A traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy, its preparation and application

Abstract

The present invention provides a traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy, its preparation and application. The traditional Chinese medicine composition of the present invention comprises traditional Chinese medicines in the following weight ratios: 15-25 parts of Angelica sinensis, 10-20 parts of Paeonia lactiflora, 8-12 parts of Cinnamomum cassia, 4-6 parts of Asarum sieboldii, 8-12 parts of Glycyrrhiza uralensis, 4-6 parts of Tetrapanax papyriferus, 15-25 parts of Spatholobus suberectus, 25-35 parts of Astragalus membranaceus, 8-12 parts of Liquidambar formosana, 10-20 parts of Codonopsis pilosula, 8-12 parts of Chaenomeles sinensis, 8-12 parts of processed Aconitum carmichaelii, and 25-35 parts of Ziziphus jujuba. In the formula, Angelica sinensis is sweet and warm, nourishing blood and regulating blood; Cinnamomum cassia is pungent and warm, warming the meridians to dispel cold and warming and dredging blood vessels, serving as the monarch drug. Processed Aconitum carmichaelii and Asarum sieboldii warm the meridians to dispel cold, assisting Cinnamomum cassia in warming and dredging blood vessels so that yang qi reaches the four extremities; Paeonia lactiflora nourishes blood and regulates nutrient qi, assisting Angelica sinensis in tonifying nutrient blood, and Astragalus membranaceus and Codonopsis pilosula strengthen the spleen and replenish qi, assisting Angelica sinensis in replenishing qi and generating blood, all serving as the ministerial drugs. Tetrapanax papyriferus dredges the meridians to promote blood circulation, and Spatholobus suberectus, Liquidambar formosana and Chaenomeles sinensis strengthen promoting blood circulation and dredging collaterals; Ziziphus jujuba and Glycyrrhiza uralensis replenish qi, strengthen the spleen and nourish blood, all serving as the adjuvant drugs. Treating chemotherapy-induced peripheral neuropathy with the traditional Chinese medicine formula of the present invention has good clinical curative effects.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy, its preparation and application. Background Art

[0002] Chemotherapy, as one of the common methods for treating malignant tumors, chemotherapy-induced peripheral neuropathy is a common side effect, which is the damage to the peripheral nerve function caused by chemotherapy drugs or their metabolites. A series of symptoms and signs of nerve function disorders are related to the type of chemotherapy drugs, the cumulative chemotherapy dose, and personal factors. In recent years, with the continuous increase in the number of cancer patients and patients who need chemotherapy due to cancer, the side effects of chemotherapy have attracted much attention. Especially chemotherapy-induced peripheral neuropathy (CIPN) not only seriously affects the quality of life of patients, but also becomes the direct reason for dose limitation or discontinuation of some drugs, resulting in poor tumor control. Common clinical manifestations of CIPN patients: Chemotherapy drugs can affect the nervous system of patients, leading to nervous system toxicity. This is mainly because chemotherapy drugs damage the peripheral nerves, and symptoms such as slow reaction, numbness in hands and feet, muscle weakness, fatigue, hearing loss, dizziness, listlessness, constipation or heartburn may occur. Traditional Chinese medicine believes that cancer patients themselves have insufficient vital qi. Chemotherapy drugs are toxic substances that damage the vital qi. After chemotherapy drugs enter the body, they will further damage the vital qi of the body, resulting in insufficient qi and blood, weak nutrient qi and defensive qi. Deficiency of qi leads to weak propulsion and sluggish blood circulation, and deficiency of blood leads to insufficient nourishment. Eventually, the meridians are blocked, the tendons and vessels lose nourishment, and symptoms such as pain and numbness in the extremities occur. Therefore, it is urgent to develop a traditional Chinese medicine formula to effectively treat chemotherapy-induced peripheral neuropathy. Summary of the Invention

[0003] In view of this, the present invention provides a traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy, its preparation and application, so as to solve the above technical problems.

[0004] The technical solution of the present invention is realized as follows:

[0005] A traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy, comprising the following traditional Chinese medicines in parts by weight: 15 - 25 parts of Angelica sinensis, 10 - 20 parts of Paeonia lactiflora, 8 - 12 parts of Cinnamomum cassia, 4 - 6 parts of Asarum heterotropoides, 8 - 12 parts of Glycyrrhiza uralensis, 4 - 6 parts of Tetrapanax papyriferus, 15 - 25 parts of Spatholobus suberectus, 25 - 35 parts of Astragalus membranaceus, 8 - 12 parts of Clerodendrum cyrtophyllum, 10 - 20 parts of Codonopsis pilosula, 8 - 12 parts of Chaenomeles sinensis, 8 - 12 parts of Radix Aconiti Lateralis Preparata, 25 - 35 parts of Ziziphus jujuba.

[0006] A further technical solution is that the traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy comprises traditional Chinese medicines in the following weight ratios: 19-21 parts of Angelica sinensis, 14-16 parts of Paeonia lactiflora, 9-11 parts of Cinnamomum cassia, 4-6 parts of Asarum sieboldii, 9-11 parts of Glycyrrhiza uralensis, 4-6 parts of Tetrapanax papyriferus, 19-21 parts of Spatholobus suberectus, 29-31 parts of Astragalus membranaceus, 9-11 parts of Liquidambar formosana, 14-16 parts of Codonopsis pilosula, 9-11 parts of Chaenomeles sinensis, 9-11 parts of Radix Aconiti Lateralis Preparata, and 29-31 parts of Ziziphus jujuba.

[0007] A further technical solution is that the traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy comprises traditional Chinese medicines in the following weight ratios: 20 parts of Angelica sinensis, 15 parts of Paeonia lactiflora, 10 parts of Cinnamomum cassia, 5 parts of Asarum sieboldii, 10 parts of Glycyrrhiza uralensis, 5 parts of Tetrapanax papyriferus, 20 parts of Spatholobus suberectus, 30 parts of Astragalus membranaceus, 10 parts of Liquidambar formosana, 15 parts of Codonopsis pilosula, 10 parts of Chaenomeles sinensis, 10 parts of Radix Aconiti Lateralis Preparata, and 30 parts of Ziziphus jujuba.

[0008] A traditional Chinese medicine preparation for treating chemotherapy-induced peripheral neuropathy is prepared from the traditional Chinese medicine composition of the present invention.

[0009] A further technical solution is that the preparation is a decoction.

[0010] The traditional Chinese medicine composition of the present invention is used in the preparation of a drug for treating chemotherapy-induced peripheral neuropathy.

[0011] Compared with the prior art, the beneficial effects of the present invention are:

[0012] Peripheral neuropathy belongs to the category of "vascular obstruction due to cold pathogen" in traditional Chinese medicine. In the early stage of this disease, it is mainly caused by deficiency of vital qi, invasion of the six exogenous pathogens, which attack the blood vessels, resulting in blood stasis, obstruction of the blood vessels, and presenting symptoms such as limb pain, numbness of the skin, dark or pale skin color, weak or absent pulse, etc. Most chemotherapy drugs are bitter and cold, which are likely to consume the yang qi of the human body, leading to deficiency of yang qi in tumor patients after chemotherapy, internal generation of yin cold, and at the same time, the spleen yang fails to rise, resulting in insufficient production of qi and blood, deficiency of nutrient blood, and the four extremities not being nourished. In addition, the cold pathogen invades and condenses the meridians when the body is weak, causing unfavorable blood circulation in the blood vessels. Pain occurs due to obstruction and due to lack of nourishment, which is what is called deficiency of blood causing the blood vessels to be insufficient and cold coagulation causing blood stasis. In this formula, Angelica sinensis is sweet and warm, nourishing blood and regulating blood; Cinnamon twig is pungent and warm, warming the meridians to dispel cold and promoting blood circulation in the vessels, serving as the monarch drug. Prepared Aconite root and Asarum dispel cold by warming the meridians, assisting Cinnamon twig to promote blood circulation in the vessels and enabling yang qi to reach the four extremities; White Peony nourishes the nutrient qi and promotes blood circulation, assisting Angelica sinensis in nourishing nutrient blood, Astragalus membranaceus and Codonopsis pilosula invigorate the spleen and replenish qi, assisting Angelica sinensis in replenishing qi and generating blood, all serving as ministerial drugs. Tetrapanax papyriferus promotes blood circulation in the meridians to smooth the blood flow, and Caulis Spatholobi, Clerodendrum trichotomum Thunb. and Chaenomeles sinensis strengthen promoting blood circulation and dredging collaterals; Jujube and Licorice replenish qi, strengthen the spleen and nourish blood, all serving as assistant drugs. The heavy use of jujube not only combines with Angelica sinensis and White Peony to nourish nutrient blood, but also prevents the excessive dryness and harshness of Prepared Aconite root, Cinnamon twig and Asarum from damaging yin blood; Licorice also regulates the properties of the drugs and serves as the guiding drug. The combination of these drugs can effectively treat chemotherapy-induced peripheral neuropathy with remarkable curative effects. Clinically, using the traditional Chinese medicine formula of the present invention to treat chemotherapy-induced peripheral neuropathy, the cure rate is over 76%, and the total effective rate is over 96%, showing good clinical effects and being safe without adverse reactions. Detailed implementation manners

[0013] To better understand the technical content of the present invention, specific examples are provided below to further illustrate the present invention.

[0014] Unless otherwise specified, the experimental methods used in the embodiments of the present invention are all conventional methods.

[0015] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can all be obtained from commercial channels.

[0016] Example 1 - Traditional Chinese medicine formula

[0017] A traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy: prepared from the following raw Chinese medicinal materials by weight: 20 g of Angelica sinensis, 15 g of White Peony, 10 g of Cinnamon twig, 5 g of Asarum, 10 g of Licorice, 5 g of Tetrapanax papyriferus, 20 g of Caulis Spatholobi, 30 g of Astragalus membranaceus, 15 g of Codonopsis pilosula, 10 g of Chaenomeles sinensis, 10 g of Clerodendrum trichotomum Thunb., 10 g of prepared Aconite root, and 30 g of jujube.

[0018] Example 2 - Traditional Chinese medicine formula

[0019] A traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy: It is prepared from the following Chinese medicinal materials by weight: 20 g of Angelica sinensis, 20 g of Paeonia lactiflora, 10 g of Cinnamomum cassia, 10 g of Asarum heterotropoides, 10 g of Glycyrrhiza uralensis, 5 g of Tetrapanax papyriferus, 25 g of Spatholobus suberectus, 25 g of Astragalus membranaceus, 10 g of Codonopsis pilosula, 10 g of Chaenomeles sinensis, 10 g of Liquidambar formosana, 10 g of Aconitum carmichaelii preparata, 25 g of Ziziphus jujuba.

[0020] Comparative Example 1

[0021] The main difference between this control example and Example 1 lies in: not containing Spatholobus suberectus, Astragalus membranaceus, Codonopsis pilosula, Chaenomeles sinensis, Liquidambar formosana, Aconitum carmichaelii preparata, and increasing the dosage of other medicinal flavors.

[0022] A traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy: It is prepared from the following Chinese medicinal materials by weight: 40 g of Angelica sinensis, 35 g of Paeonia lactiflora, 20 g of Cinnamomum cassia, 15 g of Asarum heterotropoides, 30 g of Glycyrrhiza uralensis, 20 g of Tetrapanax papyriferus, 30 g of Ziziphus jujuba.

[0023] Comparative Example 2

[0024] The main difference between this control example and Example 1 lies in: not containing Astragalus membranaceus and Liquidambar formosana, increasing the dosage of Paeonia lactiflora and Codonopsis pilosula, and at the same time increasing the dosage of Spatholobus suberectus and Chaenomeles sinensis.

[0025] A traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy: It is prepared from the following Chinese medicinal materials by weight: 20 g of Angelica sinensis, 30 g of Paeonia lactiflora, 10 g of Cinnamomum cassia, 5 g of Asarum heterotropoides, 10 g of Glycyrrhiza uralensis, 5 g of Tetrapanax papyriferus, 25 g of Spatholobus suberectus, 30 g of Codonopsis pilosula, 15 g of Chaenomeles sinensis, 10 g of Aconitum carmichaelii preparata, 30 g of Ziziphus jujuba.

[0026] According to the traditional Chinese medicine formulas of Examples 1-2 and Control Examples 1-2 respectively, traditional water decoction method was used to prepare traditional Chinese medicine decoctions.

[0027] Example 3 - Clinical Research

[0028] (I) Basic Information

[0029] 120 patients with chemotherapy-induced peripheral neuropathy (CIPN) were collected, aged 18 - 80 years old. They were randomly divided into 4 groups, Study Groups 1 - 4. There were no significant differences among the patients in each group in terms of age, gender, lesion type, disease course, traditional Chinese medicine syndrome type, etc.

[0030] (II) Clinical Manifestations

[0031] CIPN is divided into types such as sensory neuropathy, small fiber neuropathy, motor neuropathy, and autonomic neuropathy. Its main clinical manifestations are shown in Table 1.

[0032] Table 1 Main Lesion Types and Typical Clinical Manifestations of CIPN

[0033]

[0034]

[0035] (III) Clinical Diagnosis and Clinical Evaluation

[0036] Combined with the background of chemotherapy drug application and typical clinical manifestations, CIPN is diagnosed. Differential diagnosis and exclusion of diseases: paraneoplastic syndrome related to tumors, neuropathic pain caused by tumor compression, chronic inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome, multiple sclerosis, etc.), diabetic CIPN, etc.

[0037] The EORTC-QLQ-CIPN20 scoring scale is one of the most commonly used scales for CIPN at present. Tools such as the EORTC-QLQ-CIPN20 scoring scale are used for clinical evaluation.

[0038] (IV) Treatment Methods

[0039] The research groups 1-4 were respectively given the decoctions prepared from the traditional Chinese medicine formulas of Example 1, Example 2, Control Example 1, and Control Example 2, 1 dose per day, decocted in water for oral administration, taken warm in two divided doses, 7 days as a course of treatment, and taken for 1-3 courses of treatment.

[0040] (V) Clinical Efficacy Judgment Criteria

[0041] (1) Clinical cure: Clinical symptoms are significantly relieved or basically disappeared, and the score after treatment is reduced by ≥95% compared with that before treatment.

[0042] (2) Marked effect: Clinical symptoms are significantly improved compared with those before treatment, and 70% ≤ the score after treatment is reduced by <95% compared with that before treatment.

[0043] (3) Effective: Clinical symptoms are improved to some extent, and 30% ≤ the score after treatment is reduced by <70% compared with that before treatment.

[0044] (4) Ineffective: The condition remains unchanged or even worsens.

[0045] The total effective rate = (total effective cases / total cases) × 100%, where the total effective cases = cured cases + markedly effective cases + effective cases.

[0046] (VI) Clinical Efficacy

[0047] Table 2 Clinical Efficacy of Treating CIPN

[0048]

[0049] The results in Table 2 above show that the traditional Chinese medicine formulas of Examples 1-2 of the present invention have good clinical efficacy in treating chemotherapy-induced peripheral neuropathy and are safe without adverse reactions.

[0050] Among them, Control Example 1 does not contain Caulis Spatholobi, Radix Astragali, Radix Codonopsis, Fructus Chaenomelis, Fructus Liquidambaris, Radix Aconiti Lateralis Preparata, and increases the dosages of other medicinal flavors. The clinical cure rate decreases significantly, and the total effective rate also decreases significantly.

[0051] Control Example 2 does not contain Radix Astragali and Fructus Liquidambaris, increases the dosages of Radix Paeoniae Alba and Radix Codonopsis, and at the same time increases the dosages of Caulis Spatholobi and Fructus Chaenomelis. The clinical cure rate also decreases significantly, and the total effective rate also decreases to some extent.

[0052] Example 4 - Clinical Application

[0053] A certain Mr. Feng, male, 78 years old, was initially diagnosed on February 22, 2021. Chief complaint: Numbness at the extremities of the four limbs for 1 week, aggravated for 2 days. The patient was diagnosed with malignant tumor of the palate in December 2019 and underwent resection. The tumor recurred in January 2021. Due to the fact that the neck mass surrounded the carotid artery and jugular vein and the surgical risk was high, after refusing surgical treatment, docetaxel 120 mg + cisplatin 110 mg chemotherapy was performed on February 15, 2021. After chemotherapy, the patient developed numbness and weakness at the extremities of the four limbs without obvious cause, which was not taken seriously and no special treatment was given. The above symptoms aggravated 2 days ago, especially in the upper limbs. In order to seek treatment, the patient came to see a doctor. The current symptoms are as follows: mental fatigue, weakness, numbness at the extremities of the four limbs, like the feeling of ants crawling, aversion to cold, normal defecation and urination. The tongue is pale with white coating, and the pulse is thready and unsmooth. Physical examination: A mass about 3x3 cm in size can be seen in the left neck, with a little bleeding and exudation. The muscle tone and muscle strength of the four limbs are normal, and the tactile sensation at the extremities of the four limbs is weakened. Combining the patient's medical history and related treatments, the western medicine diagnosis is considered: 1. Chemotherapy-induced peripheral neuropathy (CIPN) 2. Recurrence after chemotherapy for postoperative malignant tumor of the palate; The traditional Chinese medicine diagnosis is: syndrome of obstruction of vessels due to deficiency of blood and cold coagulation of meridians. The patient was given the traditional Chinese medicine in Example 1, 7 doses, 1 dose per day, decocted in water and taken warm in two divided doses. And the patient was instructed not to eat cold foods and pay attention to keeping warm.

[0054] On the second diagnosis on February 23, 2021, the patient reported that the numbness at the extremities of the four limbs had been alleviated to some extent after taking the medicine, and the aversion to cold had improved significantly, and the rest was the same as before. The tongue was pale with white coating, and the pulse was thready and unsmooth. The previous prescription was continued to be taken warm for 7 doses, and the decocting and taking methods were the same as before. After 7 doses, the patient reported that the clinical symptoms such as numbness at the extremities of the four limbs had basically disappeared.

[0055] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy, characterized in that, It is made from traditional Chinese medicines in the following weight ratios: 15 - 25 parts of Angelica sinensis, 10 - 20 parts of Paeonia lactiflora, 8 - 12 parts of Cinnamomum cassia, 4 - 6 parts of Asarum sieboldii, 8 - 12 parts of Glycyrrhiza uralensis, 4 - 6 parts of Tetrapanax papyriferus, 15 - 25 parts of Spatholobus suberectus, 25 - 35 parts of Astragalus membranaceus, 8 - 12 parts of Liquidambar formosana, 10 - 20 parts of Codonopsis pilosula, 8 - 12 parts of Chaenomeles sinensis, 8 - 12 parts of processed Aconitum carmichaelii, 25 - 35 parts of Ziziphus jujuba.

2. The traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy according to claim 1, wherein, It is made from traditional Chinese medicines in the following weight ratios: 19 - 21 parts of Angelica sinensis, 14 - 16 parts of Paeonia lactiflora, 9 - 11 parts of Cinnamomum cassia, 4 - 6 parts of Asarum sieboldii, 9 - 11 parts of Glycyrrhiza uralensis, 4 - 6 parts of Tetrapanax papyriferus, 19 - 21 parts of Spatholobus suberectus, 29 - 31 parts of Astragalus membranaceus, 9 - 11 parts of Liquidambar formosana, 14 - 16 parts of Codonopsis pilosula, 9 - 11 parts of Chaenomeles sinensis, 9 - 11 parts of processed Aconitum carmichaelii, 29 - 31 parts of Ziziphus jujuba.

3. The traditional Chinese medicine composition for treating chemotherapy-induced peripheral neuropathy according to claim 1, wherein It is made from traditional Chinese medicines in the following weight ratios: 20 parts of Angelica sinensis, 15 parts of Paeonia lactiflora, 10 parts of Cinnamomum cassia, 5 parts of Asarum sieboldii, 10 parts of Glycyrrhiza uralensis, 5 parts of Tetrapanax papyriferus, 20 parts of Spatholobus suberectus, 30 parts of Astragalus membranaceus, 10 parts of Liquidambar formosana, 15 parts of Codonopsis pilosula, 10 parts of Chaenomeles sinensis, 10 parts of processed Aconitum carmichaelii, 30 parts of Ziziphus jujuba.

4. A traditional Chinese medicine preparation for treating chemotherapy-induced peripheral neuropathy, characterized in that, It is prepared from the traditional Chinese medicine composition according to any one of claims 1 - 3.

5. The traditional Chinese medicine preparation according to claim 4, characterized in that, The preparation is a decoction.

6. The traditional Chinese medicine composition according to any one of claims 1 - 3 is used in the preparation of a drug for treating chemotherapy - induced peripheral neuropathy.

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