CN112999271A - Red date powder processed product for enhancing cyclophosphamide anti-tumor curative effect and using method thereof - Google Patents
Red date powder processed product for enhancing cyclophosphamide anti-tumor curative effect and using method thereof Download PDFInfo
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Abstract
The invention discloses a red date powder processed product for enhancing the anti-tumor curative effect of cyclophosphamide and a using method thereof. The red date powder processed product or the composite product of the red date powder processed product and the dietary fiber can be prepared into any one of the following products 1) to 3): 1) products for enhancing the antitumor efficacy of cyclophosphamide; 2) a product for enhancing the anti-tumor curative effect of the combination of cyclophosphamide and other anti-tumor drugs; 3) a product for relieving bone marrow depression caused by cyclophosphamide. The red date powder processed product can be used for enhancing the anti-tumor effect of cyclophosphamide (or other anti-tumor drugs), and when the red date powder processed product is used in combination with cyclophosphamide, the tumor volume, such as colon tumor, can be remarkably reduced. The red date powder processed product can also relieve bone marrow suppression caused by cyclophosphamide.
Description
Technical Field
The invention relates to a red date powder processed product for enhancing the anti-tumor curative effect of cyclophosphamide and a using method thereof, belonging to the technical field of functional foods.
Background
Cyclophosphamide is one of the most commonly used alkylating agent antineoplastic drugs, and is clinically used for treating non-hodgkin lymphoma, multiple myeloma, leukemia, breast cancer, lung cancer and the like, alone or in combination with other chemotherapeutic drugs. Cyclophosphamide is metabolized in the liver to produce cyclophosphamide mustard, a cell cycle non-specific alkylating agent that acts on the S phase of cell division, and is cytotoxic by affecting DNA synthesis.
At present, cyclophosphamide is widely used in tumor treatment, but the occurrence of tumor drug resistance seriously restricts the curative effect of cyclophosphamide. Research shows that the anti-tumor effect of cyclophosphamide has obvious dose-effect characteristics, the dosage strength of the cyclophosphamide is improved, the curative effect can be obviously improved, and the dosage strength of the cyclophosphamide is one of the key factors for predicting the survival period in the treatment of some tumors (such as non-Hodgkin's lymphoma). However, cyclophosphamide has a narrow therapeutic window, and high dose administration causes severe side effects such as hepatotoxicity, bladder toxicity, bone marrow suppression, etc. In particular, its severe myelosuppressive effects make high dose therapy difficult to maintain. In addition, cyclophosphamide is also an immunosuppressant, and the damage of the immune function caused by the cyclophosphamide not only affects the immunity of tumor patients, but also has adverse effect on the treatment of tumors.
Enhances the anti-tumor effect of cyclophosphamide, reduces the toxic and side effects when the cyclophosphamide is taken at high dose, and has important significance for the anti-tumor treatment of the cyclophosphamide. The red dates are representative of medicine and food, and the red dates contain components such as polysaccharide, polyphenol, organic acid and the like, so that the red dates have the effects of enhancing hematopoiesis and immunity. Therefore, the application of the red date powder in relieving the side effect caused by cyclophosphamide chemotherapy drugs and improving the anti-tumor effect of the cyclophosphamide chemotherapy drugs is necessary to be researched.
Disclosure of Invention
The invention aims to provide the application of the red date powder processed product in enhancing the anti-tumor curative effect of cyclophosphamide and simultaneously relieving bone marrow suppression caused by cyclophosphamide.
Specifically, the invention provides an application of a red date powder processed product or a composite product of the red date powder processed product and dietary fiber in preparing any one of the following products 1) -3):
1) products for enhancing the antitumor efficacy of cyclophosphamide;
2) a product for enhancing the anti-tumor curative effect of the combination of cyclophosphamide and other anti-tumor drugs;
3) a product for relieving bone marrow depression caused by cyclophosphamide.
The red date powder processed product adopted by the invention is red date full-component dry powder or a product taking the red date full-component dry powder as an active ingredient.
The product taking the red date full-component dry powder as the active ingredient is a suspension containing the red date full-component dry powder, a compressed tablet containing the red date full-component dry powder or a capsule containing the red date full-component dry powder.
The composite product of the red date powder processed product and the dietary fiber is a product taking red date full-component dry powder and the dietary fiber as active ingredients, wherein the mass fraction of the red date full-component dry powder is not less than 50%, and the dietary fiber is dietary cellulose or resistant starch. The product taking the red date full-component dry powder and the dietary fiber as active ingredients is a suspension containing the red date full-component dry powder and the dietary fiber, a tabletting agent containing the red date full-component dry powder and the dietary fiber or a capsule containing the red date full-component dry powder and the dietary fiber.
The red date full-component dry powder adopted by the invention can be obtained by crushing and screening dried red dates in multiple steps in a low-temperature environment, and can be carried out under conventional conditions, such as the following conditions:
removing core of fructus Jujubae, cutting into slices with thickness not more than 2mm, placing into vacuum drying oven, drying at 40 deg.C and vacuum degree of 0.07MPa for 72 hr until water content is 5% (wet basis); then, pre-crushing the red dates to 50 meshes by using a traditional Chinese medicine crusher, and in the pre-crushing process, adopting a mode of multiple crushing and intermediate cooling to ensure that the temperature of red date slices in the crushing process does not exceed 40 ℃; then, carrying out deep cooling on the pre-crushed material by using liquid nitrogen, and further crushing the pre-crushed material to below 200 meshes (the screening particle size is 75mm) by using an ultrafine crusher;
the particle size range of the red date full-component dry powder is 1-100 mu m.
The red date full-component dry powder adopted by the invention comprises water-soluble components and water-insoluble components in natural red dates;
in the red date full-component dry powder, the mass fraction of the water-soluble components is 50-80%, wherein the mass content of total sugar is not less than 60% of the total mass of the water-soluble components in terms of glucose, for example, in the red date powder processed product adopted by the specific embodiment of the invention, the mass content of total sugar is 75% and 83% of the total mass of the water-soluble components, and the mass content of water-soluble polysaccharide (key component) is not less than 15% of the total mass of the water-soluble components, for example, in the red date powder processed product adopted by the specific embodiment of the invention, the mass content of water-soluble polysaccharide is 28% and 34% of the total mass of the water-;
the water-soluble component also comprises a flavonoid compound, and the content of the flavonoid compound is as follows: every 100g of the red date full-component dry powder is not less than 1.5 mg.
In the red date full-component dry powder, the mass content of non-starch polysaccharide (key component) is 40-90% of the total amount of the water-insoluble component, and in the red date powder processed product adopted by the specific embodiment of the invention, the mass content of non-starch polysaccharide is 50% and 68% of the total amount of the water-insoluble component.
The non-starch polysaccharide contains red date crude fiber, the mass content of the red date crude fiber is not less than 15% of the total amount of the water-insoluble components, and in the red date powder processed product adopted by the specific embodiment of the invention, the mass content of the red date crude fiber is 22.6% and 25% of the total amount of the water-insoluble components.
The red date powder processed product can be taken in the following way:
continuously orally taking the red date powder processed product within 3 days no later than the first use of the cyclophosphamide, wherein the daily oral administration dosage is 0.04-0.25 g/kg of body weight, and specifically 0.06-0.12 g/kg of body weight; is taken once or in several times;
the administration is continued for at least 12 days.
The compound product of the red date powder processed product and the dietary fiber can be taken in the following mode
Continuously orally taking the red date powder processed product and the dietary fiber composite product within 3 days no later than the first use of the cyclophosphamide, wherein the oral dose of the red date powder processed product and the dietary fiber composite product is 0.02-0.25 g/kg of body weight, specifically 0.04-0.12 g/kg of body weight, in terms of the red date whole-component dry powder contained in the red date powder, and the red date powder processed product and the dietary fiber composite product are taken at one time or in several times;
the administration is continued for at least 12 days.
The red date powder processed product can be used for enhancing the anti-tumor effect of cyclophosphamide (or other anti-tumor drugs), and when the red date powder processed product is used in combination with cyclophosphamide, the tumor volume, such as colon tumor, can be remarkably reduced. The red date powder processed product can also relieve bone marrow suppression caused by cyclophosphamide.
Drawings
FIG. 1 shows that the red date powder processed product enhances the effect of cyclophosphamide on MC38 colon cancer mice (tumor volume change).
FIG. 2 shows the effect of cyclophosphamide therapy on MC38 colon cancer mice (tumor volume change) in combination of processed red date powder and dietary fiber.
FIG. 3 is a bar graph showing the decrease of leukocytes caused by cyclophosphamide reduction in processed red dates.
Detailed Description
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
The red date powder processed product is applied to enhancing the anti-tumor curative effect of cyclophosphamide and relieving the bone marrow suppression effect caused by cyclophosphamide.
The red date powder used in the following examples was prepared as follows:
removing cores of red dates, cutting the red dates into slices with the thickness not more than 2mm, then placing the slices into a vacuum drying oven, drying for 72 hours at the temperature of 40 ℃ and the vacuum degree of 0.07MPa until the water content is 5% (wet basis), then pre-crushing the slices to 50 meshes by using a traditional Chinese medicine crusher, and in the pre-crushing process, adopting a mode of multiple crushing and intermediate cooling to ensure that the temperature of the red date slices in the crushing process is not more than 40 ℃; then, the pre-crushed material is subjected to deep cooling by liquid nitrogen, and then is further crushed to below 200 meshes (the screening particle size is 75mm) by an ultrafine crusher.
The particle size of the prepared red date powder is 10-100 microns.
TABLE 1 Main component content of two red date powders (g, both based on 100g of oven-dried red date powder)
MC38 colon cancer cell line used in the following examples was purchased from a national experimental cell resource sharing platform, and MC38 colon cancer mouse model used in the following examples can be obtained according to the following procedures described in the literature: differences in response of PD-1 inhibitors in different mouse tumor models were explored, and the proceedings of the military medical college were liberated, 2019,40 (4).
Examples 1,
This example is the use of red date powder to enhance the effect of Cyclophosphamide (CTX) in the treatment of MC38 colon cancer mice.
The adopted tumor model animal is an MC38 colon cancer mouse model, 80mg/kg of cyclophosphamide is injected into the abdominal cavity of each mouse for treatment for three consecutive days on the 7 th to 10 th days after tumor inoculation, and the same amount of physiological saline is injected into the abdominal cavity of a blank control group. The mice bearing tumor were gavaged with red date powder at a dose of 0.8g/kg per day for 12 days from the start of cyclophosphamide injection, one group using red date powder A and the other group using red date powder B, while mice treated with cyclophosphamide only were used as controls (6 mice per group).
After 21 days of treatment, the change of the tumor volume of each group of mice is shown in figure 1, and it can be seen that the tumor volume of the group treated with the red date powder is reduced by 62.8% and 68.4% compared with the control group only using cyclophosphamide; tumor volume was reduced by 97.3% and 97.7% compared to the placebo group.
Examples 2,
This example is the use of red date powder a in combination with resistant starch to enhance the effect of cyclophosphamide in the treatment of MC38 colon cancer mice.
Tumor inoculation and cyclophosphamide injection were performed as in example 1.
The method comprises the steps of adopting red date powder A and resistant starch from the beginning of cyclophosphamide injection, performing intragastric administration on tumor-bearing mice for 12 days according to the dosage of 0.6g/kg of red date powder A and 0.2g/kg of resistant starch every day, and taking mice only treated by cyclophosphamide as controls (each group is 6 mice).
After 21 days of treatment, the change of the tumor volume of each group of mice is shown in the attached figure 2, and it can be seen that the tumor volume of the group treated with the red date powder and the resistant starch in an auxiliary way is reduced by 69.4 percent compared with the control group only using cyclophosphamide; tumor volume was reduced by 96.9% compared to the placebo group.
Examples 3,
This example is to reduce bone marrow suppression by cyclophosphamide using red date processed products.
The model animal used was C57/BL6J, and cyclophosphamide was intraperitoneally injected for three consecutive days at 80mg/kg, after which time administration of red date powder was started, and mice were gavaged at a dose of 0.8g/kg per day, and red date powder A was administered for 12 days, while mice receiving cyclophosphamide only were used as controls (6 mice per group).
The change in white blood cells after 12 days in each group of mice is shown in FIG. 3. It can be seen that compared with the blank control group, the proportion of the white blood cells of the cyclophosphamide-only group and the red date powder A-assisted treatment group is respectively reduced by 49% and 21%, and compared with the control group using the cyclophosphamide, the white blood cell number of the red date powder A-assisted treatment group is restored by 54%, which indicates that the red date powder can obviously reduce the bone marrow suppression caused by the cyclophosphamide.
Claims (10)
1. The application of the red date powder processed product or the composite product of the red date powder processed product and the dietary fiber in the preparation of any one of the following products 1) -3):
1) products for enhancing the antitumor efficacy of cyclophosphamide;
2) a product for enhancing the anti-tumor curative effect of the combination of cyclophosphamide and other anti-tumor drugs;
3) a product for relieving bone marrow depression caused by cyclophosphamide.
2. A composition with any function of a) to c) comprises a red date powder processed product and cyclophosphamide;
a) enhancing the anti-tumor efficacy of cyclophosphamide;
b) enhancing the anti-tumor efficacy of the combination of cyclophosphamide and other anti-tumor drugs;
c) relieving bone marrow suppression caused by cyclophosphamide.
3. A composition with any one of the following A) -C) functions comprises fructus Jujubae powder processed product, dietary fiber and cyclophosphamide;
A) enhancing the anti-tumor efficacy of cyclophosphamide;
B) enhancing the anti-tumor efficacy of the combination of cyclophosphamide and other anti-tumor drugs;
C) relieving bone marrow suppression caused by cyclophosphamide.
4. The use according to claim 1 or the composition according to claim 2 or 3, characterized in that: the red date powder processed product is red date full-component dry powder or a product taking the red date full-component dry powder as an active ingredient.
5. The use or composition according to claim 4, characterized in that: the product taking the red date full-component dry powder as the active ingredient is a suspension containing the red date full-component dry powder, a compressed tablet containing the red date full-component dry powder or a capsule containing the red date full-component dry powder.
6. The use according to claim 1 or 4 or 5 or the composition according to any one of claims 2 to 5, characterized in that: the composite product of the red date powder processed product and the dietary fiber is a product taking red date full-component dry powder and the dietary fiber as active ingredients, wherein the mass fraction of the content of the red date full-component dry powder is not less than 50%, and the dietary fiber is dietary cellulose or resistant starch.
7. Use or composition according to claim 6, characterized in that: the product taking the red date full-component dry powder and the dietary fiber as active ingredients is a suspension containing the red date full-component dry powder and the dietary fiber, a tabletting agent containing the red date full-component dry powder and the dietary fiber or a capsule containing the red date full-component dry powder and the dietary fiber.
8. The use according to any one of claims 1 or 4 to 7 or the composition according to any one of claims 2 to 7, characterized in that: the red date full-component dry powder is obtained by crushing and screening dried red dates in multiple steps in a low-temperature environment;
the particle size range of the red date full-component dry powder is 1-100 mu m.
9. The use according to any one of claims 1 or 4 to 8 or the composition according to any one of claims 2 to 8, characterized in that: the red date full-component dry powder comprises water-soluble components and water-insoluble components in natural red dates;
in the red date full-component dry powder, the mass fraction of the water-soluble components is 50-80%, wherein the mass content of total sugar is not less than 60% of the total mass of the water-soluble components, and the mass content of water-soluble polysaccharide is not less than 15% of the total mass of the water-soluble components;
in the red date full-component dry powder, the mass content of the non-starch polysaccharide is 40-90% of the total amount of the water-insoluble components.
10. Use or composition according to claim 9, characterized in that: the water-soluble component also comprises a flavonoid compound, and the content of the flavonoid compound is as follows: every 100g of the red date full-component dry powder is not less than 2 mg;
the non-starch polysaccharide contains red date crude fiber, and the content of the red date crude fiber is not less than 15% of the content of the water-insoluble component.
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| CN202110239156.5A CN112999271A (en) | 2021-03-04 | 2021-03-04 | Red date powder processed product for enhancing cyclophosphamide anti-tumor curative effect and using method thereof |
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| CN202110239156.5A CN112999271A (en) | 2021-03-04 | 2021-03-04 | Red date powder processed product for enhancing cyclophosphamide anti-tumor curative effect and using method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113940425A (en) * | 2021-10-27 | 2022-01-18 | 新疆天辰智慧信息科技有限公司 | Red date fermented product for relieving bone marrow suppression caused by chemotherapy and preparation method thereof |
-
2021
- 2021-03-04 CN CN202110239156.5A patent/CN112999271A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 朱虎虎等: "新疆大枣的抗肿瘤作用", 《中国实验方剂学杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113940425A (en) * | 2021-10-27 | 2022-01-18 | 新疆天辰智慧信息科技有限公司 | Red date fermented product for relieving bone marrow suppression caused by chemotherapy and preparation method thereof |
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