Traditional Chinese medicine extract RM01 as well as application and preparation method thereof

Abstract

The present application provides methods of treating a neurodegenerative disease, such as Alzheimer's disease, in a patient by using a traditional Chinese medicine extract composition having an extract from a mixture comprising Radix Ophiopogonis, Fructus Lycii, Acorus tatarinowii, and Codonopsis pilosula. Compositions having such extracts and methods of making such compositions are also contemplated.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of priority of U.S. Provisional Application No. 63 / 410,388, filed on September 27, 2022, the entire content of which is incorporated herein by reference for all purposes. Technical Field

[0003] The present invention relates to the field of traditional Chinese medicine and compositions of traditional Chinese medicine extracts. Specifically, the present invention relates to a processed traditional Chinese medicine composition (such as an extract) RM01 comprising Ophiopogon Japonicus, Barbary Wolfberry, Rhizoma Acori Tatarinowii, and Codonopsis Pilosula, and the use of such compositions in the treatment of neurodegenerative diseases (e.g., Alzheimer's disease) and the improvement of cognition or memory. Background Art

[0004] In the United States, there are currently 6.2 million patients with Alzheimer's disease (AD). In addition to AD patients in the dementia stage, there are approximately 10 million people with mild cognitive impairment (MCI) (Cummings J et al., Translational Research & Clinical Interventions, 2022). The main symptoms of Alzheimer's disease are memory loss, difficulty performing familiar tasks, confusion about time or place, and challenges in planning or problem - solving, etc. (Alzheimer's Association). There is currently no cure for Alzheimer's disease. As of now, a total of 6 drugs have been approved by the FDA, including aducanumab, which was approved by the FDA in 2021 for the treatment of mild to moderate Alzheimer's disease. All of these treatments only slow down the progression of Alzheimer's disease but do not significantly stop its progression. Due to the increasing number of affected individuals and the increasing public health crisis caused by the global cost of care, there is an urgent need for therapies to prevent and improve the symptoms of Alzheimer's disease.

[0005] All references described herein are incorporated by reference in their entirety. Summary of the Invention

[0006] In some embodiments, a method of treating a neurodegenerative disease or disorder in an individual is provided, comprising administering to the individual a traditional Chinese medicine extract composition "RM01", which traditional Chinese medicine extract composition comprises an extract of a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula. In some embodiments, the mixture comprises from about 10% (w) to 70% (w) Ophiopogon japonicus, from about 10% (w) to 70% (w) Lycium barbarum, from about 10% (w) to 70% (w) Acorus tatarinowii, and from about 10% (w) to 70% (w) Codonopsis pilosula. In some embodiments, the mixture comprises from about 20% (w) to 30% (w) Ophiopogon japonicus, from about 20% (w) to 30% (w) Lycium barbarum, from about 20% (w) to 30% (w) Acorus tatarinowii, and from about 20% (w) to 30% (w) Codonopsis pilosula.

[0007] In some embodiments according to any of the above methods, the disease or disorder is Alzheimer's disease (AD). In some embodiments, the individual has mild AD, or has an MMSE score of 20 to 24. In some embodiments, the individual has moderate AD, or has an MMSE score of 13 to 20. In some embodiments, the individual has severe AD, or has an MMSE score of less than 12.

[0008] In some embodiments according to some of the above methods, the individual has a mild cognitive impairment (MCI) disease.

[0009] In some embodiments according to any of the above methods, the individual has memory loss.

[0010] In some embodiments according to any of the above methods, the traditional Chinese medicine extract composition RM01 is orally administered to the individual.

[0011] In some embodiments according to any of the above methods, the individual is a human.

[0012] In another aspect, the present application provides a traditional Chinese medicine extract composition "RM01", which comprises an extract of a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula. In some embodiments, the mixture comprises from about 10% (w) to 70% (w) Ophiopogon japonicus, from about 10% (w) to 70% (w) Lycium barbarum, from about 10% (w) to 70% (w) Acorus tatarinowii, and from about 10% (w) to 70% (w) Codonopsis pilosula. In some embodiments, the mixture comprises from about 20% (w) to 30% (w) Ophiopogon japonicus, from about 20% (w) to 30% (w) Lycium barbarum, from about 20% (w) to 30% (w) Acorus tatarinowii, and from about 20% (w) to 30% (w) Codonopsis pilosula.

[0013] In another aspect, the present application provides a method for preparing a traditional Chinese medicine extract composition from a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, the method comprising: i) adding a liquid to the mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula to obtain the mixture in the liquid; ii) heating the mixture in the liquid at a temperature approximately at the boiling point of the liquid for about 30 minutes to about 60 minutes; iii) collecting the liquid extract from the heated mixture; optionally, wherein the liquid is an aqueous solution, and further optionally the liquid is water.

[0014] In another aspect, the present application provides a method for preparing a traditional Chinese medicine extract composition from a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, the method comprising: i) adding water to the mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula to obtain the mixture in water; ii) heating the mixture in water at a temperature of about 100 °C for about 30 minutes to about 60 minutes; iii) collecting the liquid extract from the heated mixture.

[0015] In some embodiments, the mixture comprises from about 10% (w) to 70% (w) of Ophiopogon japonicus, from about 10% (w) to 70% (w) of Lycium barbarum, from about 10% (w) to 70% (w) of Acorus tatarinowii, and from about 10% (w) to 70% (w) of Codonopsis pilosula. In some embodiments, the mixture comprises from about 20% (w) to 30% (w) of Ophiopogon japonicus, from about 20% (w) to 30% (w) of Lycium barbarum, from about 20% (w) to 30% (w) of Acorus tatarinowii, and from about 20% (w) to 30% (w) of Codonopsis pilosula.

[0016] In another aspect, the present application provides a herbal extract composition prepared by the above method.

[0017] In another aspect, the present application provides a traditional Chinese medicine extract composition as described above, which further comprises an excipient. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 Two groups of mice evaluated by the Morris water maze are shown. APP / PS1 are double transgenic mice expressing the chimeric mouse / human amyloid precursor protein (Mo / HuAPP695swe) and mutant human presenilin 1 (PS1-dE9) (both targeted to CNS neurons). Both of these mutations are associated with early-onset Alzheimer's disease. One group is transgenic mice treated with the traditional Chinese medicine extract composition RM01.

[0019] Figure 2 The effect of treating patients with RM01 for 5 weeks is shown.

[0020] Figure 3 It is shown that RM01 reduces β-amyloid plaques in APP / PS1 mice. Detailed implementation mode

[0021] The present invention provides a herbal extract composition RM01 from a herbal mixture. The traditional Chinese medicine mixture comprises Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii and Codonopsis pilosula. The present invention also provides a method for preparing a traditional Chinese medicine extract composition from the traditional Chinese medicine mixture, wherein the method comprises the steps of heating the traditional Chinese medicine mixture in water and collecting the liquid extract formulated in water. The traditional Chinese medicine extract composition RM01 can be used for treating Alzheimer's disease or memory loss in an individual.

[0022] Definition

[0023] For the purpose of interpreting this specification, the following definitions will apply, and where appropriate, terms used in the singular will also include the plural and vice versa. If any definition set forth below conflicts with any document incorporated herein by reference, the defined definition shall control.

[0024] As used herein, "treatment" is a method for obtaining a beneficial or desired clinical outcome. As used herein, "treatment" encompasses any administration or application of a therapeutic agent for a disease in a mammal (including a human). For the purposes of the present invention, beneficial or desired clinical outcomes include, but are not limited to, any one or more of the following: alleviating one or more symptoms (e.g., Alzheimer's disease), reducing one or more symptoms of a disease, attenuating the degree of a disease, preventing or delaying disease recurrence, delaying or slowing disease progression, improving the disease state, inhibiting a disease or disease progression, or preventing disease development. "Treatment" also encompasses reducing the pathological consequences of a proliferative disease. The methods of the present invention contemplate any one or more of these aspects of treatment. In the context of Alzheimer's disease, the term "treatment" includes any one or all of the following: inhibiting the progression of memory loss, improving overall quality of life, and improving one or more symptoms associated with the disease (including Alzheimer's disease).

[0025] The "therapeutically effective amount" or "effective amount" in the present invention refers to the amount of the traditional Chinese medicine extract composition RM01 or pharmaceutical composition sufficient to improve the condition of a subject in need thereof without causing serious side effects.

[0026] As used herein, "pharmaceutically acceptable" or "pharmaceutically compatible" means a material that is not biologically or otherwise undesirable, e.g., the material can be incorporated into a pharmaceutical composition administered to a patient without causing any significant adverse biological effects and without interacting in a harmful manner with any other components of the composition containing the material. Pharmaceutically acceptable carriers or excipients preferably meet the required standards of toxicological and manufacturing testing and / or are included in the "Inactive Ingredient Guide" prepared by the U.S. Food and Drug Administration.

[0027] For any of the structural and functional properties described herein, methods for determining such properties are known in the art.

[0028] It should be understood that the aspects and embodiments of the invention described herein include "comprising the aspects and embodiments", "consisting of the aspects and embodiments", and "consisting essentially of the aspects and embodiments".

[0029] References herein to "about" a value or to a parameter include (and describe) variations that are directed to that value or parameter per se. For example, description of "about X" includes description of "X".

[0030] As used herein, the term "about" refers to the usual error range of the corresponding value that would be readily known to a person skilled in the art. References herein to "about" a value or a parameter include (and describe) embodiments that are directed to that value or parameter per se.

[0031] The term "about X-Y" as used herein has the same meaning as "about X to about Y".

[0032] Unless the context clearly dictates otherwise, as used herein and in the appended claims, the singular forms "a", "an", "or", and "the" also include plural referents.

[0033] Unless otherwise noted, technical terms are used in accordance with conventional usage.

[0034] Treatment method

[0035] The present application provides methods for treating neurodegenerative diseases (e.g., Alzheimer's disease). Some symptoms of the disease can include, but are not limited to, memory loss, cognitive impairment. In one aspect, there is provided a method for treating a disease in a subject in need thereof, the method comprising administering to the individual a traditional Chinese medicine extract composition as described herein. In some embodiments, the disease is Alzheimer's disease. In some embodiments, the traditional Chinese medicine extract composition comprises an extract of a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Radix Angelicae Pubescenti. In some embodiments, the traditional Chinese medicine extract composition comprises an extract of a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Radix Angelicae Pubescenti, wherein the traditional Chinese medicine extract composition is prepared by a method comprising the steps of: i) adding water to a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula to obtain a mixture in water; ii) heating the mixture in water at a temperature of about 100 °C for about 30 minutes to about 60 minutes; iii) collecting the liquid extract from the heated mixture.

[0036] In some embodiments, there is provided a method for treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition "RM01", the traditional Chinese medicine extract composition comprising an extract of a mixture comprising at least two or more traditional Chinese medicines selected from the group consisting of Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula.

[0037] In some embodiments, there is provided a method for treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition "RM01", the traditional Chinese medicine extract composition comprising an extract of a mixture comprising Ophiopogon japonicus and Lycium barbarum.

[0038] In some embodiments, there is provided a method for treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition "RM01", the traditional Chinese medicine extract composition comprising an extract of a mixture comprising Ophiopogon japonicus and Acorus tatarinowii.

[0039] In some embodiments, there is provided a method for treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition "RM01", the traditional Chinese medicine extract composition comprising an extract of a mixture comprising Ophiopogon japonicus and Codonopsis pilosula.

[0040] In some embodiments, there is provided a method for treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition "RM01", the traditional Chinese medicine extract composition comprising an extract of a mixture comprising Lycium barbarum and Acorus tatarinowii.

[0041] In some embodiments, a method of treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition “RM01” is provided, the traditional Chinese medicine extract composition comprising an extract of a mixture comprising wolfberry fruit and codonopsis pilosula.

[0042] In some embodiments, a method of treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition “RM01” is provided, the traditional Chinese medicine extract composition comprising an extract of a mixture comprising acorus tatarinowii and codonopsis pilosula.

[0043] In some embodiments, a method of treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition “RM01” is provided, the traditional Chinese medicine extract composition comprising an extract of a mixture comprising at least three or more traditional Chinese medicines selected from the group consisting of dwarf lilyturf tuber, wolfberry fruit, acorus tatarinowii and codonopsis pilosula.

[0044] In some embodiments, a method of treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition “RM01” is provided, the traditional Chinese medicine extract composition comprising an extract of a mixture comprising dwarf lilyturf tuber, wolfberry fruit and acorus tatarinowii.

[0045] In some embodiments, a method of treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition “RM01” is provided, the traditional Chinese medicine extract composition comprising an extract of a mixture comprising dwarf lilyturf tuber, acorus tatarinowii and codonopsis pilosula.

[0046] In some embodiments, a method of treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition “RM01” is provided, the traditional Chinese medicine extract composition comprising an extract of a mixture comprising wolfberry fruit, acorus tatarinowii and codonopsis pilosula.

[0047] In some embodiments, provided is a method of treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition “RM01”, the traditional Chinese medicine extract composition comprising an extract of a mixture comprising at least about 10% (w) of Ophiopogon japonicus, at least about 10% (w) of Lycium barbarum, at least about 10% (w) of Acorus tatarinowii, and at least about 10% of Codonopsis pilosula. The weight ratio (abbreviated as “w”) refers to the relative weight ratio of the component in the other traditional Chinese medicines comprised in the composition. In some embodiments, the other traditional Chinese medicines consist of Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula. In some embodiments, the mixture comprises about 10% (w) to 70% (w) of Ophiopogon japonicus, about 10% (w) to 70% (w) of Lycium barbarum, about 10% (w) to 70% (w) of Acorus tatarinowii, and about 10% (w) to 70% (w) of Codonopsis pilosula. In some embodiments, the mixture comprises about 20% (w) to 30% (w) of Ophiopogon japonicus, about 20% (w) to 30% (w) of Lycium barbarum, about 20% (w) to 30% (w) of Acorus tatarinowii, and about 20% (w) to 30% (w) of Codonopsis pilosula. In some embodiments, the individual has mild AD, or has an MMSE score of 20 to 24. In some embodiments, the individual has moderate AD, or has an MMSE score of 13 to 20. In some embodiments, the individual has severe AD, or has an MMSE score of less than 12. In some embodiments, the individual has mild cognitive impairment (MCI) disease. In some embodiments, the individual has memory loss.

[0048] In some embodiments, provided is a method of treating a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition “RM01”, the traditional Chinese medicine extract composition comprising an extract of a mixture comprising Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, wherein the weight ratio of Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula is about 1:1:1:1.

[0049] In some embodiments, provided is a method of improving symptoms associated with a neurodegenerative disease (e.g., Alzheimer's disease) in an individual by administering (e.g., orally administering) a traditional Chinese medicine extract composition “RM01”, the traditional Chinese medicine extract composition comprising an extract of a mixture comprising Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula. In some embodiments, the symptoms include memory loss. In some embodiments, the symptoms include the individual's inability to follow instructions. In some embodiments, the systemic improvement is indicated by an increase in the MMSE score after treatment. In some embodiments, the individual shows an increase in the MMSE score of at least 1 point, 2 points, 3 points, 4 points, 5 points, or 6 points after treatment.

[0050] In some embodiments according to any of the above methods, the subject is a human. In some embodiments, the subject is female. In other embodiments, the subject is male. In some embodiments, the subject is in need of treatment for Alzheimer's disease. In some embodiments, the subject is diagnosed with mild Alzheimer's disease, moderate Alzheimer's disease, or severe Alzheimer's disease.

[0051] In some embodiments according to any of the above methods, the age of the individual is between about 50 years old and about 100 years old. In some embodiments, the age of the individual is any of the following: between about 50 years old and about 60 years old, between about 60 years old and about 70 years old, between about 70 years old and about 80 years old, between about 80 years old and about 90 years old, or between about 90 years old and about 100 years old. For memory decline and mild cognitive impairment (MCI), the age of the individual is between about 30 years old and about 100 years old. In some embodiments, the age of the individual is any of the following: between about 30 years old and about 40 years old, between about 40 years old and about 50 years old, between about 50 years old and about 60 years old, between about 60 years old and about 70 years old, between about 70 years old and about 80 years old, between about 80 years old and about 90 years old, or between about 90 years old and about 100 years old.

[0052] In some embodiments, the subject has an MMSE score below 25 before treatment. In some embodiments, the subject has an MMSE score of about 20 to about 24. In some embodiments, the subject has an MMSE score of any of about 20, 21, 22, 23, or 24. In some embodiments, the subject has an MMSE score of about 13 to about 20. In some embodiments, the subject has an MMSE score of any of about 13, 14, 15, 16, 17, 18, 19, or 20. In some embodiments, the subject has an MMSE score of about 12 or lower. In some embodiments, the subject has an MMSE score of any of about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.

[0053] In some embodiments, the subject has been diagnosed with Alzheimer's disease, and one or more symptoms associated with Alzheimer's disease have not been alleviated by previous treatment. In some embodiments, the subject has been diagnosed with Alzheimer's disease, and previous treatment has not alleviated any symptoms associated with Alzheimer's disease. Exemplary existing therapies include, but are not limited to, aducanumab, memantine, and / or donepezil.

[0054] In one aspect, there is provided a method of ameliorating the symptoms of a neurodegenerative disease in an individual, the method comprising administering to the individual a therapeutically effective amount of a traditional Chinese medicine extract composition according to any of the above embodiments. In some embodiments, the disease is Alzheimer's disease. In some embodiments, there is provided a method of enhancing the cognitive ability of an individual suffering from Alzheimer's disease, the method comprising administering to the individual a therapeutically effective amount of a traditional Chinese medicine extract composition according to any of the above embodiments.

[0055] In some embodiments, the subject receives oral administration of the traditional Chinese medicine extract.

[0056] In some embodiments of any of the above methods, the MMSE score of the subject increases after administration of the traditional Chinese medicine extract. In some embodiments, the MMSE score of the subject receiving administration of the traditional Chinese medicine extract increases compared to the corresponding individual not receiving administration of the traditional Chinese medicine extract. In some embodiments, the MMSE score of the subject receiving administration of the traditional Chinese medicine extract increases compared to the corresponding individual receiving aducanumab, memantine, and / or donepezil. In some embodiments, the MMSE score of at least 50%, 60%, 70%, 80%, or 90% of the subjects increases after administration of the traditional Chinese medicine extract. In some embodiments, the MMSE score of at least 50%, 60%, 70%, 80%, or 90% of the subjects receiving administration of the traditional Chinese medicine extract increases compared to the corresponding individual not receiving administration of the traditional Chinese medicine extract. In some embodiments, the MMSE score of at least 50%, 60%, 70%, 80%, or 90% of the subjects receiving administration of the traditional Chinese medicine extract increases compared to the corresponding individual receiving aducanumab, memantine, and / or donepezil.

[0057] In some embodiments according to any of the above methods, wherein the individual has an MMSE score of 0 to about 9 before receiving the traditional Chinese medicine extract, the MMSE score of the individual increases by about 1 to 5 points, about 5 to 10 points, about 10 to 15 points, or about 15 to 20 points after receiving the traditional Chinese medicine extract. In some embodiments, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by about 1 to 5 points, about 5 to 10 points, about 10 to 15 points, or about 15 to 20 points compared to the corresponding individual not receiving the traditional Chinese medicine extract. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by about 1 to 5 points, about 5 to 10 points, about 10 to 15 points, or about 15 to 20 points compared to the corresponding individual receiving aducanumab, memantine, and / or donepezil. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by any of the following scores compared to the corresponding individual not receiving the traditional Chinese medicine extract: 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, 10 points, 11 points, 12 points, 13 points, 14 points, or 15 points. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, 10 points, 11 points, 12 points, 13 points, 14 points, or 15 points compared to the corresponding individual receiving aducanumab, memantine, and / or donepezil.

[0058] In some embodiments according to any of the above methods, wherein the individual has an MMSE score of about to about 14 before receiving the traditional Chinese medicine extract, the MMSE score of the individual increases by about 1 to 5 points, about 5 to 10 points, or about 10 to 15 points after receiving the traditional Chinese medicine extract. In some embodiments, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by about 1 to 5 points, about 5 to 10 points, or about 10 to 15 points compared to the corresponding individual not receiving the traditional Chinese medicine extract. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by about 1 to 5 points, about 5 to 10 points, or about 10 to 15 points compared to the corresponding individual receiving aducanumab, memantine, and / or donepezil. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by any of the following scores compared to the corresponding individual not receiving the traditional Chinese medicine extract: 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, 10 points, 11 points, 12 points, 13 points, 14 points, or 15 points. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, 10 points, 11 points, 12 points, 13 points, 14 points, or 15 points compared to the corresponding individual receiving aducanumab, memantine, and / or donepezil.

[0059] In some embodiments according to any of the above methods, wherein the individual has an MMSE score of 15 to about 19 before receiving the traditional Chinese medicine extract, the MMSE score of the individual increases by about 1 to 5 points, or about 5 to 10 points after receiving the traditional Chinese medicine extract. In some embodiments, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by about 1 to 5 points, or about 5 to 10 points compared to the corresponding individual not receiving the traditional Chinese medicine extract. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by about 1 to 5 points, or about 5 to 10 points compared to the corresponding individual receiving aducanumab, memantine, and / or donepezil. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by any of the following scores compared to the corresponding individual not receiving the traditional Chinese medicine extract: 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, or 10 points. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increases by 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, or 10 points compared to the corresponding individual receiving aducanumab, memantine, and / or donepezil.

[0060] In some embodiments according to any of the above methods, where the individual had an MMSE score of 20 to about 24 before receiving the traditional Chinese medicine extract, the MMSE score of the individual increased by about 1 to 5 points after receiving the traditional Chinese medicine extract. In some embodiments, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increased by about 1 to 5 points compared to the corresponding individual who did not receive the traditional Chinese medicine extract. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increased by about 1 to 5 points compared to the corresponding individual receiving aducanumab, memantine, and / or donepezil. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increased by any of the following scores compared to the corresponding individual who did not receive the traditional Chinese medicine extract: 1 point, 2 points, 3 points, 4 points, or 5 points. In some embodiments according to any of the above methods, the MMSE score of the individual receiving the administration of the traditional Chinese medicine extract increased by 1 point, 2 points, 3 points, 4 points, or 5 points compared to the corresponding individual receiving aducanumab, memantine, and / or donepezil.

[0061] In some embodiments, MRI and / or PET are used to evaluate the differences in beta-amyloid and Tau proteins in the individual. In some embodiments, ADAS-Cog13, ADCS-ADL, and / or MoCA are used for cognitive assessment. In some embodiments, the change in the ADAS-Cog13 score of the individual is less than -4 (e.g., -4, -5, -6, -7, -8, -9, -10).

[0062] In some embodiments, RM01 is administered at least once a day (e.g., once a day or twice a day) for at least about one day, two days, or three days. In some embodiments, RM01 is administered for at least one week, two weeks, three weeks, four weeks, or five weeks. In some embodiments, RM01 is administered once a day or twice a day. In some embodiments, RM01 is administered once every two days or once every three days. In some embodiments, RM01 is administered once a week or twice a week. In some embodiments, RM01 is administered for at least one month or two months. In some embodiments, RM01 is administered for at least one week, two weeks, three weeks, four weeks, or five weeks.

[0063] In some embodiments, the individual is a human patient. In some embodiments, the age of the individual is at least 50 years old. In some embodiments, the individual has Alzheimer's disease, optionally where the Alzheimer's disease cannot be alleviated by current drug treatment. In some embodiments, the individual has mild or severe Alzheimer's disease. In some embodiments, the individual has a patient life expectancy of more than 12 months.

[0064] The present application further provides a method for reducing or removing amyloid plaques in an individual's brain, which includes administering to the individual the traditional Chinese medicine extract composition "RM01" as described above. In some embodiments, RM01 includes an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula. In some embodiments, the mixture contains about 10% (w) to 70% (w) of Ophiopogon japonicus, about 10% (w) to 70% (w) of Lycium barbarum, about 10% (w) to 70% (w) of Acorus tatarinowii, and about 10% (w) to 70% (w) of Codonopsis pilosula. In some embodiments, the mixture contains about 20% (w) to 30% (w) of Ophiopogon japonicus, about 20% (w) to 30% (w) of Lycium barbarum, about 20% (w) to 30% (w) of Acorus tatarinowii, and about 20% (w) to 30% (w) of Codonopsis pilosula. In some embodiments, the weight ratio of Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula is about 1:1:1:1. In some embodiments, RM01 is administered once a day or twice a day, optionally wherein RM01 is administered orally. In some embodiments, RM01 is administered for at least about one week, two weeks, three weeks, four weeks, or five weeks. In some embodiments, RM01 is administered for at least about one month. In some embodiments, the disease or disorder is Alzheimer's disease (AD). In some embodiments, the individual has mild AD, or has an MMSE score of 20 to 24. In some embodiments, the individual has moderate AD, or has an MMSE score of 13 to 20. In some embodiments, the individual has severe AD, or has an MMSE score of less than 12. In some embodiments, the individual has mild cognitive impairment (MCI) disease. In some embodiments, the individual has memory loss. In some embodiments, the individual is a human.

[0065] The present application further provides a method for treating, delaying or preventing a neurodegenerative disease or disorder (e.g., Alzheimer's disease) in an individual, comprising administering to the individual the traditional Chinese medicine extract composition "RM01" as described above. In some embodiments, RM01 comprises an extract of a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii and Codonopsis pilosula. In some embodiments, the mixture comprises from about 10% (w) to 70% (w) of Ophiopogon japonicus, from about 10% (w) to 70% (w) of Lycium barbarum, from about 10% (w) to 70% (w) of Acorus tatarinowii and from about 10% (w) to 70% (w) of Codonopsis pilosula. In some embodiments, the mixture comprises from about 20% (w) to 30% (w) of Ophiopogon japonicus, from about 20% (w) to 30% (w) of Lycium barbarum, from about 20% (w) to 30% (w) of Acorus tatarinowii and from about 20% (w) to 30% (w) of Codonopsis pilosula. In some embodiments, the weight ratio of Lycium barbarum, Acorus tatarinowii and Codonopsis pilosula is about 1:1:1:1. In some embodiments, RM01 is administered once or twice a day, optionally wherein RM01 is administered orally. In some embodiments, RM01 is administered for at least about one week, two weeks, three weeks, four weeks or five weeks. In some embodiments, RM01 is administered for at least about one month. In some embodiments, the individual has mild AD, or has an MMSE score of 20 to 24. In some embodiments, the individual has moderate AD, or has an MMSE score of 13 to 20. In some embodiments, the individual has severe AD, or has an MMSE score of less than 12. In some embodiments, the individual has mild cognitive impairment (MCI) disease. In some embodiments, the individual has memory loss. In some embodiments, the individual is a human.

[0066] The present application further provides a method for improving the memory of an individual, which includes administering to the individual the traditional Chinese medicine extract composition "RM01" as described above. In some embodiments, RM01 includes an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula. In some embodiments, the mixture contains about 10% (w) to 70% (w) of Ophiopogon japonicus, about 10% (w) to 70% (w) of Lycium barbarum, about 10% (w) to 70% (w) of Acorus tatarinowii, and about 10% (w) to 70% (w) of Codonopsis pilosula. In some embodiments, the mixture contains about 20% (w) to 30% (w) of Ophiopogon japonicus, about 20% (w) to 30% (w) of Lycium barbarum, about 20% (w) to 30% (w) of Acorus tatarinowii, and about 20% (w) to 30% (w) of Codonopsis pilosula. In some embodiments, the weight ratio of Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula is about 1:1:1:1. In some embodiments, RM01 is administered once a day or twice a day, optionally wherein RM01 is administered orally. In some embodiments, RM01 is administered for at least about one week, two weeks, three weeks, four weeks, or five weeks. In some embodiments, RM01 is administered for at least about one month. In some embodiments, the disease or disorder is Alzheimer's disease (AD). In some embodiments, the individual has mild AD, or has an MMSE score of 20 to 24. In some embodiments, the individual has moderate AD, or has an MMSE score of 13 to 20. In some embodiments, the individual has severe AD, or has an MMSE score of less than 12. In some embodiments, the individual has mild cognitive impairment (MCI) disease. In some embodiments, the individual has memory loss. In some embodiments, the individual is a human.

[0067] Alzheimer's disease

[0068] The biological definition of Alzheimer's disease (AD) is the presence of plaques containing β-amyloid protein and neurofibrillary tangles containing tau protein. AD is a hereditary and sporadic neurodegenerative disease that causes amnestic cognitive impairment in its prototypical presentation and non-amnestic cognitive impairment in its less common variants. AD is a common cause of acquired cognitive impairment in middle age and old age, but its clinical impact is modified by the interaction of other neurodegenerative and cerebrovascular disorders. This introduction defines the biological mechanism of AD as a brain disease that stems from the complex interaction between the loss of synaptic homeostasis and dysfunction of the highly associated endosomal / lysosomal clearance pathway, in which the precursors, aggregates, and post-translational modification products of Aβ and tau play important roles. Currently, treatment research for AD still has difficulty finding targets that can significantly change the clinical course of patients within this framework. See Knopman et al., Alzheimer disease. Nat Rev Dis Primers 7, 33 (2021).

[0069] Ophiopogon japonicus

[0070] Ophiopogon japonicus (Thunb.) Ker-Gawl, also known as "Ophiopogon japonicus" in Chinese, is spindle-shaped with tapering ends, 1.5 to 3 cm in length. It is naturally distributed in provinces such as Sichuan, Yunnan, Shanxi, and Hunan in China. Ophiopogon japonicus has a firm texture, is light yellow to white in color, and is generally spindle-shaped with pointed ends. The raw product of Ophiopogon japonicus has a slightly pungent smell, is pungent, bitter, and slightly numb in taste, and is non-toxic; however, its decocted product has a fragrant smell.

[0071] Lycium barbarum

[0072] Lycium barbarum L., also known as "Lycium barbarum" in Chinese, is naturally distributed in the northeastern region of China. The raw material of Lycium barbarum has a firm texture, is red or light brown on the surface, is spindle-shaped or oval in shape, about 6 to 20 mm in length and about 3 to 10 mm in width. The raw product of Lycium barbarum has a sweet taste. It has a long history of being used as a food supplement.

[0073] Acorus tatarinowii

[0074] Rhizoma Acori Tatarinowii, also known as "calamus" in Chinese. There are three common original sources: Rhizoma Acori Tatarinowii, Anemone altaica Fisch. ex C.A.Mey (Ranunculaceae), and Acorus calamus (a closely related species of the same genus), which are native to East Asia. The main original source for Rhizoma Acori Tatarinowii used in medicine is the dried roots and rhizomes of Notopterygium incisum Tncisum Ting ex H.Chang or Notopterygium forbesii Boiss. The rhizome of the raw product of Rhizoma Acori Tatarinowii has a firm texture, is brownish on the surface, is long cylindrical in shape, and has ring-shaped protrusions. The raw product of Rhizoma Acori Tatarinowii has a fragrant smell, is slightly bitter and pungent in taste. The fibrous roots and soil usually need to be removed before slicing Rhizoma Acori Tatarinowii. In some embodiments, the Rhizoma Acori Tatarinowii used herein refers to its roots.

[0075] Codonopsis pilosula

[0076] Codonopsis Pilosula, also known as dangshen in Chinese. Its root is slightly cylindrical and slightly curved. Its length is usually about 10 cm to 35 cm, and its diameter is 0.4 cm to 2 cm, presenting a light yellow to light gray color. Transverse wrinkles can be seen on the surface. Codonopsis Pilosula is naturally distributed in provinces such as Sichuan, Hubei, and Anhui in China. The raw Codonopsis Pilosula has a fragrant smell and a slightly sweet taste. When Codonopsis Pilosula is used as medicine, its dried root is usually taken, which refers to its root in this application.

[0077] In some embodiments, the roots of Acorus tatarinowii and / or Codonopsis Pilosula used are fresh products. In some embodiments, the Acorus tatarinowii and / or Codonopsis Pilosula used are dried roots.

[0078] Traditional Chinese medicine mixture composition and traditional Chinese medicine extract composition

[0079] This application provides a traditional Chinese medicine extract composition RM01, which includes an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis Pilosula.

[0080] In some embodiments, a traditional Chinese medicine extract composition RM01 is provided, which includes an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis Pilosula, wherein the mixture contains about 10% (w) to 70% (w) of Ophiopogon japonicus, about 10% (w) to 70% (w) of Lycium barbarum, about 10% (w) to 70% (w) of Acorus tatarinowii, and about 10% (w) to 70% (w) of Codonopsis Pilosula.

[0081] In one aspect, a composition including a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis Pilosula (hereinafter referred to as "traditional Chinese medicine mixture") is provided. Through certain extraction methods, a traditional Chinese medicine extract composition can be obtained from the traditional Chinese medicine mixture. Therefore, in another aspect, a traditional Chinese medicine extract composition is provided, which includes an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis Pilosula ("traditional Chinese medicine mixture").

[0082] In some embodiments, the weight percentage of Ophiopogon japonicus in the traditional Chinese medicine mixture is about 1% to 97%. In some embodiments, the weight percentage of Ophiopogon japonicus in the traditional Chinese medicine mixture is about 5% to 85%. In some embodiments, the weight percentage of Ophiopogon japonicus in the traditional Chinese medicine mixture is about 10% to 70%. In some embodiments, the weight percentage of Ophiopogon japonicus in the traditional Chinese medicine mixture is about 10% to 70%. In some embodiments, the weight percentage of Ophiopogon japonicus in the traditional Chinese medicine mixture is any one of the following: about 1% to 97%, about 5% to 85%, about 10% to 70%, about 15% to 55%, about 20% to 40%, or about 20% to 30%. In some embodiments, the weight percentage of Ophiopogon japonicus in the traditional Chinese medicine mixture is any one of the following: about 8% to 15%, about 10% to 20%, about 60% to 70%, about 55% to 70%, or about 55% to 80%. In some embodiments, the weight percentage of Ophiopogon japonicus in the traditional Chinese medicine mixture is about any one of the following: about 1% to 5%, about 5% to 10%, about 10% to 15%, about 15% to 20%, about 20% to 25%, about 25% to 30%, about 30% to 35%, about 35% to 40%, about 40% to 45%, about 45% to 50%, about 50% to 55%, about 55% to 60%, about 60% to 65%, about 65% to 70%, about 70% to 75%, about 75% to 80%, about 80% to 85%, about 85% to 90%, about 90% to 95%, or about 95% to 97%. In some embodiments, the weight percentage of Ophiopogon japonicus in the traditional Chinese medicine mixture is about any one of the following: about 1%, about 5%, about 10%, about 12.5%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 62.5%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95% or about 97%.

[0083] In some embodiments, the weight percentage of Lycium barbarum in the traditional Chinese medicine mixture is about 1% to 97%. In some embodiments, the weight percentage of Lycium barbarum in the traditional Chinese medicine mixture is about 5% to 85%. In some embodiments, the weight percentage of Lycium barbarum in the traditional Chinese medicine mixture is about 10% to 70%. In some embodiments, the weight percentage of Lycium barbarum in the traditional Chinese medicine mixture is about 10% to 70%. In some embodiments, the weight percentage of Lycium barbarum in the traditional Chinese medicine mixture is any one of the following: about 1% to 97%, about 5% to 85%, about 10% to 70%, about 15% to 55%, about 20% to 40%, or about 20% to 30%. In some embodiments, the weight percentage of Lycium barbarum in the traditional Chinese medicine mixture is any one of the following: about 8% to 15%, about 10% to 20%, about 60% to 70%, about 55% to 70%, or about 55% to 80%. In some embodiments, the weight percentage of Lycium barbarum in the traditional Chinese medicine mixture is about any one of the following: about 1% to 5%, about 5% to 10%, about 10% to 15%, about 15% to 20%, about 20% to 25%, about 25% to 30%, about 30% to 35%, about 35% to 40%, about 40% to 45%, about 45% to 50%, about 50% to 55%, about 55% to 60%, about 60% to 65%, about 65% to 70%, about 70% to 75%, about 75% to 80%, about 80% to 85%, about 85% to 90%, about 90% to 95%, or about 95% to 97%. In some embodiments, the weight percentage of Lycium barbarum in the traditional Chinese medicine mixture is about any one of the following: about 1%, about 5%, about 10%, about 12.5%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 62.5%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95% or about 97%.

[0084] In some embodiments, the weight percentage of Acorus tatarinowii in the traditional Chinese medicine mixture is about 1% to 97%. In some embodiments, the weight percentage of Acorus tatarinowii in the traditional Chinese medicine mixture is about 5% to 85%. In some embodiments, the weight percentage of Acorus tatarinowii in the traditional Chinese medicine mixture is about 10% to 70%. In some embodiments, the weight percentage of Acorus tatarinowii in the traditional Chinese medicine mixture is about 10% to 70%. In some embodiments, the weight percentage of Acorus tatarinowii in the traditional Chinese medicine mixture is any one of the following: about 1% to 97%, about 5% to 85%, about 10% to 70%, about 15% to 55%, about 20% to 40%, or about 20% to 30%. In some embodiments, the weight percentage of Acorus tatarinowii in the traditional Chinese medicine mixture is any one of the following: about 8% to 15%, about 10% to 20%, about 60% to 70%, about 55% to 70%, or about 55% to 80%. In some embodiments, the weight percentage of Acorus tatarinowii in the traditional Chinese medicine mixture is about any one of the following: about 1% to 5%, about 5% to 10%, about 10% to 15%, about 15% to 20%, about 20% to 25%, about 25% to 30%, about 30% to 35%, about 35% to 40%, about 40% to 45%, about 45% to 50%, about 50% to 55%, about 55% to 60%, about 60% to 65%, about 65% to 70%, about 70% to 75%, about 75% to 80%, about 80% to 85%, about 85% to 90%, about 90% to 95%, or about 95% to 97%. In some embodiments, the weight percentage of Acorus tatarinowii in the traditional Chinese medicine mixture is about any one of the following: about 1%, about 5%, about 10%, about 12.5%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 62.5%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95% or about 97%.

[0085] In some embodiments, the weight percentage of Codonopsis pilosula in the traditional Chinese medicine mixture is about 1% to 97%. In some embodiments, the weight percentage of Codonopsis pilosula in the traditional Chinese medicine mixture is about 5% to 85%. In some embodiments, the weight percentage of Codonopsis pilosula in the traditional Chinese medicine mixture is about 10% to 70%. In some embodiments, the weight percentage of Codonopsis pilosula in the traditional Chinese medicine mixture is about 10% to 70%. In some embodiments, the weight percentage of Codonopsis pilosula in the traditional Chinese medicine mixture is any one of the following: about 1% to 97%, about 5% to 85%, about 10% to 70%, about 15% to 55%, about 20% to 40%, or about 20% to 30%. In some embodiments, the weight percentage of Codonopsis pilosula in the traditional Chinese medicine mixture is any one of the following: about 8% to 15%, about 10% to 20%, about 60% to 70%, about 55% to 70%, or about 55% to 80%. In some embodiments, the weight percentage of Codonopsis pilosula in the traditional Chinese medicine mixture is about any one of the following: about 1% to 5%, about 5% to 10%, about 10% to 15%, about 15% to 20%, about 20% to 25%, about 25% to 30%, about 30% to 35%, about 35% to 40%, about 40% to 45%, about 45% to 50%, about 50% to 55%, about 55% to 60%, about 60% to 65%, about 65% to 70%, about 70% to 75%, about 75% to 80%, about 80% to 85%, about 85% to 90%, about 90% to 95%, or about 95% to 97%. In some embodiments, the weight percentage of Codonopsis pilosula in the traditional Chinese medicine mixture is about any one of the following: about 1%, about 5%, about 10%, about 12.5%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 62.5%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95% or about 97%.

[0086] In some embodiments, the traditional Chinese medicine mixture comprises Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii and Codonopsis pilosula, wherein the weight ratio of Ophiopogon japonicus to Lycium barbarum is any one of the following: about 20:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10 or about 1:20. In some embodiments, the weight ratio of Ophiopogon japonicus to Lycium barbarum is about any one of the following: about 5:1, about 1:1 or about 1:5.

[0087] In some embodiments, the traditional Chinese medicine mixture comprises Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, wherein the weight ratio of Ophiopogon japonicus to Acorus tatarinowii is any one of the following: about 20:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, or about 1:20. In some embodiments, the weight ratio of Ophiopogon japonicus to Acorus tatarinowii is about any one of the following: about 5:1, about 1:1, or about 1:5.

[0088] In some embodiments, the traditional Chinese medicine mixture comprises Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, wherein the weight ratio of Ophiopogon japonicus to Codonopsis pilosula is any one of the following: about 20:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, or about 1:20. In some embodiments, the weight ratio of Ophiopogon japonicus to Codonopsis pilosula is about any one of the following: about 5:1, about 1:1, or about 1:5.

[0089] In some embodiments, the traditional Chinese medicine mixture comprises Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, wherein the weight ratio of Lycium barbarum to Acorus tatarinowii is any one of the following: about 20:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, or about 1:20. In some embodiments, the weight ratio of Lycium barbarum to Acorus tatarinowii is about any one of the following: about 5:1, about 1:1, or about 1:5.

[0090] In some embodiments, the traditional Chinese medicine mixture comprises Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, wherein the weight ratio of Lycium barbarum to Codonopsis pilosula is any one of the following: about 20:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, or about 1:20. In some embodiments, the weight ratio of Lycium barbarum to Codonopsis pilosula is about any one of the following: about 5:1, about 1:1, or about 1:5.

[0091] In some embodiments, the traditional Chinese medicine mixture comprises Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, wherein the weight ratio of Acorus tatarinowii to Codonopsis pilosula is any one of the following: about 20:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, or about 1:20. In some embodiments, the weight ratio of Notopterygium incisum to Codonopsis pilosula is any one of the following: about 5:1, about 1:1, or about 1:5.

[0092] In some embodiments, the traditional Chinese medicine mixture comprises Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, wherein the weight ratio of Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula is any one of the following: about 1:1:1:2, about 1:1:2:1, about 1:2:1:1, about 2:1:1:1, about 1:1:2:2, about 1:2:1:2, about 1:2:2:1, about 2:1:2:1, about 2:2:1:1, about 2:1:1:2, about 1:2:2:2, about 2:1:2:2, about 2:2:1:2, about 2:2:2:1, about 1:1:1:3, about 1:1:3:1, about 1:3:1:1, about 3:1:1:1, about 1:1:3:3, about 1:3:1:3, about 1:3:3:1, about 3:1:3:1, about 3:3:1:1, about 3:1:1:3, about 1:3:3:3, about 3:1:3:3, about 3:3:1:3, about 3:3:3:1, about 1:1:1:4, about 1:1:4:1, about 1:4:1:1, about 4:1:1:1, about 1:1:4:4, about 1:4:1:4, about 1:4:4:1, about 4:1:4:1, about 4:4:1:1, about 4:1:1:4, about 1:4:4:4, about 4:1:4:4, about 4:4:1:4, about 4:4:4:1, about 1:1:1:5, about 1:1:5:1, about 1:5:1:1, about 5:1:1:1, about 1:1:5:5, about 1:5:1:5, about 1:5:5:1, about 5:1:5:1, about 5:5:1:1, about 5:1:1:5, about 1:5:5:5, about 5:1:5:5, about 5:5:1:5, or about 5:5:5:1.

[0093] In one aspect, there is provided a traditional Chinese medicine extract composition, which comprises an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula. In some embodiments of the above traditional Chinese medicine extract composition, the mixture comprises from about 1% (w) to 97% (w) of Ophiopogon japonicus, from about 1% (w) to 97% (w) of Lycium barbarum, from about 1% (w) to 97% (w) of Acorus tatarinowii, and from about 1% (w) to 97% (w) of Codonopsis pilosula. In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises from about 5% (w) to 85% (w) of Ophiopogon japonicus, from about 5% (w) to 85% (w) of Lycium barbarum, from about 5% (w) to 85% (w) of Acorus tatarinowii, and from about 5% (w) to 85% (w) of Codonopsis pilosula. In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises from about 10% (w) to 70% (w) of Ophiopogon japonicus, from about 10% (w) to 70% (w) of Lycium barbarum, from about 10% (w) to 70% (w) of Acorus tatarinowii, and from about 10% (w) to 70% (w) of Codonopsis pilosula. In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises from about 15% (w) to 55% (w) of Ophiopogon japonicus, from about 15% (w) to 55% (w) of Lycium barbarum, from about 15% (w) to 55% (w) of Acorus tatarinowii, and from about 15% (w) to 55% (w) of Codonopsis pilosula. In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises from about 20% (w) to 40% (w) of Ophiopogon japonicus, from about 20% (w) to 40% (w) of Lycium barbarum, from about 20% (w) to 40% (w) of Acorus tatarinowii, and from about 20% (w) to 40% (w) of Codonopsis pilosula. In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises from about 20% (w) to 30% (w) of Ophiopogon japonicus, from about 20% (w) to 30% (w) of Lycium barbarum, from about 20% (w) to 30% (w) of Acorus tatarinowii, and from about 20% (w) to 30% (w) of Codonopsis pilosula. In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises about 25% (w) of Ophiopogon japonicus, about 25% (w) of Lycium barbarum, about 25% (w) of Acorus tatarinowii, and about 25% (w) of Codonopsis pilosula.

[0094] In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises from about 55% (w) to 80% (w) of Ophiopogon japonicus, from about 8% (w) to 15% (w) of Lycium barbarum, from about 8% (w) to 15% (w) of Acorus tatarinowii, and from about 8% (w) to 15% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises from about 55% (w) to 70% (w) of Ophiopogon japonicus, from about 10% (w) to 15% (w) of Lycium barbarum, from about 10% (w) to 15% (w) of Acorus tatarinowii, and from about 10% (w) to 15% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises from about 60% (w) to 70% (w) of Ophiopogon japonicus, from about 10% (w) to 20% (w) of Lycium barbarum, from about 10% (w) to 20% (w) of Acorus tatarinowii, and from about 10% (w) to 20% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises from about 60% (w) to 65% (w) of Ophiopogon japonicus, from about 10% (w) to 15% (w) of Lycium barbarum, from about 10% (w) to 15% (w) of Acorus tatarinowii, and from about 10% (w) to 15% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 62.5% (w) of Ophiopogon japonicus, about 12.5% (w) of Lycium barbarum, about 12.5% (w) of Acorus tatarinowii, and about 12.5% (w) of Codonopsis pilosula.

[0095] In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises about 8% (w) to 15% (w) of Ophiopogon japonicus, about 55% (w) to 80% (w) of Lycium barbarum, about 8% (w) to 15% (w) of Acorus tatarinowii, and about 8% (w) to 15% (w) of Codonopsis pilosula. In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises about 10% (w) to 15% (w) of Ophiopogon japonicus, about 55% (w) to 70% (w) of Lycium barbarum, about 10% (w) to 15% (w) of Acorus tatarinowii, and about 10% (w) to 15% (w) of Codonopsis pilosula. In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises about 10% (w) to 20% (w) of Ophiopogon japonicus, about 60% (w) to 70% (w) of Lycium barbarum, about 10% (w) to 20% (w) of Acorus tatarinowii, and about 10% (w) to 20% (w) of Codonopsis pilosula. In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises about 10% (w) to 15% (w) of Ophiopogon japonicus, about 60% (w) to 65% (w) of Lycium barbarum, about 10% (w) to 15% (w) of Acorus tatarinowii, and about 10% (w) to 15% (w) of Codonopsis pilosula. In some embodiments of any of the above traditional Chinese medicine extract compositions, the mixture comprises about 12.5% (w) of Ophiopogon japonicus, about 62.5% (w) of Lycium barbarum, about 12.5% (w) of Acorus tatarinowii, and about 12.5% (w) of Codonopsis pilosula.

[0096] In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 8% (w) to 15% (w) of Ophiopogon japonicus, about 8% (w) to 15% (w) of Lycium barbarum, about 55% (w) to 80% (w) of Acorus tatarinowii, and about 8% (w) to 15% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 10% (w) to 15% (w) of Ophiopogon japonicus, about 10% (w) to 15% (w) of Lycium barbarum, about 55% (w) to 70% (w) of Acorus tatarinowii, and about 10% (w) to 15% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 10% (w) to 20% (w) of Ophiopogon japonicus, about 10% (w) to 20% (w) of Lycium barbarum, about 60% (w) to 70% (w) of Acorus tatarinowii, and about 10% (w) to 20% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 10% (w) to 15% (w) of Ophiopogon japonicus, about 10% (w) to 15% (w) of Lycium barbarum, about 60% (w) to 65% (w) of Acorus tatarinowii, and about 10% (w) to 15% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 12.5% (w) of Ophiopogon japonicus, about 12.5% (w) of Lycium barbarum, about 62.5% (w) of Acorus tatarinowii, and about 12.5% (w) of Codonopsis pilosula.

[0097] In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 8% (w) to 15% (w) of Ophiopogon japonicus, about 8% (w) to 15% (w) of Lycium barbarum, about 8% (w) to 15% (w) of Acorus tatarinowii, and about 55% (w) to 80% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 10% (w) to 15% (w) of Ophiopogon japonicus, about 10% (w) to 15% (w) of Lycium barbarum, about 10% (w) to 15% (w) of Acorus tatarinowii, and about 55% (w) to 70% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 10% (w) to 20% (w) of Ophiopogon japonicus, about 10% (w) to 20% (w) of Lycium barbarum, about 10% (w) to 20% (w) of Acorus tatarinowii, and about 60% (w) to 70% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 10% (w) to 15% (w) of Ophiopogon japonicus, about 10% (w) to 15% (w) of Lycium barbarum, about 10% (w) to 15% (w) of Acorus tatarinowii, and about 60% (w) to 65% (w) of Codonopsis pilosula. In some embodiments of any of the above Chinese herbal extract compositions, the mixture comprises about 12.5% (w) of Ophiopogon japonicus, about 12.5% (w) of Lycium barbarum, about 12.5% (w) of Acorus tatarinowii, and about 62.5% (w) of Codonopsis pilosula.

[0098] In some embodiments of any of the above Chinese medicine extract compositions, the mixture contains about 1 kg to 5 kg of Ophiopogon japonicus, about 1 kg to 5 kg of Lycium barbarum, about 1 kg to 5 kg of Acorus tatarinowii, and about 1 kg to 5 kg of Codonopsis pilosula per 6 kg of the mixture. In some embodiments of any of the above Chinese medicine extract compositions, the mixture contains about 1 kg to 5 kg of Ophiopogon japonicus, about 1 kg to 5 kg of Lycium barbarum, about 1 kg to 5 kg of Acorus tatarinowii, and about 1 kg to 5 kg of Codonopsis pilosula per 8 kg of the mixture. In some embodiments of any of the above Chinese medicine extract compositions, the mixture contains about 1 kg to 5 kg of Ophiopogon japonicus, about 1 kg to 5 kg of Lycium barbarum, about 1 kg to 5 kg of Acorus tatarinowii, and about 1 kg to 5 kg of Codonopsis pilosula per 12 kg of the mixture. In some embodiments of any of the above Chinese medicine extract compositions, the mixture contains about 1 kg to 5 kg of Ophiopogon japonicus, about 1 kg to 5 kg of Lycium barbarum, about 1 kg to 5 kg of Acorus tatarinowii, and about 1 kg to 5 kg of Codonopsis pilosula per 16 kg of the mixture. In some embodiments of any of the above Chinese medicine extract compositions, the mixture contains about 1 kg of Ophiopogon japonicus, about 1 kg of Lycium barbarum, about 1 kg of Acorus tatarinowii, and about 1 kg of Codonopsis pilosula per 4 kg of the mixture. In some embodiments of any of the above Chinese medicine extract compositions, the mixture contains about 5 kg of Ophiopogon japonicus, about 1 kg of Lycium barbarum, about 1 kg of Acorus tatarinowii, and about 1 kg of Codonopsis pilosula per 8 kg of the mixture. In some embodiments of any of the above Chinese medicine extract compositions, the mixture contains about 1 kg of Ophiopogon japonicus, about 5 kg of Lycium barbarum, about 1 kg of Acorus tatarinowii, and about 1 kg of Codonopsis pilosula per 8 kg of the mixture. In some embodiments of any of the above Chinese medicine extract compositions, the mixture contains about 1 kg of Ophiopogon japonicus, about 1 kg of Lycium barbarum, about 5 kg of Acorus tatarinowii, and about 1 kg of Codonopsis pilosula per 8 kg of the mixture. In some embodiments of any of the above Chinese medicine extract compositions, the mixture contains about 1 kg of Ophiopogon japonicus, about 1 kg of Lycium barbarum, about 1 kg of Acorus tatarinowii, and about 5 kg of Codonopsis pilosula per 8 kg of the mixture.

[0099] Traditional Chinese medicine extract composition and preparation method

[0100] Certain aspects of the present application provide a method for preparing a Chinese medicine extract composition from a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, the method comprising: i) adding a liquid to the mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula; ii) heating the mixture in the liquid at a temperature approximately at the boiling point of the liquid for about 30 minutes to about 60 minutes; and iii) collecting a liquid extract from the heated mixture. In some embodiments, the liquid added to the mixture is an aqueous solution. In some embodiments, the liquid added to the mixture is water.

[0101] In some embodiments, a method for preparing a traditional Chinese medicine extract composition from a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula is provided, the method comprising: i) adding water to the mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula; ii) heating the mixture in the water at a temperature of about 100 °C for about 30 minutes to about 60 minutes; and iii) collecting the liquid extract from the heated mixture.

[0102] In some embodiments, the ratio of the weight (w / w) of the added liquid (such as water) to the volume of the traditional Chinese medicine mixture is any one of the following: about 20:1, about 15:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, about 1:15, or about 1:20. In some embodiments, enough liquid (such as water) is added such that the traditional Chinese medicine mixture is completely submerged in the liquid before extraction. In some embodiments, enough liquid is added such that any solid residue remaining in the traditional Chinese medicine mixture after extraction is completely submerged in the liquid. In some embodiments, the following amounts of liquid are added to each 1 kg of the traditional Chinese medicine mixture: about 0.1 L, about 0.2 L, about 0.3 L, about 0.4 L, about 0.5 L, about 0.6 L, about 0.7 L, about 0.8 L, about 0.9 L, about 1 L, about 1.5 L, about 2 L, about 2.5 L, about 3 L, about 4 L, about 5 L, about 6 L, about 7 L, about 8 L, about 9 L, or about 10 L. In some embodiments, the following amounts of liquid are added to each 1 kg of the traditional Chinese medicine mixture: about 0.1 L to 0.25 L, about 0.25 L to 0.5 L, about 0.5 L to 0.75 L, about 0.75 L to 1 L, about 1 L to 2 L, about 2 L to 3 L, about 3 L to 4 L, about 4 L to 5 L, about 5 L to 6 L, about 6 L to 7 L, about 7 L to 8 L, about 8 L to 9 L, or about 9 L to 10 L.

[0103] In some instances, the traditional Chinese medicine mixture can be processed prior to the extraction step. For example, the mixture can be first broken down into smaller pieces and / or boiled, and then heated with a liquid added to improve the extraction efficiency. In some embodiments, the mixture is crushed. In some embodiments, the mixture is ground. In some embodiments, the mixture is cut into smaller slices. The traditional Chinese medicine mixture can be broken down into smaller pieces using any one of a kitchen knife, a pestle and mortar, a kitchen blender, a fine powder grinder, or an industrial grinder. In some embodiments, the method includes grinding the traditional Chinese medicine mixture into a powder. In some embodiments, the method includes grinding the traditional Chinese medicine mixture into particles having an average diameter of about 0.1 mm to 0.2 mm, about 0.2 mm to 0.3 mm, about 0.3 mm to 0.4 mm, about 0.4 mm to 0.5 mm, about 0.5 mm to 0.6 mm, about 0.6 mm to 0.7 mm, about 0.7 mm to 0.8 mm, about 0.8 mm to 0.9 mm, about 0.9 mm to 1.0 mm, about 1 mm to 2 mm, 2 mm to 5 mm, or about 5 mm to 10 mm. In some embodiments, the method includes grinding the traditional Chinese medicine mixture into particles having an average diameter of about 5 μm to 10 μm, about 10 μm to 20 μm, about 20 μm to 30 μm, about 30 μm to 40 μm, about 40 μm to 50 μm, about 50 μm to 60 μm, about 60 μm to 70 μm, about 70 μm to 80 μm, about 80 μm to 90 μm, or about 90 μm to 100 μm.

[0104] Then, an extraction step including heating in a liquid can be performed on the traditional Chinese medicine mixture or the processed traditional Chinese medicine mixture. In some embodiments, the method includes heating the mixture in the liquid at any one of the following temperatures: about 40°C to 50°C, about 50°C to 60°C, about 60°C to 70°C, about 70°C to 80°C, about 80°C to 90°C, about 90°C to 100°C, 100°C to 110°C, about 110°C to 120°C, about 120°C to 130°C, about 130°C to 140°C, about 140°C to 150°C, about 150°C to 160°C, about 160°C to 170°C, about 170°C to 180°C, about 180°C to 190°C, or about 190°C to 200°C. In some embodiments, the method includes heating the mixture in water at any one of the following temperatures: about 60°C to 80°C, about 80°C to 100°C, or about 100°C to 120°C. In some embodiments, the method includes heating the mixture in water at a temperature of about 90°C to 100°C. In some embodiments, the method includes heating the mixture in water at a temperature of about 100°C.

[0105] In some embodiments, the method includes heating a mixture in a liquid at a temperature not exceeding about 150°C. In some embodiments, the method includes heating a mixture in a liquid at a temperature not exceeding any of the following: about 70°C, about 80°C, about 90°C, about 100°C, about 110°C, about 120°C, about 130°C, about 140°C, or about 150°C. In some embodiments, the method includes heating a mixture in water at a temperature not exceeding about 100°C. In some embodiments, the method includes heating a mixture in a liquid at a temperature not exceeding any of the following: about 65°C, about 70°C, about 75°C, about 80°C, about 85°C, about 90°C, about 95°C, or about 100°C.

[0106] In some embodiments, the method includes heating a mixture in a liquid at a temperature not less than about 50°C. In some embodiments, the method includes heating a mixture in a liquid at a temperature not less than any of the following: about 40°C, about 45°C, about 50°C, about 55°C, about 60°C, about 65°C, about 70°C, about 75°C, about 80°C, about 85°C, about 90°C, about 95°C, about 100°C, about 110°C, about 120°C, about 130°C, about 140°C, or about 150°C. In some embodiments, the method includes heating a mixture in water at a temperature not less than about 50°C. In some embodiments, the method includes heating a mixture in water at a temperature not less than any of the following: about 40°C, about 45°C, about 50°C, about 55°C, about 60°C, about 65°C, about 70°C, about 75°C, about 80°C, about 85°C, about 90°C, or about 95°C.

[0107] The traditional Chinese medicine extract can be extracted by heating in a liquid at a temperature slightly below the boiling point of the liquid. Thus, in some embodiments, the method includes heating a mixture in a liquid at a temperature about 1°C to 5°C or about 5°C to 10°C below the boiling point of the liquid. In some embodiments, the method includes heating a mixture in water to about 80% to 99% of the boiling point temperature of the liquid. For example, in some cases, the method includes heating a mixture in water at about 80°C to 99°C when the boiling point of water is 100°C.

[0108] In some embodiments, the boiling point of the liquid is about 80°C to about 200°C. In some embodiments, the boiling point of the liquid is any of the following temperature ranges: about 80°C to 90°C, about 90°C to 100°C, about 100°C to 110°C, about 110°C to 120°C, about 120°C to 130°C, about 130°C to 140°C, about 140°C to 150°C, about 150°C to 160°C, about 160°C to 170°C, about 170°C to 180°C, about 180°C to 190°C, or about 190°C to 200°C.

[0109] Absolute pressure is the zero reference pressure relative to an ideal vacuum and is equal to the sum of the gauge pressure and the atmospheric pressure, where the atmospheric pressure can vary based on geographical location and altitude. Thus, when heating or cooking in a pressure-adjustable device, the absolute pressure is the gauge pressure shown on the device plus the surrounding atmospheric pressure. The absolute pressure during extraction of the traditional Chinese medicine mixture may also affect the spectrum of active ingredients in the traditional Chinese medicine extract composition. Accordingly, in some embodiments, the method includes heating the mixture in the liquid at an absolute pressure that is below, equal to, or above the atmospheric pressure at sea level. In some embodiments, the method includes heating the mixture in the liquid at any of the following absolute pressures: about 50 kPa to 60 kPa, about 60 kPa to 70 kPa, about 70 kPa to 80 kPa, about 80 kPa to 90 kPa, about 90 kPa to 100 kPa, about 100 kPa to 110 kPa, about 110 kPa to 120 kPa, about 120 kPa to 130 kPa, about 130 kPa to 140 kPa, about 140 kPa to 150 kPa, about 150 kPa to 160 kPa, about 160 kPa to 170 kPa, about 170 kPa to 180 kPa, about 180 kPa to 190 kPa, about 190 kPa to 200 kPa, about 200 kPa to 210 kPa, about 210 kPa to 220 kPa, about 220 kPa to 230 kPa, about 230 kPa to 240 kPa, about 240 kPa to 250 kPa, about 250 kPa to 260 kPa, about 260 kPa to 270 kPa, about 270 kPa to 280 kPa, about 280 kPa to 290 kPa, about 290 kPa to 300 kPa, about 300 kPa to 310 kPa, about 310 kPa to 320 kPa, about 320 kPa to 330 kPa, about 330 kPa to 340 kPa, or about 340 kPa to 350 kPa. For example, heating the mixture in a liquid (such as water) in a pressure-adjustable heating device (including but not limited to a pressure cooker).

[0110] The amount of time the Chinese medicine is heated in the liquid can affect the spectrum of active ingredients and can also affect the relative amount of active ingredients extracted. Thus, in some embodiments, the method includes heating the mixture for about 5 minutes to about 10 hours. In some embodiments, the method includes heating the mixture for about 5 minutes to about 24 hours. In some embodiments according to any of the above methods, the method includes heating the mixture for about 5 minutes to 10 minutes, about 10 minutes to 30 minutes, about 30 minutes to 60 minutes, about 1 hour to 2 hours, about 2 hours to 4 hours, about 4 hours to 6 hours, about 6 hours to 8 hours, about 8 hours to 10 hours, about 10 hours to 12 hours, about 12 hours to 14 hours, about 14 hours to 16 hours, about 16 hours to 18 hours, about 18 hours to 20 hours, about 20 hours to 22 hours, or about 22 hours to 24 hours. In some embodiments according to any of the above methods, the method includes heating the mixture for about 1 minute to 5 minutes, about 5 minutes to 10 minutes, about 10 minutes to 20 minutes, about 20 minutes to 30 minutes, about 30 minutes to 40 minutes, about 40 minutes to 50 minutes, about 50 minutes to 60 minutes, about 1 hour to 1.5 hours, about 1.5 hours to 2 hours, about 2 hours to 3 hours, about 3 hours to 4 hours, about 4 hours to 5 hours, about 5 hours to 6 hours, about 6 hours to 7 hours, about 7 hours to 8 hours, about 8 hours to 9 hours, about 9 hours to 10 hours, about 11 hours to 12 hours, about 12 hours to 13 hours, about 13 hours to 14 hours, about 14 hours to 15 hours, about 15 hours to 16 hours, about 16 hours to 17 hours, about 17 hours to 18 hours, about 18 hours to 19 hours, about 19 hours to 20 hours, about 20 hours to 21 hours, about 21 hours to 22 hours, about 22 hours to 23 hours, or about 23 hours to 24 hours. In some embodiments according to any of the above methods, the method includes heating the mixture for any of the following times: about 2 minutes, about 5 minutes, about 10 minutes, about 20 minutes, about 30 minutes, about 40 minutes, about 50 minutes, about 1 hour, about 1.5 hours, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, about 22 hours, about 23 hours, or about 24 hours. In some embodiments, the method includes heating the mixture for at least about 30 minutes (such as any of about 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours or more hours).In some embodiments, additional liquid can be added to the mixture at one or more time points during heating, for example, one or more times during any of the following time periods after the start of heating: about 1 hour, about 1.5 hours, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, about 22 hours, or about 23 hours.

[0111] In some embodiments, the liquid extract is collected before the heated mixture is cooled. In some embodiments, the liquid extract is collected after the heated mixture is cooled. The liquid extract can be collected by physically separating the solid residue. In some embodiments, the liquid extract is collected by decanting from the heated mixture. In some embodiments, the liquid extract is collected by flowing the heated mixture through one or more flow-limiting structures. Many devices include flow-limiting structures suitable for physically separating solid residues, including but not limited to sieves, coarse filters, fine filters, separation membranes, or porous matrices. Thus, in some embodiments, the liquid extract is collected by flowing the heated mixture through one or more sieves, coarse filters, fine filters, separation membranes, or porous matrices. In some embodiments, the diameter of the flow-limiting structure through which the liquid extract flows is about 5 μm, about 10 μm, about 15 μm, about 20 μm, about 25 μm, about 30 μm, about 40 μm, about 50 μm, about 60 μm, about 70 μm, about 80 μm, about 90 μm, about 100 μm, about 150 μm, about 200 μm, about 300 μm, about 400 μm, about 500 μm, about 600 μm, about 700 μm, about 800 μm, about 900 μm, 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, or about 10 mm. In some embodiments, the liquid extract flows through a series of flow-limiting structures with gradually decreasing pore sizes. For example, the heated mixture can flow through a series of coarse filters, starting with a 10 mm coarse filter, then sequentially through a 1 mm coarse filter, a 100 μm coarse filter, and finally through a 10 μm coarse filter, to allow efficient retention of residues of different particle sizes without clogging these coarse filters. In some embodiments, the diameter of the flow-limiting structure used is at least about 1 μm, about 2 μm, about 3 μm, about 4 μm, about 5 μm, about 10 μm, about 20 μm, about 30 μm, about 40 μm, about 50 μm, or about 100 μm smaller than the average diameter of the starting traditional Chinese medicine mixture. Different extraction parameters (such as heating temperature and heating duration) can affect the active ingredient profile. After extraction, the liquid extract can include an extract of the traditional Chinese medicine mixture formulated in water. Thus, in some embodiments, the liquid extract contains about 1% to 5%, about 5% to 10%, about 10% to 15%, about 15% to 20%, about 20% to 25%, about 25% to 30%, about 30% to 35%, about 35% to 40%, about 40% to 45%, about 45% to 50%, about 50% to 55%, about 55% to 60%, about 60% to 65%, about 65% to 70%, about 70% to 75%, about 75% to 80%, about 80% to 85%, about 85% to 90%, about 90% to 95%, or about 95% to 97% water by weight.

[0112] In some embodiments, the method further includes packaging and sealing the traditional Chinese medicine extract composition RM01 in a sterile container. In some embodiments, the container is a bottle.

[0113] The present disclosure further provides a traditional Chinese medicine extract composition prepared by any one of the methods described herein.

[0114] For example, in certain aspects, there is provided a traditional Chinese medicine extract composition comprising an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Angelica pubescens, wherein the traditional Chinese medicine extract composition is prepared by a method comprising the steps of: i) adding water to a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula to obtain a mixture in water; ii) heating the mixture in water at a temperature of about 100 °C for about 30 minutes to about 60 minutes; iii) collecting the liquid extract from the heated mixture. In some embodiments, the traditional Chinese medicine extract composition is prepared by any one of the above methods.

[0115] Pharmaceutical composition

[0116] The above traditional Chinese medicine extract composition RM01 can be provided in a form suitable for oral administration.

[0117] In some embodiments of any one of the traditional Chinese medicine extracts described herein, the traditional Chinese medicine extract composition is further concentrated. In some embodiments, the traditional Chinese medicine extract composition is further concentrated and then dried into a powder. In some embodiments, the traditional Chinese medicine extract composition is further concentrated such that the concentration is increased by any one of the following percentages: 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, 200%, 225%, 250%, 275%, 300%, 350%, 400%, or 500%. In some embodiments, the traditional Chinese medicine extract composition is further concentrated such that the concentration is increased by at least any one of the following multiples: 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 50-fold. In some embodiments, the traditional Chinese medicine extract composition can be air-dried or dried using an incubator, oven, or dryer.

[0118] In some embodiments, the traditional Chinese medicine extract (including but not limited to the further concentrated extract) can be dried into a powder. In some embodiments, the traditional Chinese medicine extract can be dried into a powder and then formulated into capsules according to a formula. In some embodiments, the traditional Chinese medicine extract can be formulated into a tea bag after drying. In some embodiments, the traditional Chinese medicine extract powder can be reconstituted (such as with room temperature water, warm water, or hot water) before administration. In some embodiments, the traditional Chinese medicine extract in the tea bag can be reconstituted by soaking the tea bag in warm water or hot water.

[0119] In some embodiments, a container for holding a traditional Chinese medicine extract composition is provided. In some embodiments, the container is opaque. In some embodiments, the container further includes a label identifying the traditional Chinese medicine extract composition. In some embodiments, the container is a bottle. In some embodiments, the container is sterile. Thus, in some embodiments, a sealed bottle for holding a traditional Chinese medicine extract composition is provided.

[0120] Method for treating diseases

[0121] Kit

[0122] Also provided is a kit or article for treating an individual suffering from a disease (such as Alzheimer's disease). In some embodiments, the kit includes the traditional Chinese medicine extract composition described herein. In some embodiments, the kit includes a traditional Chinese medicine extract composition prepared according to the method described herein. In some embodiments, the kit includes a composition of the traditional Chinese medicine mixture described herein. In some embodiments, the kit includes the composition described herein in a suitable package (e.g., a composition of the traditional Chinese medicine mixture described herein, the traditional Chinese medicine extract composition described herein, or a traditional Chinese medicine extract composition in the form of a patch described herein). Suitable packaging materials are known in the art and include, for example, vials (such as sealed vials), containers, ampoules, bottles, jars, and flexible packaging. These articles can be further sterilized and / or sealed. A method for producing the kit or article is further provided.

[0123] All publicly referenced documents, manuscripts, and scientific literature cited herein are hereby incorporated by reference. Although the present invention has been specifically shown and described with reference to embodiments of the invention, those skilled in the art will understand that various changes in form and detail may be made therein without departing from the scope of the invention as covered by the appended claims.

[0124] Exemplary embodiment

[0125] Embodiment 1. A method for treating a neurodegenerative disease or disorder in an individual, comprising administering to the individual a traditional Chinese medicine extract composition "RM01", the traditional Chinese medicine extract composition comprising an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula.

[0126] Embodiment 2. The method according to Embodiment 1, wherein the mixture comprises about 10% (w) to 70% (w) Ophiopogon japonicus, about 10% (w) to 70% (w) Lycium barbarum, about 10% (w) to 70% (w) Acorus tatarinowii, and about 10% (w) to 70% (w) Codonopsis pilosula.

[0127] Embodiment 3. The method according to Embodiment 1 or Embodiment 2, wherein the mixture comprises about 20% (w) to 30% (w) of Ophiopogon japonicus, about 20% (w) to 30% (w) of Lycium barbarum, about 20% (w) to 30% (w) of Acorus tatarinowii, and about 20% (w) to 30% (w) of Codonopsis pilosula.

[0128] Embodiment 4. The method according to any one of Embodiments 1 to 3, wherein the disease or disorder is Alzheimer's disease (AD).

[0129] Embodiment 5. The method according to Embodiment 4, wherein the individual has mild AD, or has an MMSE score of 20 to 24.

[0130] Embodiment 6. The method according to Embodiment 4, wherein the individual has moderate AD, or has an MMSE score of 13 to 20.

[0131] Embodiment 7. The method according to Embodiment 4, wherein the individual has severe AD, or has an MMSE score of less than 12.

[0132] Embodiment 8. The method according to any one of Embodiments 1 to 3, wherein the individual has mild cognitive impairment (MCI) disease.

[0133] Embodiment 9. The method according to any one of Embodiments 1 to 8, wherein the individual has memory loss.

[0134] Embodiment 10. The method according to any one of Embodiments 1 to 9, wherein the traditional Chinese medicine extract composition RM01 is orally administered to the individual.

[0135] Embodiment 11. The method according to any one of Embodiments 1 to 10, wherein the individual is a human.

[0136] Embodiment 12. A traditional Chinese medicine extract composition "RM01", which comprises an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula.

[0137] Embodiment 13. The traditional Chinese medicine extract composition according to Embodiment 12, wherein the mixture comprises about 10% (w) to 70% (w) of Ophiopogon japonicus, about 10% (w) to 70% (w) of Lycium barbarum, about 10% (w) to 70% (w) of Acorus tatarinowii, and about 10% (w) to 70% (w) of Codonopsis pilosula.

[0138] Embodiment 14. The traditional Chinese medicine extract composition according to Embodiment 12 or 13, wherein the mixture comprises about 20% (w) to 30% (w) of Ophiopogon japonicus, about 20% (w) to 30% (w) of Lycium barbarum var. Pohl, about 20% (w) to 30% (w) of Acorus tatarinowii, and about 20% (w) to 30% (w) of Codonopsis pilosula.

[0139] Embodiment 15. A method for preparing a traditional Chinese medicine extract composition from a mixture comprising Ophiopogon japonicus, Lycium barbarum var. Pohl, Acorus tatarinowii, and Codonopsis pilosula, the method comprising: i) adding a liquid to the mixture comprising Ophiopogon japonicus, Lycium barbarum var. Pohl, Acorus tatarinowii, and Codonopsis pilosula to obtain a mixture in the liquid; ii) heating the mixture in the liquid at a temperature approximately at the boiling point of the liquid for about 30 minutes to about 60 minutes; iii) collecting a liquid extract from the heated mixture; optionally, wherein the liquid is an aqueous solution, and further optionally the liquid is water.

[0140] Embodiment 16. A method for preparing a traditional Chinese medicine extract composition from a mixture comprising Ophiopogon japonicus, Lycium barbarum var. Pohl, Acorus tatarinowii, and Codonopsis pilosula, the method comprising: i) adding water to the mixture comprising Ophiopogon japonicus, Lycium barbarum var. Pohl, Acorus tatarinowii, and Codonopsis pilosula to obtain a mixture in water; ii) heating the mixture in water at a temperature of about 100 °C for about 30 minutes to about 60 minutes; iii) collecting a liquid extract from the heated mixture.

[0141] Embodiment 17. The method according to Embodiment 15 or Embodiment 16, wherein the mixture comprises about 10% (w) to 70% (w) of Ophiopogon japonicus, about 10% (w) to 70% (w) of Lycium barbarum var. Pohl, about 10% (w) to 70% (w) of Acorus tatarinowii, and about 10% (w) to 70% (w) of Codonopsis pilosula.

[0142] Embodiment 18. The method according to any one of Embodiments 15 to 17, wherein the mixture comprises about 20% (w) to 30% (w) of Ophiopogon japonicus, about 20% (w) to 30% (w) of Lycium barbarum var. Pohl, about 20% (w) to 30% (w) of Acorus tatarinowii, and about 20% (w) to 30% (w) of Codonopsis pilosula.

[0143] Embodiment 19. A traditional Chinese medicine extract composition prepared by the method according to any one of Embodiments 15 to 18.

[0144] Embodiment 20. The traditional Chinese medicine extract composition according to any one of Embodiments 12 to 14 and 19, further comprising an excipient.

[0145] Example

[0146] Those skilled in the art will recognize that several embodiments are possible within the scope and spirit of the present invention. The present invention will now be described in more detail with reference to the following non-limiting examples. The following examples further illustrate the present invention, but should of course not be construed as limiting its scope in any way.

[0147] Example 1 Preparation of traditional Chinese medicine extract composition 。

[0148] The following steps were carried out to prepare the herbal extract composition. The quality of Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii and Codonopsis pilosula was inspected according to the quality standards specified in the Chinese Pharmacopoeia. Then, the rhizomes of Acorus tatarinowii and the roots of Codonopsis pilosula were cut into slices about 1 cm thick. Next, about 1 kg each of Ophiopogon japonicus, Lycium barbarum, sliced rhizomes of Acorus tatarinowii and sliced roots of Codonopsis pilosula were decocted in water for 30 to 60 minutes. The liquid part extracted was RM01.

[0149] Example 2 Determination of in vivo efficacy

[0150] To determine the therapeutic efficacy of the traditional Chinese medicine extract composition RM01, the traditional Chinese medicine extract composition formulated in water was tested in an APP / PS1 mouse model.

[0151] The APP / PS1 mice used carried two human transgenes: the APP gene with the Swedish mutation, and the PSE1 gene carrying the L166P mutation. In these mice, the expression of the human APP transgene was about 3 times higher than that of the endogenous mouse APP. Amyloid plaques began to deposit in the neocortex at about six weeks of age and in the hippocampus at about three to four months of age. Amyloid plaque deposition was widely used to test the effects of these drugs on learning and memory performance.

[0152] RM01 was concentrated 4-fold from the original concentration. APP / PS1 transgenic mice were administered RM01 at 6 months of age and their performance was evaluated. The mice were evenly divided into two groups. The mice in Group 1 were orally administered 0.25 ml of the RM01 concentrated solution once a day for two consecutive months. The mice in Group 2 (control group) were treated with physiological saline. Non-transgenic wild-type mice were set as Group 3 (control group) and were also given physiological saline (n = 5 - 10 mice / group).

[0153] The Morris water maze experiment was conducted. The experimental equipment was a circular pool with a diameter of 120 cm, filled with water and equipped with an escape platform with a diameter of 11 cm. Both groups of mice received water maze training: first, they underwent 1 to 2 days of adaptive training on the visible platform, and then they transferred to the hidden platform for 6 to 7 consecutive days of formal training. During the hidden platform training stage, a titanium dioxide (TiO2) suspension was added to the pool to make the water turbid, and the platform was fixed at a depth of 1 cm below the water surface. In all test rounds, the experimental animals entered the water from a randomly selected starting point. On the last day, the underwater platform was removed, and the memory retention ability of the mice was evaluated by tracking their movement trajectories to explore the original platform position within 60 seconds.

[0154] Data were analyzed using Ethovision animal tracking software. By plotting the mean latency curves of the four daily tests for each group of mice during the hidden platform training stage, their spatial learning abilities were compared. On the last day, the memory function of the mice was compared by evaluating their behavioral performance in exploring the platform within the target quadrant. The specific analysis parameters included the exploration time and movement path length in the target quadrant, as Figure 1 shown.

[0155] Example 3 Human efficacy study .

[0156] The patient was a 61-year-old Chinese male with a current medical history of approximately 10 years, which had persisted since the first discovery of memory loss affecting daily life. The patient had been taking memantine and donepezil for a long time to treat his condition. However, both of these medications had been discontinued before the visit. The patient's wife informed that the reason for discontinuation was that the medications had little effect on symptom improvement after long-term use. On the contrary, the patient gradually declined in memory, cognition, and daily function.

[0157] The patient underwent a Mini-Mental State Examination (MMSE) assessment at the first visit. The patient had lost time orientation, had short-term memory loss, was unable to repeat the examiner's statements, had lost calculation ability, and was unable to follow instructions. The MMSE score was 5, indicating that the patient suffered from severe Alzheimer's disease.

[0158] The patient received treatment with the traditional Chinese medicine extract composition RM01, twice a day for five weeks. The family members assisted in completing all treatment processes throughout.

[0159] One week after treatment, the patient's MMSE was re-evaluated. At the same time, the family members were asked in detail about the patient's daily life, including sleep, mood, interpersonal response, behavior, and mental symptoms.

[0160] Treatment and re-evaluation continued for 5 weeks. The MMSE scores are shown in Figure 2 , indicating that the patient's symptoms had improved significantly. The family members reported an improvement in the patient's daily living ability.

[0161] Example 4

[0162] RM01 was administered to APP / PS1 mice to evaluate the effect of RM01 on reducing β-amyloid plaques. A total of three groups of four mice each were set up in the experiment: APP / PS1 mice were given saline by gavage as the disease control group; APP / PS1 mice were given RM01 orally; C57 wild-type mice were also given RM01 orally as the normal control group. Mice were given 0.8 ml of RM01 orally every day, and the control group was given saline. After two months of treatment, the mice were euthanized and immunohistochemical tests were performed on β-amyloid plaques. Two brain sections of each mouse were evaluated, and the total number of β-amyloid plaques was counted and the average value was calculated. See Figure 3 and Table 1.

[0163] No amyloid plaques were detected in the control group of C57 wild-type mice, indicating that there was no artificial plaque formation caused by incorrect data. Compared with the APP / PS1 control group mice treated with saline, the number of amyloid plaques in the APP / PS1 group mice administered RM01 was significantly reduced.

[0164] Table 1 .

[0165] Mouse 1 Mouse 2 Mouse 3 Mouse 4 Average APP / PS1 - saline 53 / 54 60 / 87 77 / 67 91 / 138 78 APP / PS1 - RM01 34 / 50 30 / 27 51 / 62 52 / 41 43 C57(WT) 0 / 0 0 / 0 0 / 0 0 / 0 0

Claims

1. A method for treating a neurodegenerative disease or disorder in an individual, comprising administering to the individual a traditional Chinese medicine extract composition "RM01", the traditional Chinese medicine extract composition comprising an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula.

2. The method according to claim 1, wherein the mixture comprises from about 10% (w) to 70% (w) of Ophiopogon japonicus, from about 10% (w) to 70% (w) of Lycium barbarum, from about 10% (w) to 70% (w) of Acorus tatarinowii, and from about 10% (w) to 70% (w) of Codonopsis pilosula.

3. The method according to claim 1 or claim 2, wherein the mixture comprises from about 20% (w) to 30% (w) of Ophiopogon japonicus, from about 20% (w) to 30% (w) of Lycium barbarum, from about 20% (w) to 30% (w) of Acorus tatarinowii, and from about 20% (w) to 30% (w) of Codonopsis pilosula.

4. The method according to any one of claims 1 to 3, wherein the disease or disorder is Alzheimer's disease (AD).

5. The method according to claim 4, wherein the individual has mild AD, or has an MMSE score of 20 to 24.

6. The method according to claim 4, wherein the individual has moderate AD, or has an MMSE score of 13 to 20.

7. The method according to claim 4, wherein the individual has severe AD, or has an MMSE score of less than 12.

8. The method according to any one of claims 1 to 3, wherein the individual has mild cognitive impairment (MCI) disease.

9. The method according to any one of claims 1 to 8, wherein the individual has memory loss.

10. The method according to any one of claims 1 to 9, wherein the traditional Chinese medicine extract composition RM01 is orally administered to the individual.

11. The method according to any one of claims 1 to 10, wherein the individual is a human.

12. A traditional Chinese medicine extract composition "RM01", comprising an extract of a mixture containing Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula.

13. The traditional Chinese medicine extract composition according to claim 12, wherein the mixture comprises from about 10% (w) to 70% (w) of Ophiopogon japonicus, from about 10% (w) to 70% (w) of Lycium barbarum, from about 10% (w) to 70% (w) of Acorus tatarinowii, and from about 10% (w) to 70% (w) of Codonopsis pilosula.

14. The traditional Chinese medicine extract composition according to claim 12 or 13, wherein the mixture comprises about 20% (w) to 30% (w) of Ophiopogon japonicus, about 20% (w) to 30% (w) of Lycium barbarum, about 20% (w) to 30% (w) of Acorus tatarinowii, and about 20% (w) to 30% (w) of Codonopsis pilosula.

15. A method for preparing a traditional Chinese medicine extract composition from a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, the method comprising: i) Add a liquid to the mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula to obtain the mixture in the liquid; ii) Heat the mixture in the liquid at a temperature of about the boiling point of the liquid for about 30 minutes to about 60 minutes; iii) Collect the liquid extract from the heated mixture; Optionally, wherein the liquid is an aqueous solution, and further optionally the liquid is water.

16. A method for preparing a traditional Chinese medicine extract composition from a mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, the method comprising: i) Add water to the mixture comprising Ophiopogon japonicus, Lycium barbarum, Acorus tatarinowii, and Codonopsis pilosula, to obtain the mixture in water; ii) Heat the mixture in water at a temperature of about 100 °C for about 30 minutes to about 60 minutes; iii) Collect the liquid extract from the heated mixture.

17. The method according to claim 15 or claim 16, wherein the mixture comprises about 10% (w) to 70% (w) of Ophiopogon japonicus, about 10% (w) to 70% (w) of Lycium barbarum, about 10% (w) to 70% (w) of Acorus tatarinowii, and about 10% (w) to 70% (w) of Codonopsis pilosula.

18. The method according to any one of claims 15 to 17, wherein the mixture comprises about 20% (w) to 30% (w) of Ophiopogon japonicus, about 20% (w) to 30% (w) of Lycium barbarum, about 20% (w) to 30% (w) of Acorus tatarinowii, and about 20% (w) to 30% (w) of Codonopsis pilosula.

19. A traditional Chinese medicine extract composition prepared by the method according to any one of claims 15 to 18.

20. The traditional Chinese medicine extract composition according to any one of claims 12 to 14 and 19, further comprising an excipient.

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