CN112972473B - Medicine for treating adverse reactions of digestive tracts in radiotherapy and chemotherapy of tumors and preparation method thereof - Google Patents

Medicine for treating adverse reactions of digestive tracts in radiotherapy and chemotherapy of tumors and preparation method thereof Download PDF

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CN112972473B
CN112972473B CN202110109655.2A CN202110109655A CN112972473B CN 112972473 B CN112972473 B CN 112972473B CN 202110109655 A CN202110109655 A CN 202110109655A CN 112972473 B CN112972473 B CN 112972473B
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chemotherapy
medicament
radiotherapy
isoalbonone
leucine
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CN112972473A (en
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刘松江
李全
隋博文
李�雨
宋爱英
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Heilongjiang University of Chinese Medicine
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61K33/00—Medicinal preparations containing inorganic active ingredients
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Abstract

The invention relates to a medicine for treating adverse reactions of digestive tracts in radiotherapy and chemotherapy of tumors and a preparation method thereof. The medicament of the invention adopts cyclo- (leucine-tyrosine) and isoalbonone as active ingredients for treating adverse reactions of digestive tracts in tumor radiotherapy and chemotherapy, thereby playing a synergistic effect of the two active ingredients, being beneficial to prolonging the vomit incubation period of patients with tumor radiotherapy and chemotherapy and reducing the vomit and vomit times.

Description

Medicine for treating adverse reactions of digestive tracts in radiotherapy and chemotherapy of tumors and preparation method thereof
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a medicine for treating gastrointestinal adverse reactions of tumor radiotherapy and chemotherapy and a preparation method thereof.
Background
At present, radiotherapy and chemotherapy are the main means of tumor treatment, but radiotherapy and chemotherapy can cause a plurality of adverse reactions such as digestive tract reaction, bone marrow suppression, immunity reduction, organ weakness, inflammation and the like, wherein the digestive tract reaction is the most common, and the incidence rate of the adverse reactions of the digestive tract reaches 77.5-97.4%. Adverse reactions of digestive tract in radiotherapy and chemotherapy comprise anorexia, nausea and vomiting, oral ulcer, abdominal pain, diarrhea and the like. At present, more treatment medicines aiming at the adverse reactions of the digestive tract in radiotherapy and chemotherapy comprise 5-hydroxytryptamine (5-HT) receptor antagonists, antihistamines, phenothiazine medicines and the like, and can improve the reactions of the digestive tract in radiotherapy and chemotherapy to a certain extent. But the use is limited because the medicine also has adverse reaction. For example, antagonists of the 5-HT3 receptor may cause headache, constipation, elevated transaminases, antihistamines having cardiotoxicity; phenothiazines have adverse reactions in the central system and the like. The traditional Chinese medicine can improve the digestive tract reaction caused by radiotherapy and chemotherapy, can enhance the chemotherapy effect, improve the immunity of patients and improve the living quality of the patients, and has the advantage of integral conditioning, so that the traditional Chinese medicine becomes a common method for treating the digestive tract reaction after the radiotherapy and the chemotherapy.
For example, the effect of xiaoqian decoction on the antiemetic effect of a mink emesis model is studied by Linyan and the like, and research results show that the xiaoqian decoction can prolong the mink emesis incubation period caused by three classical emetics, can reduce the mink emesis times caused by cisplatin and apomorphine, and has no obvious difference in the antiemetic effect compared with ondansetron and metoclopramide.
For another example, Tangxing et al, clinical observations of Suye Huanglian Tang in combination with Zusanli Point injection for prevention and treatment of nausea and vomiting associated with cisplatin chemotherapy, in A article, observe clinical effects of Suye Huanglian Tang in combination with Zusanli Point injection for prevention and treatment of nausea and vomiting associated with cisplatin chemotherapy.A method randomly divides 121 patients into two groups, uses tropisetron in a conventional (acute phase D1-3) and intramuscular metoclopramide in a delayed phase (D4-7) during chemotherapy; the treatment group is orally administered with Suyehuanglian decoction in chemotherapy D1-7 on the basis of the control group, delayed phase (D4-7) and Zusanli acupoint injection metoclopramide are administered, the conditions of D3, D7 nausea and vomiting, diarrhea and adverse reaction after chemotherapy of two groups of patients are observed, the remission rate of D3 vomiting in the acute phase is 67.21%, the control group is 61.67%, and the difference of the two groups has no statistical significance (P > 0.05); the incidence rate of severe nausea in the treated group was 31.15% and the control group was 53.33% in the nausea grade, the difference between the two groups was statistically significant (P < 0.05), the remission rate of D7 vomiting in the delayed phase treatment group was 91.80%, the difference between the two groups was 76.67% and the difference between the two groups was statistically significant (P < 0.05); in the nausea degree grading, the incidence rate of severe nausea in a treatment group is 9.84%, the contrast group is 31.67%, the difference of the two groups has statistical significance (P < 0.01), vital signs before and after treatment of the two groups are normal, liver and kidney functions and the like do not change, and adverse reactions do not occur in the treatment group.
However, as a Chinese medicinal prescription preparation, the quality control is difficult due to the complex components. In particular, when it is desired to sell the prepared drug in other countries, there are cases where it is difficult to obtain regulatory approval for the drug with unknown ingredients. Therefore, how to find out real active ingredients from the traditional Chinese medicine formula preparation is a technical problem to be solved urgently in the field.
In the above prior art, pinellia ternate was mentioned as a key factor for preventing nausea and vomiting. Pinellia ternata is a dried tuber of pinellia ternata (pinelliateernata (thunnb.) Breit.) of pinellia genus of Araceae family, and has been used for over 2000 years. The traditional pharmacological actions of pinellia ternate are drying dampness and resolving phlegm, lowering adverse qi and preventing vomiting, relieving distension and fullness and dissipating mass; acute mastitis is externally used, otitis media is taken acutely, and veterinarians are used for treating laryngitis. Further research shows that pinellia ternate also has a plurality of important pharmacological effects of resisting tumor, resisting fertility, reducing blood fat, protecting liver, treating coronary heart disease and the like. The chemical components of pinellia ternata are separated and identified in a lot of documents, but the existing documents do not disclose what components can play a key role in nausea and vomiting.
In addition, folium Perillae is Labiatae, and is an annual herb, and has effects of dispelling pathogenic wind and cold, regulating qi-flowing, relieving epigastric distention, and relieving pain. It is generally believed that the essential oils in perilla leaves play a key role in their pharmaceutical activity.
Based on the prior art, the invention explores key active substances in the Suyehuanglian decoction through experimental research and proves the effects of the active substances through animal experiments
Disclosure of Invention
Based on the reasons, the invention provides a medicament for treating the gastrointestinal adverse reactions of tumor radiotherapy and chemotherapy and a preparation method thereof. Specifically, in order to achieve the purpose of the present invention, the following technical solutions are proposed:
the invention relates to a medicament for treating adverse reactions of digestive tracts in radiotherapy and chemotherapy of tumors, which comprises cyclo- (leucine-tyrosine) shown in a formula (I) and isoalbonone shown in a formula (II)
Figure GDA0003267924590000021
In a preferred embodiment of the invention, the weight ratio of ring- (leucine-tyrosine) to isoalbonone in the medicament is 3-8: 1; preferably 5: 1. The invention can further realize the synergistic interaction between the two active ingredients by reasonably setting the proportion of the two active ingredients.
In another preferred embodiment of the invention, the medicament may or may not include other active ingredients.
In a preferred embodiment of the present invention, the medicament is an injectable formulation; preferably, the injection preparation takes soybean oil for injection as a solvent.
In another aspect, the present invention relates to a process for the preparation of the above mentioned medicament, which comprises dissolving cyclo- (leucine-tyrosine) and isoalbonone simultaneously or separately in soybean oil for injection.
The invention also relates to the application of the medicine, and the medicine is used for preparing the medicine for treating the gastrointestinal adverse reactions of tumor radiotherapy and chemotherapy.
In a preferred embodiment of the present invention, the adverse gastrointestinal reaction is retching and/or vomiting.
In another preferred embodiment of the present invention, the tumor chemoradiotherapy is chemotherapy with cisplatin.
Advantageous effects
The medicament of the invention adopts cyclo- (leucine-tyrosine) and isoalbonone as active ingredients for treating adverse reactions of digestive tracts in tumor radiotherapy and chemotherapy, thereby playing a synergistic effect of the two active ingredients, being beneficial to prolonging the vomit incubation period of patients with tumor radiotherapy and chemotherapy and reducing the vomit and vomit times.
Detailed Description
In order to further understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Unless otherwise specified, the reagents involved in the examples of the present invention are all commercially available products, and all of them are commercially available.
Example 1:
1 materials and methods
Cisplatin injection (20 mg/injection); 5mg of cyclo- (leucine-tyrosine) (dissolved in 2ml of soybean oil for injection), 1mg of isoalbonone (dissolved in 2ml of soybean oil for injection), 5mg of cyclo- (leucine-tyrosine) and 1mg of isoalbonone complex formulation (dissolved in 2ml of soybean oil for injection)
2 laboratory animals
Healthy adult minks weighing 1.5-1.8 kg were male and provided by the animal center of the university of traditional Chinese medicine, Heilongjiang, each animal was placed in a 75cm x 50cm iron cage independently, irradiated with natural light for 24h, and had free access to drinking water before the experiment.
3 Experimental methods
Grouping and administration of cisplatin as an agonist.
Randomized into 5 groups of 10: a normal control group, a model control group, a cyclo- (leucine-tyrosine) treatment group, an isoalbonone treatment group and a compound preparation treatment group. The components are injected with normal saline (2ml kg)-1) Physiological saline (2 ml/kg)-1) 5mg cyclo- (leucine-tyrosine), 1mg isoalbonone, 5mg cyclo- (leucine-tyrosine) and 1mg isoalbonone complex formulation. The cisplatin is injected into abdominal cavity once a day for 3 days after continuous administration, except for normal control group, cisplatin 7.5 mg/kg is administered-1. The incubation period, retching and vomiting times for the beginning of retching and vomiting of each group of minks were recorded within 6h after cisplatin injection.
4 statistical treatment
The metering data are tested by group or pairing t, the data are expressed by (x +/-s), and the counting data are tested by chi-square.
5 results of the experiment
Table 1: therapeutic effect of medicine on cisplatin-induced mink emesis model
Figure GDA0003267924590000041
Note: p <0.05 compared to control group
The experimental results show that the incubation period of the compound preparation treatment group is obviously longer than that of the model group, the times of retching and vomiting are obviously less than that of the model group, and the treatment effect of the separate cyclo- (leucine-tyrosine) or the isoalbonone on the vomiting model is not obvious.
The foregoing describes preferred embodiments of the present invention, but is not intended to limit the invention thereto. Modifications and variations of the embodiments disclosed herein may be made by those skilled in the art without departing from the scope and spirit of the invention.

Claims (9)

1. A medicine for treating adverse reactions of digestive tracts in radiotherapy and chemotherapy of tumors comprises the active ingredients of cyclo- (leucine-tyrosine) shown in formula (I) and isoalbonone shown in formula (II),
Figure FDA0003267924580000011
2. the medicament of claim 1, wherein the weight ratio of ring- (leucine-tyrosine) to isoalbonone in the medicament is 3-8: 1.
3. The medicament of claim 1, wherein the weight ratio of ring- (leucine-tyrosine) to isoalbonone in the medicament is 5: 1.
4. The medicament according to any one of claims 1 to 3, which is an injectable formulation.
5. The pharmaceutical composition according to claim 4, wherein the injectable preparation comprises soybean oil for injection as a solvent.
6. A process for the preparation of a medicament according to claim 5, which comprises dissolving cyclo- (leucine-tyrosine) and isoalbonone simultaneously or separately in soybean oil for injection.
7. The use of the medicament of any one of claims 1 to 5 for the manufacture of a medicament for the treatment of adverse gastrointestinal effects of tumor radiotherapy and chemotherapy.
8. The use according to claim 7, wherein the gastrointestinal adverse effect is emesis.
9. The use according to claim 7, wherein the tumor chemoradiotherapy is chemotherapy with cisplatin.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120053415A (en) * 2010-11-17 2012-05-25 한국원자력연구원 Composition for prevention and treatment of cancer comprising isoegomaketone as an active ingredient
CN103224572A (en) * 2012-01-31 2013-07-31 岳旺 Preparation of alginic acid cerium complex and application of alginic acid cerium as antiemetic drugs
CN106459151A (en) * 2014-06-20 2017-02-22 三得利控股株式会社 Cyclic dipeptide-containing composition

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120053415A (en) * 2010-11-17 2012-05-25 한국원자력연구원 Composition for prevention and treatment of cancer comprising isoegomaketone as an active ingredient
CN103224572A (en) * 2012-01-31 2013-07-31 岳旺 Preparation of alginic acid cerium complex and application of alginic acid cerium as antiemetic drugs
CN106459151A (en) * 2014-06-20 2017-02-22 三得利控股株式会社 Cyclic dipeptide-containing composition

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
Anti-inflammatory constituents from Perilla frutescens on lipopolysaccharide-stimulated RAW264.7 cells;Xiao-Feng Wang等;《Fitoterapia》;20180816;第130卷;第61-65页 *
Ethnomedicinal, Phytochemical and Pharmacological Investigations of Perilla frutescens (L.) Britt.;Hiwa M. Ahmed;《Molecules》;20181228 *
Isoegomaketone induces apoptosis through caspase-dependent and caspase -independent pathways in human DLD1 cells;Byoung Ok CHO等;《Biosci. Biotechnol. Biochem.》;20110707;第75卷(第7期);第1306-1311页 *
半夏生物碱含量测定及止呕研究;王蕾等;《中国药理学通报》;20050731;第21卷(第7期);第864-867页 *
半夏的化学成分、药理作用及毒性研究进展;王依明等;《中国药房》;20201231;第31卷(第21期);第2676-2682页 *
紫苏异酮对人结直肠癌裸鼠移植瘤放疗增敏作用及其分子机制的初步研究;吴冠楠等;《肿瘤综合治疗电子杂志》;20201231;第6卷(第2期);第109-112页 *
紫苏异酮对肝癌细胞的放疗增敏及其作用机制研究;吴志瑛;《临床医药实践》;20160430;第25卷(第4期);第279-280、285页 *
苏叶黄连汤联合足三里穴位注射防治顺铂化疗相关恶心呕吐的临床观察;唐星等;《中国中医急症》;20180930;第27卷(第9期);第1621-1623页 *

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