant by mice in each group during the spatial exploration experiment; E: Number of learning attempts; F: Number of errors; where ns, P>0.05; compared with the control group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0036] Figure 3 The results of AChE activity assays in the hippocampus (A) and cortex (B) of mouse brain tissue in each group are shown; among them, compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01. Detailed Implementation

[0037] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0038] Example 1

[0039] A traditional Chinese medicine preparation for treating or improving cognitive impairment, the preparation being made from the following traditional Chinese medicinal materials in parts by weight: 12 parts Atractylodes lancea, 12 parts Codonopsis pilosula, 14 parts Astragalus complanatus, 15 parts toad oil, 12 parts Trogopterus xanthipes, 10 parts Cynanchum paniculatum, 10 parts amber, 10 parts Dioscorea opposita, 12 parts Gleditsia sinensis, 15 parts artificial bezoar, 10 parts Prunus mume, 10 parts Trichosanthes kirilowii, and 10 parts maltose.

[0040] The traditional Chinese medicine preparation uses the above-mentioned proportions of Chinese medicinal materials as raw materials, supplemented with pharmaceutically acceptable excipients, and is prepared according to conventional preparation methods to produce an oral dosage form for the treatment or improvement of cognitive impairment. The dosage form includes any one of the following: decoction, oral liquid, pill, powder, granule, capsule, tablet, and ointment.

[0041] The above-mentioned traditional Chinese medicine preparations for treating or improving cognitive impairment can be prepared according to the following steps:

[0042] (1) Weigh each Chinese medicinal material according to the above weight proportions;

[0043] (2) Pretreatment: Remove impurities and wash Atractylodes lancea, Codonopsis pilosula, Astragalus complanatus, Trogopterus xanthipes, Cynanchum paniculatum, Dioscorea opposita, Gleditsia sinensis, Trichosanthes kirilowii, and Prunus mume; cut Gleditsia sinensis into pieces and Trichosanthes kirilowii into chunks; soak toad oil in warm water at 40-50℃ for more than 30 minutes until fully expanded, wash away impurities, and dry; wash amber and artificial bezoar, remove impurities, dry, and grind into very fine powder;

[0044] (3) Place the pretreated toad oil, Atractylodes lancea, Codonopsis pilosula, Astragalus complanatus, Trogopterus xanthipes, Cynanchum paniculatum, Dioscorea opposita, Gleditsia sinensis, Trichosanthes kirilowii, and Prunus mume into an extraction tank, add 10-14 times the amount of purified water, and soak for 1-1.5 hours; then heat to boiling and maintain a gentle boil for more than 2 hours, filter, retain the first decoction, add 8-12 times the amount of purified water to the residue, heat to boiling and maintain a gentle boil for more than 1.5 hours, filter, retain the second decoction, add 8-10 times the amount of purified water to the residue, heat to boiling and maintain a gentle boil for more than 1.5 hours, filter, retain the third decoction; combine the three decoctions.

[0045] (4) The decoction is concentrated under reduced pressure to a clear extract with a relative concentration of 2.0 to 2.3; then 95% ethanol is added for precipitation to make the alcohol content of the system reach 60% to 65%, and after stirring, it is refrigerated and allowed to stand for more than 24 hours; then the supernatant is taken off, and the system ethanol is recovered by reduced pressure distillation until there is no alcohol taste, to obtain the concentrated liquid;

[0046] (5) Then the maltose is heated and melted with purified water, and then the above concentrated solution is added. Then artificial bezoar and amber powder are added and stirred evenly to obtain a refined concentrated solution.

[0047] (6) The purified concentrate prepared in step (5) is used as the active ingredient. Pharmaceutically acceptable excipients are added and the traditional Chinese medicine oral liquid dosage form is prepared according to conventional pharmaceutical techniques.

[0048] Example 2

[0049] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following parts by weight of traditional Chinese medicinal materials: 30 parts of Atractylodes lancea, 32 parts of Codonopsis pilosula, 30 parts of Astragalus complanatus, 38 parts of toad oil, 30 parts of Trogopterus xanthipes, 28 parts of Cynanchum paniculatum, 30 parts of amber, 32 parts of Dioscorea opposita, 32 parts of Gleditsia sinensis, 36 parts of artificial bezoar, 30 parts of Prunus mume, 28 parts of Trichosanthes kirilowii, and 26 parts of maltose.

[0050] Example 3

[0051] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following parts by weight of traditional Chinese medicinal materials: 20 parts of Atractylodes lancea, 15 parts of Codonopsis pilosula, 20 parts of Astragalus complanatus, 20 parts of toad oil, 20 parts of Trogopterus xanthipes, 15 parts of Cynanchum paniculatum, 20 parts of amber, 15 parts of Dioscorea opposita, 20 parts of Gleditsia sinensis, 20 parts of artificial bezoar, 15 parts of Prunus mume, 15 parts of Trichosanthes kirilowii, and 15 parts of maltose.

[0052] Example 4

[0053] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following parts by weight of traditional Chinese medicinal materials: 40 parts of Atractylodes lancea, 30 parts of Codonopsis pilosula, 40 parts of Astragalus complanatus, 40 parts of toad oil, 40 parts of Trogopterus xanthipes, 30 parts of Cynanchum paniculatum, 40 parts of amber, 30 parts of Dioscorea opposita, 40 parts of Gleditsia sinensis, 40 parts of artificial bezoar, 30 parts of Prunus mume, 30 parts of Trichosanthes kirilowii, and 30 parts of maltose.

[0054] Example 5

[0055] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following parts by weight of traditional Chinese medicinal materials: 24 parts of Atractylodes lancea, 18 parts of Codonopsis pilosula, 26 parts of Astragalus complanatus, 36 parts of toad oil, 22 parts of Trogopterus xanthipes, 16 parts of Cynanchum paniculatum, 20 parts of amber, 18 parts of Dioscorea opposita, 22 parts of Gleditsia sinensis, 34 parts of artificial bezoar, 20 parts of Prunus mume, 22 parts of Trichosanthes kirilowii, and 20 parts of maltose.

[0056] Example 6

[0057] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following parts by weight of traditional Chinese medicinal materials: 36 parts of Atractylodes lancea, 30 parts of Codonopsis pilosula, 36 parts of Astragalus complanatus, 40 parts of toad oil, 32 parts of Trogopterus xanthipes, 25 parts of Cynanchum paniculatum, 30 parts of amber, 28 parts of Dioscorea opposita, 32 parts of Gleditsia sinensis, 40 parts of artificial bezoar, 22 parts of Prunus mume, 25 parts of Trichosanthes kirilowii, and 18 parts of maltose.

[0058] Example 7

[0059] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is made from the following parts by weight of traditional Chinese medicinal materials: 28 parts of Atractylodes lancea, 20 parts of Codonopsis pilosula, 30 parts of Astragalus complanatus, 36 parts of toad oil, 24 parts of Trogopterus xanthipes, 18 parts of Cynanchum paniculatum, 26 parts of amber, 20 parts of Dioscorea opposita, 28 parts of Gleditsia sinensis, 32 parts of artificial bezoar, 22 parts of Prunus mume, 24 parts of Trichosanthes kirilowii, and 16 parts of maltose.

[0060] Experimental Example 1

[0061] 1. Materials and Methods

[0062] 1.1 Laboratory Animals

[0063] Fifty healthy male SPF-grade ICR mice, weighing (20±2) g and aged 6-8 weeks, were housed at a temperature of (24±1) ℃ and a humidity of (50±5) %, with a 12h / 12h dark / light cycle. During the experiment, the mice had free access to food and water. The experiment was conducted after one week of acclimatization.

[0064] 1.2 Preparation of drug solution

[0065] The traditional Chinese medicine preparation of this invention consists of: 28 parts of Atractylodes lancea, 20 parts of Codonopsis pilosula, 30 parts of Astragalus complanatus, 36 parts of toad oil, 24 parts of Trogopterus xanthipes, 18 parts of Cynanchum paniculatum, 26 parts of amber, 20 parts of Dioscorea opposita, 28 parts of Gleditsia sinensis, 32 parts of artificial bezoar, 22 parts of Prunus mume, 24 parts of Trichosanthes kirilowii, and 16 parts of maltose. Each raw material is weighed according to the above weight (each part by weight is 1g). A refined concentrated solution with a drug concentration of 2g / mL (containing 2g of raw medicinal material per milliliter) is prepared according to the method described in Example 1. The solution is sterilized and stored at 4°C for later use.

[0066] Positive control drug: donepezil hydrochloride tablets (5mg / tablet), prepared with physiological saline to a concentration of 0.01mg / mL.

[0067] 1.3 Grouping and Administration

[0068] Mice were randomly divided into 5 groups (n=10 per group) after one week of acclimatization: blank control group, model group, positive control group (0.01 mg / mL donepezil hydrochloride solution, 0.1 mL / 10 g), low-dose group of the herbal composition of this invention (hereinafter referred to as low-dose group, 2 g / mL concentrated herbal solution, 0.1 mL / 10 g), and high-dose group of the herbal composition of this invention (hereinafter referred to as high-dose group, 2 g / mL concentrated herbal solution, 0.2 mL / 10 g). The blank control group and model group were administered physiological saline (0.1 mL / 10 g) by gavage. All groups were administered the medication by gavage once daily. Behavioral tests were performed after 4 weeks of administration.

[0069] 1.4 Construction of a cognitive impairment model

[0070] Thirty minutes before each behavioral test, all mice except the control group were injected intraperitoneally with scopolamine hydrobromide solution (0.2 mg / mL), at a dose of 2 mg / kg. The control group was injected with an equal volume of physiological saline.

[0071] 1.5 Behavioral Experiments

[0072] 1.5.1 Morris Water Maze Experiment

[0073] During week 5 of drug administration, the Morris water maze test was used to assess the spatial learning and memory abilities of mice in each group. The Morris water maze was a circular pool, 120 cm in diameter and 50 cm high, with black inner walls. The pool was divided into four quadrants by a cross-shaped intersection, with each quadrant's inner wall marked in red. The markings were of equal size. A platform was placed in the center of the target quadrant, submerged approximately 1 cm below the water surface. The temperature was controlled at (22±1)℃. The experiment was conducted at the same time each day. After swimming, the mice were promptly dried, and any excrement was removed from the pool to avoid affecting subsequent experiments. The experiment lasted for 7 days, twice a day.

[0074] Adaptation period: Mice were placed on a platform for 60 seconds for water entry training. Each training session was repeated twice. Each mouse was placed in the water from a different quadrant for 60 seconds. If a mouse could not find a platform, it was guided to stay on the platform for 20 seconds. The training period lasted for 1 day.

[0075] Orientation and navigation experiment: The platform was placed in quadrant IV. Mice were randomly selected and placed in any quadrant other than quadrant IV. The mice were held by the back and their faces were positioned to enter the water facing the pool wall. The time it took for the mice to find the platform by orienting themselves was defined as the escape latency. After finding the platform, the mice were allowed to stay for 10 seconds. If a mouse failed to find the platform within 120 seconds, the 120-second escape latency was defined as the escape latency, and the mouse was guided to the platform and allowed to stay for 20 seconds. This experiment was conducted for 5 days.

[0076] Space exploration experiment: When conducting this experiment, the platform was removed, and the mice were dropped into the water from the south point facing the pool wall. They swam freely for 120 seconds. The time when the mice first reached the original platform position (i.e., the latency period), the number of times the mice crossed the platform, and the time spent at the target phenomenon were recorded as indicators to assess their space exploration ability; the experiment lasted for 1 day.

[0077] 1.5.2 Thermal Stimulation Combined with Y-Maze Experiment

[0078] Six weeks after drug administration, a combined thermal stimulation and Y-maze test was performed to assess the spatial exploration ability of mice. The classic Y-maze consisted of three equal-length arms (30cm × 6cm × 15cm) made of black acrylic sheet. A 12W indicator light was mounted at the top of arm A, and heating plates (60–80℃) were placed at the bottom and junction of arms B and C. [See...] Figure 1The A-arm passage is the safe zone, while the B and C arm passages and their junction are the unsafe zones. The experiment is divided into an adaptation period, a learning period, and a testing period.

[0079] Adaptation period: Mice were placed in an unheated Y-maze to explore the environment freely for 1 day.

[0080] Learning period: Heat arms B and C to 65°C, and randomly place mice into either arm B or arm C. Set arm A as the target arm and light up the blue signal light. The learning behavior is considered to be completed when the mouse enters arm A 18 times out of 20 times. The number of learning times is recorded and the learning period is 1 day.

[0081] Testing period: Arms B and C were heated to 65°C, and the light on arm A was turned on. Arm A was set as the target arm, and the number of errors made by the mouse within 30 trials was recorded as a standard for testing the mouse's learning and memory abilities.

[0082] 1.6 Colorimetric determination of AChE content in the brain

[0083] After the heat stimulation combined with the Y-maze experiment, mice were fasted for 12 hours and samples were collected the following day. After perfusion with ice-cold saline, the animals were decapitated, and the brain, hippocampus, and cortex were separated. Brain tissue homogenates were prepared by adding 9 times the weight of protein lysis buffer to the hippocampus and cortex, respectively. After homogenization, the samples were centrifuged at 4°C, 3000 rpm for 15 minutes, and the supernatant was collected for analysis. The AChE activity assay was performed according to the instructions of the kit.

[0084] AChE activity = [Absorbance (as determined) - Absorbance (blank)] / [Absorbance (standard) - Absorbance (blank control)] × 100%

[0085] 1.7 Statistical Methods

[0086] Data statistical analysis and graphing were performed using Graphpad Prism 8.0 software. Results are expressed as mean ± standard deviation (Mean ± SD). One-way ANOVA was used to compare differences between groups, and P < 0.05 was considered statistically significant.

[0087] 2 Results

[0088] 2.1 Results of the Morris water maze experiment

[0089] The results of the positioning navigation experiment are as follows Figure 2As shown in Figure A, the escape latency of the control group mice gradually shortened as the experiment progressed, indicating that the training method was effective. During the experiment, the escape latency of the model group was significantly higher than that of the control group, indicating that the memory impairment model mice were successfully established. Compared with the model group, the escape latency of the positive control group and the low and high dose groups was consistently lower than that of the model group, with significant differences (P<0.01). There was no statistically significant difference in escape latency between the positive control group and the low and high dose groups (P>0.05). These results indicate that the traditional Chinese medicine preparation of this invention can effectively alleviate the learning and memory impairment caused by scopolamine, and the effect is comparable to that of the positive control drug.

[0090] Space exploration experiment results as follows Figure 2 As shown in BD. Compared with the control group, the latency time of mice in the model group was significantly increased (P<0.01); compared with the model group, the latency time of mice in each drug-treated group was significantly shortened (P<0.01). Figure 2 B. Compared with the control group, the number of times mice in the model group crossed the platform was significantly reduced (P<0.01); compared with the model group, the number of times mice in each drug-treated group crossed the platform was significantly increased (P<0.01), see... Figure 2 C. Compared with the control group, the time mice in the model group spent observing the target phenomenon was significantly reduced (P<0.01); compared with the model group, the time mice in each drug-treated group spent observing the target phenomenon was significantly increased (P<0.01), see [reference needed]. Figure 2 D.

[0091] 2.2 Results of the combined thermal stimulation and Y-maze experiment

[0092] There was no significant difference in the number of learning attempts among the different groups of mice (P>0.05), see [link to relevant documentation]. Figure 2 E. Compared with the control group, the number of errors in the model group mice was significantly increased (P<0.01); compared with the model group, the number of errors in each drug-treated group mice was significantly reduced (P<0.01). Figure 2 F.

[0093] 2.3 Results of AChE activity in the hippocampus and cortex of mice in each group

[0094] The results of AChE activity assay in the hippocampus of mice in each group are as follows: Figure 3 As shown in Figure A, compared with the blank group, the AChE activity in the hippocampus of mice in the model group was significantly increased (P<0.01); compared with the model group, the AChE activity in the hippocampus of mice in each drug-treated group was significantly decreased (P<0.01).

[0095] The results of AChE activity assay in the cortex of mice in each group are as follows: Figure 3As shown in Figure B, compared with the blank group, the AChE activity in the cortex of mice in the model group was significantly increased (P<0.05); compared with the model group, the AChE activity in the cortex of mice in each drug administration group was decreased, and the AChE activity in the cortex of mice in the positive control group and the high-dose group was significantly decreased (P<0.05).

[0096] 3. Conclusion

[0097] This invention uses scopolamine-induced learning and memory impairment in mice as a model to investigate the effect of the traditional Chinese medicine preparation of this invention on improving the learning and memory abilities of mice with cognitive impairment. The experimental results show that the traditional Chinese medicine preparation of this invention can significantly improve the learning and memory abilities of mice with cognitive impairment, mainly by significantly shortening the escape latency and spatial exploration latency, significantly increasing the number of platform crossings and the time spent in the target quadrant, significantly reducing the number of errors, and significantly inhibiting AChE activity in the hippocampus and cortex of the brain. These results indicate that the traditional Chinese medicine preparation of this invention has a significant therapeutic effect on improving or treating cognitive impairment, and its therapeutic effect is comparable to donepezil.

[0098] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A traditional Chinese medicine preparation for treating or improving cognitive impairment, characterized in that, The traditional Chinese medicine preparation is made from the following traditional Chinese medicinal materials in parts by weight: Atractylodes lancea 10-40 parts, Codonopsis pilosula 10-40 parts, Astragalus complanatus 10-40 parts, toad oil 10-40 parts, Trogopterus xanthipes 10-40 parts, Cynanchum paniculatum 10-40 parts, amber 10-40 parts, Dioscorea opposita 10-40 parts, Gleditsia sinensis 10-40 parts, artificial bezoar 10-40 parts, Prunus mume 10-40 parts, Trichosanthes kirilowii 10-40 parts, and maltose 10-40 parts.

2. A traditional Chinese medicine preparation for treating or improving cognitive impairment as described in claim 1, characterized in that, The traditional Chinese medicine preparation is made from the following parts by weight of Chinese medicinal materials: Atractylodes lancea 20-40 parts, Codonopsis pilosula 15-30 parts, Astragalus complanatus 20-40 parts, toad oil 20-40 parts, Trogopterus xanthipes 20-40 parts, Cynanchum paniculatum 15-30 parts, amber 20-40 parts, Dioscorea opposita 15-30 parts, Gleditsia sinensis 20-40 parts, artificial bezoar 20-40 parts, Prunus mume 15-30 parts, Trichosanthes kirilowii 15-30 parts, and maltose 15-30 parts.

3. A traditional Chinese medicine preparation for treating or improving cognitive impairment as described in claim 1, characterized in that, The traditional Chinese medicine preparation is made from the following parts by weight of Chinese medicinal materials: 28 parts of Atractylodes lancea, 20 parts of Codonopsis pilosula, 30 parts of Astragalus complanatus, 36 parts of toad oil, 24 parts of Trogopterus xanthipes, 18 parts of Cynanchum paniculatum, 26 parts of amber, 20 parts of Dioscorea opposita, 28 parts of Gleditsia sinensis, 32 parts of artificial bezoar, 22 parts of Prunus mume, 24 parts of Trichosanthes kirilowii, and 16 parts of maltose.

4. The traditional Chinese medicine preparation for treating or improving cognitive impairment as described in any one of claims 1 to 3, characterized in that, The traditional Chinese medicine preparation uses the stated weight proportions of Chinese medicinal materials as raw materials, supplemented with pharmaceutically acceptable excipients, and is prepared according to conventional preparation methods to produce an oral dosage form for treating or improving cognitive impairment. The dosage form includes any one of decoction, oral liquid, pill, powder, granule, capsule, tablet, and ointment.

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