A traditional Chinese medicine composition for invigorating spleen and reducing phlegm, delaying liver cancer progression, a traditional Chinese medicine preparation and a preparation method and application thereof

Abstract

The application discloses a traditional Chinese medicine composition, a traditional Chinese medicine preparation and a preparation method and application thereof. The traditional Chinese medicine composition comprises the following components in mass parts: 12-18 parts of Astragalus membranaceus; 12-18 parts of Polygonatum; 12-18 parts of Polygoni Multiflori Radix; 15-21 parts of Semen Perillae; 12-18 parts of Semen Raphani; 12-18 parts of Fritillariae Thunbergii Bulbus; 27-33 parts of Herba Dispori; 7-13 parts of Herba Scutellariae; and 3-9 parts of Radix Glycyrrhizae. The traditional Chinese medicine composition is an oral medicine, the medicine is convenient to prepare, and the medicine experiment on a liver cancer rat model shows that the medicine can effectively relieve the progress of liver cancer, especially can greatly reduce the side effects of the medicine on patients during treatment of liver cancer. The medicine is applied to treatment of liver cancer in clinic, and has remarkable curative effect.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine composition, a traditional Chinese medicine preparation, its preparation method, and its application. Background Technology

[0002] The development of hepatocellular carcinoma (HCC) is a complex process involving multiple risk factors. Chronic hepatitis B virus infection and aflatoxin B1 are major risk factors in developing regions such as China and India. In developed regions, HCC mainly develops from cirrhosis caused by hepatitis C virus and non-alcoholic fatty liver disease. Common treatments for early-stage HCC include liver transplantation, liver resection, and targeted therapy. Although liver resection is the ideal treatment for HCC, it is only suitable for young patients in relatively good physical condition. Even after surgical resection, the recurrence rate remains as high as 70%. Currently, sorafenib and lenvatinib are commonly used clinically to treat HCC, but they only prolong survival by a few months. Due to its insidious and refractory nature, HCC has become one of the most common life-threatening cancers. Summary of the Invention

[0003] The technical problem this invention aims to solve is to overcome the shortcomings of existing drugs for treating hepatocellular carcinoma (HCC) where the efficacy needs improvement, and to provide a traditional Chinese medicine composition, a traditional Chinese medicine preparation, its preparation method, and its application. The traditional Chinese medicine composition of this invention can effectively alleviate the progression of HCC.

[0004] The present invention solves the above-mentioned technical problems through the following technical solution:

[0005] A traditional Chinese medicine composition, by weight parts, comprises the following components:

[0006]

[0007]

[0008] In this invention, preferably, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0009]

[0010] In this invention, more preferably, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0011]

[0012] In a preferred embodiment of the present invention, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0013]

[0014]

[0015] In this invention, there are no special requirements for the source, variety, or form of each component in the raw materials; any commercially available raw material can be used.

[0016] The present invention also provides a method for preparing a traditional Chinese medicine preparation, which includes the following steps: preparing the preparation by using the traditional Chinese medicine composition as described above as raw material to obtain the traditional Chinese medicine preparation.

[0017] In this invention, the dosage form of the traditional Chinese medicine preparation can be any dosage form, such as granules, decoctions, or ointments.

[0018] In this invention, preferably, the preparation method of the traditional Chinese medicine preparation includes the following steps: soaking and decocting the traditional Chinese medicine composition, and collecting the decocted liquid.

[0019] The soaking operation can be a conventional soaking operation in the art. The solvent used for soaking can be a solvent commonly used for soaking traditional Chinese medicine, such as water.

[0020] The soaking temperature is preferably below 40°C, for example, by using conventional cool or warm water.

[0021] The soaking time is preferably 30-60 minutes.

[0022] The solvent used in the decoction is generally the liquid or water obtained after soaking.

[0023] During the decoction process, the amount of solvent used is generally 3-5 cm above the surface of the herbal composition.

[0024] The number of times the decoction is prepared is preferably twice.

[0025] The simmering process preferably includes the following steps: bringing the water to a boil over high heat, then simmering over low heat.

[0026] When the boiling is performed twice:

[0027] The second frying time should ideally be shorter than the first frying time.

[0028] Preferably, the first simmering time is 30-50 minutes, and the second simmering time is 15 minutes.

[0029] Preferably, the preparation method further includes the following step: mixing the medicinal liquids obtained from two decoctions to obtain a mixed medicinal liquid.

[0030] In this invention, preferably, after the decoction, the following steps are further included: filtering, concentrating, and granulating the medicinal liquid.

[0031] The concentration can be achieved by decoction concentration or by a traditional Chinese medicine concentration machine.

[0032] The granulation operation can be performed using conventional granulation methods in the art.

[0033] The administration method of the traditional Chinese medicine preparation of the present invention is generally as follows: oral administration. Adult dosage: taking decoction as an example, the traditional Chinese medicine composition is decocted to 400-600 ml and divided into two doses in the morning and evening, taken half an hour after meals.

[0034] The present invention also provides a traditional Chinese medicine preparation, which is prepared by the method for preparing traditional Chinese medicine preparations as described above.

[0035] In this invention, the dosage form of the traditional Chinese medicine preparation can be any dosage form, such as granules, decoctions, or ointments.

[0036] In this invention, the traditional Chinese medicine preparation may also include excipients.

[0037] The excipients may be conventional excipients used in pharmaceuticals.

[0038] The present invention also provides the use of the traditional Chinese medicine composition or preparation as described above in the preparation of drugs or health products for "treating or preventing liver disease" or "strengthening the spleen and resolving phlegm".

[0039] In this invention, preferably, the liver disease includes liver cancer.

[0040] This invention's herbal composition follows the treatment principle of "strengthening the spleen and resolving phlegm, supporting the body's resistance and inhibiting cancer," prioritizing the strengthening of the body's resistance while supplementing it with the elimination of pathogenic factors, addressing both the root cause and the symptoms. Based on the strengthening of the body's resistance, it also resolves turbidity, lowers lipids, detoxifies, and disperses nodules. While adhering to the ancient wisdom of traditional formulas, it incorporates modern physiology, upholding tradition while innovating, focusing on strengthening the spleen and stomach to resolve phlegm. Based on years of clinical experience, the inventors use Astragalus membranaceus as the chief ingredient, its sweet and warm properties tonifying qi and strengthening the spleen. The Sanzi Yangqin Decoction (Perilla Seed, White Mustard Seed, and Radish Seed) acts as the assistant ingredient, harmonizing the stomach and resolving phlegm. These four ingredients work together to strengthen the spleen and resolve phlegm. Polygonatum sibiricum, Polygonum multiflorum, Scutellaria barbata, and Gecko are used as adjuvant ingredients; the former two tonify the kidneys and clear the bowels, resolving turbidity and lowering lipids, while the latter two detoxify, disperse nodules, and clear residual pathogenic factors. Licorice root acts as the guiding ingredient, protecting the middle jiao and harmonizing the other ingredients. Each component is indispensable; through the synergistic effect of these components, the invention effectively alleviates HCC with low toxicity and side effects.

[0041] The positive and progressive effects of this invention are as follows: The inventors, having absorbed the essence of traditional Chinese medicine and through dedicated research on HCC, especially drug combinations for treating HCC, have invented a traditional Chinese medicine composition. This composition is a spleen-strengthening and phlegm-resolving formula that can effectively alleviate the symptoms of HCC. Drug experiments using a rat model of liver cancer have shown that it can effectively slow the progression of HCC, and significantly reduces the toxic side effects on patients while treating HCC. Clinically, its application in the treatment of HCC has yielded significant therapeutic effects. Attached Figure Description

[0042] Figure 1A The graph shows the change in body weight of rats with primary liver cancer in each group over a period of time each week.

[0043] Figure 1B A statistical comparison chart showing the differences in average body weight of rats with primary liver cancer in each group before sampling.

[0044] Figure 2 These are morphological photographs of the livers of rats in each group, obtained for the experiment.

[0045] Figure 3 The liver weight of rats with primary liver cancer in each group was ( Figure 3 A) Liver weight / body weight ratio Figure 3 B) Liver weight / spleen weight ratio Figure 3 C) Bar chart comparison.

[0046] Figure 4 Serum ALT (in primary liver cancer rats) Figure 4 A) AST Figure 4 B) ALP Figure 4 C) Content comparison chart.

[0047] Figure 5 HE staining images of liver tissue from rats with primary liver cancer in each group (magnification 200×, 400×). Detailed Implementation

[0048] The present invention will be further illustrated by way of embodiments below, but the present invention is not limited to the scope of the embodiments described herein.

[0049] Example 1

[0050] A traditional Chinese medicine composition comprising the following raw material components:

[0051]

[0052]

[0053] Preparation methods of traditional Chinese medicine preparations:

[0054] 1. Soaking: Place the above-mentioned Chinese herbal medicine composition in a pot and soak it in cold or warm water. The water temperature should not exceed 40℃. The soaking time is 30 to 60 minutes. The amount of water at the beginning of decoction should be 3 to 5 cm above the surface of the medicine.

[0055] 2. Simmering: Simmer twice. The first time, bring to a boil over high heat, then simmer over low heat for 30-50 minutes. The second simmering time should be slightly shorter than the first, about 15 minutes.

[0056] 3. Combine the decoctions from both decoctions and set aside.

[0057] Effect Example

[0058] 1. Experimental Procedure

[0059] A rat model of primary liver cancer was established by intraperitoneal injection of DEN. Male Wistar rats were divided into four groups: a blank control group (C group), a model group (M group), a low-dose group of the traditional Chinese medicine composition (JPHTR-L group), and a high-dose group of the traditional Chinese medicine composition (JPHTR-H group). There were 6 normal rats in the control group and 12 rats in each of the other groups.

[0060] Groups M, JPHTR-L, and JPHTR-H were administered diethylnitrosamine (DEN) (50 mg / kg) via intraperitoneal injection, while group C received an equal volume of physiological saline via intraperitoneal injection, once weekly until week 14. From week 15 onwards: Groups JPHTR-L (at a dose of 12.1 g / kg, according to "Experimental Methodology of Traditional Chinese Medicine Pharmacology," the rat dose is 6.3 times the adult dose, i.e., the low-dose group, i.e., crude drug, is 12.1 g / kg / day) and JPHTR-H (at a dose of 24.2 g / kg, the high-dose group being twice the low-dose group, i.e., crude drug, is 24.2 g / kg / day) were administered a spleen-strengthening and phlegm-resolving formula solution (i.e., the traditional Chinese medicine preparation obtained by decocting as described above) via gavage once daily for 4 weeks; Group M and the blank control group were administered an equal volume of physiological saline via gavage once daily for 4 weeks.

[0061] Patients were kept NPO (nothing by mouth) for 12 hours after the last dose, but were allowed free access to water. The following day, they were weighed and anesthetized with an intraperitoneal injection of 7% chloral hydrate (5 ml / kg). The abdominal cavity was opened, and 5 ml of fresh whole blood was drawn using the abdominal aortic sampling method. After standing for 3 hours, the whole blood was centrifuged at 4°C and 3000 rpm for 15 minutes. Serum was extracted and stored at -80°C. Liver and spleen were harvested sequentially, weighed, and photographed. Liver tissue samples were fixed in 4% paraformaldehyde, while the remaining liver tissue was aliquoted into cryovials, rapidly frozen in liquid nitrogen, and stored at -80°C for later use.

[0062] Serum ALT (alanine aminotransferase), AST (aspartate aminotransferase), and ALP (alkaline phosphatase) levels were analyzed using a Toshiba TBA-40FR fully automated biochemical analyzer. Fresh liver tissue was also stained with hematoxylin and eosin (HE).

[0063] 2. Experimental Results

[0064] (1) During the animal modeling process, the rats in group C were in good condition and no deaths occurred. From the 6th week of modeling, the rats in groups M, JPHT-L, and JPHT-H became lethargic, ate less, had dull and dry fur, and experienced slowed weight gain. From the 10th week onwards, the rats in all four groups gradually developed yellow urine, hematuria, nasal bleeding, and died. After treatment with the traditional Chinese medicine preparation of this invention, their weight recovered slightly.

[0065] Figure 1A The graph shows the change in body weight of rats with primary liver cancer in each group over a period of time each week. Figure 1B A statistical comparison of the differences in average body weight among the groups of rats with primary liver cancer before sampling. Figure 1B The horizontal axis represents the following groups: C: normal group, M: model group, JPHTR-L: low-dose group of traditional Chinese medicine composition, JPHTR-H: high-dose group of traditional Chinese medicine composition. Compared with group C, #: P<0.05; ##: P<0.01; ###: P<0.001. Compared with group M, *: P<0.05; **: P<0.01; ***: P<0.001).

[0066] Figure 2 These are morphological photographs of the livers of rats in each group obtained after the experiment.

[0067] Figure 3 The liver weight of rats with primary liver cancer in each group is shown. Figure 3 A) Liver weight / body weight ratio Figure 3 B) Liver weight / spleen weight ratio Figure 3 C) Bar chart comparison ( Figure 3 Compared with group C, #: P<0.05; ##: P<0.01; ###: P<0.001. Compared with group M, *: P<0.05; **: P<0.01; ***: P<0.001).

[0068] After modeling, two animals died in each of the M, JPHTR-L, and JPHTR-H groups. Except for group C, the livers of all other groups were enlarged to varying degrees, with an uneven surface and visible cancerous nodules of different sizes; liver weight was significantly increased (P<0.001). Figure 3 It can be seen that, compared with group M, there were no significant changes in liver weight, liver-to-body ratio, and liver-to-spleen ratio in groups JPHTR-L and JPHTR-H.

[0069] (2) To study the serum liver function of four groups of rats, Figure 4 Serum ALT (in primary liver cancer rats) Figure 4 A) AST Figure 4 B) ALP Figure 4 C) Content Comparison Chart Figure 4Compared with group C, #: P<0.05; ##: P<0.01; ###: P<0.001. Compared with group M, *: P<0.05; **: P<0.01; ***: P<0.001).

[0070] The comparison showed that, compared with group C, the serum ALT (P<0.001), AST (P<0.01), and ALP (P<0.001) levels in group M were significantly increased. Compared with group M, the AST (P<0.05) and ALP (P<0.05) levels in the JPHTR-L group were significantly decreased, and the same changes were observed in the ALT (P<0.001), AST (P<0.001), and ALP (P<0.01) levels in the JPHTR-H group; however, the ALT level in the JPHTR-L group showed no significant change (P>0.05 indicates no significant change). The significant decrease in AST and ALP levels in the JPHTR-L and JPHTR-H groups compared to group M indicates that both low and high doses can improve liver injury.

[0071] (3) Figure 5 HE staining images (200×, 400×) of liver tissue from rats with primary hepatocellular carcinoma in each group. After HE staining, light microscopic observation revealed that in group C, the liver lobule structure was normal, without inflammation or fibrosis, and the hepatic cords were arranged radially around the central vein. Compared to group C, group M showed destroyed liver lobule structure, disappearance of hepatic plates, formation of pseudolobules, and hepatocytes exhibiting atypical hyperplasia, diffuse edema, fatty degeneration, and necrosis, with enlarged nucleoli. Cancerous cells were observed to be arranged in nests, forming cancer nests, surrounded by abundant inflammatory cell infiltration, rich interstitial sinusoids, and hemorrhage and necrosis in some areas. Intervention with the traditional Chinese medicine composition of this invention (JPHTR-L group and JPHTR-H group) slowed the progression of liver cancer.

[0072] The above results show that the traditional Chinese medicine composition of the present invention can effectively delay the progression of liver cancer.

[0073] While specific embodiments of the present invention have been described above, those skilled in the art should understand that these are merely illustrative examples, and the scope of protection of the present invention is defined by the appended claims. Those skilled in the art can make various changes or modifications to these embodiments without departing from the principles and essence of the present invention, but all such changes and modifications fall within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: Astragalus membranaceus 12-18 parts Polygonatum 12-18 parts 12-18 portions of Polygonum multiflorum 15-21 portions of perilla seeds 12-18 servings of white mustard seeds 12-18 portions of radish seeds 27-33 parts of Scutellaria barbata 7-13 portions of gecko Licorice 3-9 parts.

2. The traditional Chinese medicine composition for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in claim 1, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: Astragalus membranaceus 14-16 parts 14-16 parts of Polygonatum 14-16 portions of Polygonum multiflorum Perilla seeds 17-19 portions 14-16 portions of white mustard seeds 14-16 portions of radish seeds 29-31 parts of Scutellaria barbata 9-11 portions of gecko Licorice 5-7 parts.

3. The traditional Chinese medicine composition for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in claim 2, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: 15 portions of Astragalus membranaceus 15 parts of Polygonatum 15 portions of Polygonum multiflorum 18 portions of perilla seeds 15 portions of white mustard seeds 15 portions of radish seeds 30 portions of Scutellaria barbata 10 geckos Licorice root, 6 parts.

4. The traditional Chinese medicine composition for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in claim 1, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: Astragalus 15 g Polygonatum 15 g Polygonum multiflorum 15 g 18 g of perilla seeds 15g of white mustard seeds 15 g of radish seeds 30 g of Scutellaria barbata 10 g of gecko Licorice 6 g.

5. A method for preparing a traditional Chinese medicine preparation that strengthens the spleen, resolves phlegm, and delays the progression of liver cancer, characterized in that, It includes the following steps: using the traditional Chinese medicine composition for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in any one of claims 1-4 as raw material to prepare the traditional Chinese medicine preparation.

6. The method for preparing the traditional Chinese medicine preparation for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in claim 5, characterized in that, The dosage form of the traditional Chinese medicine preparation is granules, decoction, or paste; And / or, the preparation method of the traditional Chinese medicine preparation includes the following steps: soaking and decocting the traditional Chinese medicine composition, and collecting the decoction.

7. The method for preparing the traditional Chinese medicine preparation for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in claim 6, characterized in that, The solvent used for the soaking is water; And / or, the temperature during immersion is below 40°C; And / or, the soaking time is 30-60 minutes; And / or, the solvent used for the decoction is the liquid or water obtained after the soaking; And / or, during the decoction, the amount of solvent used is such that it covers the surface of the herbal composition by 3-5 cm; And / or, the decoction is performed twice; And / or, the simmering process includes the following steps: bringing to a boil over high heat, then simmering over low heat; And / or, after the decoction, the method further includes one or more of the following steps: filtering, concentrating, and granulating the medicinal liquid; The concentration can be achieved by decoction concentration or by a traditional Chinese medicine concentration machine.

8. The method for preparing the traditional Chinese medicine preparation for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in claim 7, characterized in that, The second frying time is shorter than the first frying time.

9. The method for preparing the traditional Chinese medicine preparation for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in claim 8, characterized in that, The first simmering time is 30-50 minutes, and the second simmering time is 15 minutes.

10. The method for preparing the traditional Chinese medicine preparation for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in claim 8, characterized in that, The decoctions obtained from the two decoctions are mixed to obtain a mixed decoction.

11. A traditional Chinese medicine preparation for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer, which is prepared by the method for preparing the traditional Chinese medicine preparation for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in any one of claims 5-10.

12. The traditional Chinese medicine preparation for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in claim 11, characterized in that, The dosage form of the traditional Chinese medicine preparation is granules, decoction, or paste; And / or, the traditional Chinese medicine preparation may also include excipients.

13. The use of a traditional Chinese medicine composition for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in any one of claims 1-4, or a traditional Chinese medicine preparation for strengthening the spleen, resolving phlegm, and delaying the progression of liver cancer as described in claim 11 or 12, in the preparation of a medicament for delaying the progression of liver cancer.

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