CN1261141C - Medicine prepn for preventing and retarding side effect of chemotherapy and its prepn process - Google Patents

Abstract

The present invention relates to a preparation for preventing or retarding the side effect of chemotherapy and a preparation method thereof, particularly to a traditional Chinese medicine preparation for preventing or retarding the large damage to hemopoietic systems, immunological functions, digestive systems, etc. caused by tumour chemotherapy, and the damage causes chemotherapy can not be executed step by step. The preparation is prepared by the following steps: pulverizing red ginseng, milkvetch root, Chinese angelica, Radix Asparagi, psoralea fruit, barbary wolfberry fruit, slenderstyle acanthopanax bark, red sage root, honeysuckle flower and licorice root; extracting through refluxing by 80% ethanol, decocting by water, filtering, depressurizing, and then concentrating to obtain extract; pulverizing the extract, uniformly mixing, drying, processing through pulverizing, and then preparing to obtain the preparation. The preparation is used together with chemotherapy to obtain the functions of relieving the suppression of chemotherapy on the marrow, increasing the intracorporeal level of leucocyte, platelet and protoheme, enhancing the immunological functions of patients, increasing the ratio of CD3 to CD4/CD8, reducing the side reaction of chemotherapy, protecting the marrow, liver and renal functions to a certain degree and lightening or releasing the side effect caused by chemotherapy so as to cause the patients to successfully complete combined chemotherapy, and the total effective rate of preventing or retarding the side effect of chemotherapy can reach 90.48%.

Description

Prevention or slow down preparation of chemotherapy side effect and preparation method thereof

Technical field the present invention relates to a kind ofly prevent or slow down chemotherapy of tumors that hemopoietic system, immunologic function, digestive system etc. are caused bigger infringement, the Chinese medicine preparation that chemotherapy can not be implemented set by step.

The background technology malignant tumor is the difficult illness of serious harm human health and life, occupies first of the disease death rate.Surgical treatment, X-ray therapy and chemotherapy are generally taked in the treatment of current malignant tumor.Chemotherapy accounts for larger proportion in whole oncotherapy, develop very soon over nearly 40 years, and curative effect improves constantly.But, chemotherapy has very big shortcoming, and it is not strong to the selective inhibitory of tumor cell, and systemic administration has bigger toxicity.The hemopoietic system that chemotherapy causes, digestive system and immune damage often bring new misery to the patient, cause chemotherapy system implementation set by step, make many patients be forced to the Halfway Stopping chemotherapy.

Chinese medicine obtained generally approving and promoting recently as the chemotherapy auxiliary treatment means, is primarily aimed at bone marrow toxicity that chemotherapy causes, gastrointestinal toxicity reaction regulating liver-QI, renal damage etc. and carries out prophylactic treatment and symptomatic treatment.Wherein, people particularly pay attention to leukopenia caused by cancer chemotherapy disease, have accumulated the treatment experience of comparison system.The loyal soup decoction of the strand of forming by Herb Gynostemmae Pentaphylli, Fructus Ligustri Lucidi, Caulis Spatholobi, Fructus Psoraleae of Liu Shi, average medication 4.65 days, total effective rate promptly reaches 90.0%, and function of increasing leukocyte is remarkable.Zhou Shi forms the blood glue oral liquid by white phoenix glue, rivers and mountains fat, Wang Lu juice, through contrasting with batilol powder group, treat after 7 days, two groups of difference produce effects 102,19 examples, good 126,33 examples, effective 59,20 examples, invalid 42,54 examples of imitating, total effective rate 87.2%, 57.1%, average leukocyte increasing 1.665 * 10 ⁹L, 0.96 * 10 ⁹L (P＜0.01), curative effect obviously is better than matched group.Xu Shi adds Ke's Fructus Lycii, Colla Corii Asini, Caulis Spatholobi, Rhizoma Polygoni Cuspidati, Rhizoma Dioscoreae, Radix Codonopsis, the Radix Paeoniae Alba, the Rhizoma Atractylodis Macrocephalae, Radix Glycyrrhizae 9 flavors on the Radix Angelicae Sinensis decoction for tonifying blood basis, day 1 dose is decocted in water for oral dose, and contrasts with leucogen and batilol combination group, and curative effect is seen excellent aspect leukocyte increasing.Zhai Shi gets the Radix Astragali, Rhizoma Polygonati, Semen Coicis, Fructus Lycii, Radix Codonopsis, Fructus Psoraleae, Radix Glycyrrhizae Preparata and forms and rise plain soup,, adds with deficiency of spleen-QI and stomach-QI, blood deficiency, the deficiency of YIN, all cards of yang deficiency and to simplify sanction for square substantially with it, and 2 weeks were 1 course of treatment, total effective rate 89%.The setting upright of Li Shi rises plain soup the Radix Astragali, Radix Codonopsis, Rhizoma Polygonati, Radix Angelicae Sinensis, Fructus Psoraleae, the Rhizoma Atractylodis Macrocephalae, Poria, Fructus Ligustri Lucidi and Radix Polygoni Multiflori 9 flavors.Based on it, with the card plus-minus, deficiency of both QI and blood is Radix Ginseng, Colla Corii Asini, Radix Rehmanniae Preparata, Caulis Spatholobi 4 flavor punishments more, have also obtained satisfied curative effect aspect leukocyte increasing.Zheng Shi then gets pearl and gives ginseng, Rhizoma Polygonati, Radix Pseudostellariae, the Radix Astragali, Fructus Ligustri Lucidi, Radix Angelicae Sinensis, Fructus Psoraleae etc. 10 flavor and form to support and just rising plain soup, day 1 dose of decocting, divide 3 times oral, 10 was 1 course of treatment, produce effects 39 examples, effective 8 examples, invalid 3 examples.He Shi is made into Chinese angelica blood supplementing Cortex Phellodendri soup with Radix Angelicae Sinensis, the Radix Astragali, Cortex Phellodendri.

Be not difficult to find out from above, commonplace in the used medicine with medicinal applications such as the Radix Astragali, Radix Angelicae Sinensis, Radix Codonopsis, Caulis Spatholobi, Fructus Ligustri Lucidi, Fructus Psoraleae, Rhizoma Polygonati, Fructus Lycii, prove them based on benefiting vital QI and blood, the QI and blood deficiency of having given counterevidence is that the basic pathology that chemical therapy toxic side effect causes changes.Thereby benefiting vital QI and blood becomes the complementary and preventative-therapeutic basic rule of treatment of Chinese medicine naturally.

Summary of the invention the objective of the invention is at above-mentioned present situation, aim to provide a kind of can the prevention or slow down chemotherapy of tumors hemopoietic system, immunologic function, digestive system etc. caused bigger infringement, the Chinese medicine preparation that chemotherapy can not be implemented set by step.

The implementation of the object of the invention is, prevents or slow down the preparation of chemotherapy side effect, and it is made by following materials of weight proportions medicine:

Radix Ginseng Rubra 15g-24g Radix Astragali 15g-24g Radix Angelicae Sinensis 6g-12g

Radix Asparagi 15g-24g Fructus Psoraleae 10g-15g Fructus Lycii 9g-15g

Cortex Acanthopancis 6g-10g Radix Salviae Miltiorrhizae 8g-12g Flos Lonicerae 8g-12g

Radix Glycyrrhizae 5g-8g.

Prevention or the preparation method of slowing down the preparation of chemotherapy side effect, its concrete steps are:

1) the 15g-24g red ginseng powder is broken into fine powder, the CO2 supercritical extraction,

2) the 15g-24g Radix Astragali, 6g-12g Radix Angelicae Sinensis, 8g-12g Radix Salviae Miltiorrhizae, 10g-15g Fructus Psoraleae, 6g-10g Cortex Acanthopancis add 80% alcohol reflux secondary, add 8 times of amounts for the first time, extract 2 hours, add 6 times of amounts for the second time, extract 1.5 hours, filter, and get filtrate 1, filtering residue;

3) filtering residue and 15g-24g Radix Asparagi, 9g-15g Fructus Lycii, 8g-12g Flos Lonicerae, 5g-8g Radix Glycyrrhizae decoct with water twice, add 8 times of water gagings for the first time, decoct 2 hours, add 8 times of water gagings for the second time, decoct 1.5 hours, filter, and get filtrate 2;

4) filtrate 1,2 is merged, the relative density that is evaporated to 60 ℃ under is a 1.30-1.32 extractum, extractum and Radix Ginseng Rubra fine powder mixing, 60-70 ℃ time drying, pulverize product.

Product adds an amount of dextrin, and mixing adds ethanol and makes granular preparation.Can get tablet, powder or capsule etc. by general pharmaceutical technology.

Because deficiency of both QI and blood symptoms such as spiritlessness and weakness, lusterless complexion, nausea and vomiting, lack of appetite be indigestion and loss of appetite appear in tumor patient mostly after chemotherapy, so this preparation is primarily aimed at the deficiency of both QI and blood prescription of making laws.Radix Ginseng Rubra, the Radix Astragali and Radix Angelicae Sinensis 3 flavors are monarch drug in the prescription, and Radix Ginseng Rubra, the Radix Astragali are mended solid invisible gas rapidly, and two medicines combine harmoniously, and bring out the best in each other, and more go into Radix Angelicae Sinensis benefit blood and battalion, the void of tonifying five ZANG-organs, if this, Yin grows while yang is generating, gas is congested multiple, qi and blood tonifying; Because of essence and blood sharing the same origin, cloudy blood alternate transforms between essence, blood, the cloudy three mutually, share so get Fructus Psoraleae, Cortex Acanthopancis, Fructus Lycii three flavors, and invigorating the liver and kidney, beneficial vital essence adds the Radix Asparagi nourishing YIN to relieve dryness again, and the auxiliary altogether monarch drug tonify deficiency of four flavors is set upright, in case QI and blood consumption wound is ministerial drug;

Other gets the Radix Salviae Miltiorrhizae nourishing blood and promoting blood circulation, makes the monarch and his subjects' medicine tonify without causing stagnation; The Flos Lonicerae merit is arrogated to oneself detoxifcation, in case pathogen takes advantage of a weak point, the Radix Glycyrrhizae detoxifcation, in case evil poison is killd the evil of cutting down, Radix Glycyrrhizae with itself and in, the preface of burnt lifting in the coordination is mended the power of strong Central Region fortuneization; With its detoxifcation, dispel the heresy poison that chemotherapy is stopped over.More than 3 flavors, assistant helps all medicines of the monarch and his subjects, in case biased mistake of not capturing, so be adjuvant drug. But Radix Glycyrrhizae is coordinating the actions of various ingredients in a prescription again, holds concurrently to be messenger drug in the side.

In this preparation ten flavor medicine, using medicines of both cold and hot natures simultaneously, property is gentle partially, qi and blood tonifying, it is empty to set upright reason, and separates the poison of chemotherapy, corrects and remove the evil that chemotherapy is cut down kiling of tumor patient, and attenuation to be to increase the effect of chemotherapy, forms prevention of diseae, the disease merit of curing the disease.

This preparation and chemotherapy combined administration can alleviate the inhibition of chemotherapy to bone marrow, and the level of leukocyte, platelet and haemachrome in the rising body improves patient's immunologic function, improves CD ₃And CD ₄/ CD ₈Ratio, the side reaction that alleviates chemotherapy has the certain protection effect to bone marrow, liver, renal function.Can alleviate or alleviate the toxic and side effects that chemotherapy causes, make the patient finish combined chemotherapy smoothly, prevent or the total effective rate that slows down chemotherapy side effect is 90.48%.

Preparation method of the present invention is scientific and reasonable, adopts CO2 supercritical extraction, spray-dired vanguard technology, makes product recovery rate height, the preparation determined curative effect.

The specific embodiment

Formulation Example of the present invention (g) sees the following form:

	1	2	3	4	5	6	7
								Radix Ginseng Rubra	15	16	17	18	21	22	24
The Radix Astragali	18	21	19	24	19	16	15
								Radix Angelicae Sinensis	24	20	21	15	17	19	18
Radix Asparagi	16	15	20	24	18	19	22
								Fructus Psoraleae	10	11	12	13	14	14	15
Fructus Lycii	11	15	12	9	14	10	13
								Cortex Acanthopancis	10	6	8	8	7	9	7
Radix Salviae Miltiorrhizae	10	11	8	9	10	11	14
								Flos Lonicerae	8	10	10	8	9	12	8
Radix Glycyrrhizae	6	7	8	5	6	7	8

The pharmacodynamic study that the Shenyang City carries out at secondary sieve medical science and technology center shows, when this granular preparation dosage is respectively to 2.81g/kg, 5.63g/kg, 11.26g/kg, normal mouse is used cyclophosphamide reach mice S _ISOThe cyclophosphamide chemotherapeutic toxicity all has tangible Attenuation.

Hemogram and Biochemical Research result show that (30mg/kg * 7d) compare with the normal saline matched group, leukocyte and bone marrow nucleated cell significantly reduce (P＜0.01) to the cyclophosphamide group, present stronger toxic reaction.Injection give cyclophosphamide the time this granular preparation of mouse gavaging (2.81g/kg, 5.63g/kg, 11.26g/kg) and positive control drug SHENQI PIAN (2.5/kg), 3 dosage groups of this preparation and SHENQI PIAN group all significantly alleviate leukocyte, the bone marrow center cell number decline (P＜0.01) that cyclophosphamide causes, this granular preparation has tangible dose-dependence, and the leukocyte that big or middle dosage group and SHENQI PIAN group cause tumor-bearing mice cyclophosphamide chemotherapy, bone marrow nucleated cell number descend to also having and significantly alleviate effect (P＜0.01);

Pathologic finding shows, this granular preparation is used the hepatic injury that cyclophosphamide and tumor-bearing mice cyclophosphamide chemotherapy cause to normal mouse all protective effect, and tangible dose-dependence is arranged: to mice S _ISOThe solid tumor growth also has the obvious suppression effect, and certain repeatability is arranged; The toxicity that the cyclophosphamide chemotherapy is caused has Attenuation.

The acute toxicity test of this granular preparation shows, with 15g/kg gastric infusion (be equivalent to the clinical ampoule of people 128 times), in 7 days, no poisoning symptom performance proves that this granular preparation acute toxicity is little, takes safety to mice.

Institute of oncology, Shenyang City, the 5th the People's Hospital, Shenyang City have carried out clinical observation with this preparation oral liquid to prevention and the caused toxic and side effects of adjuvant therapy of tumors chemotherapy and untoward reaction, in observation group's 36 examples, cancer kind situation is pulmonary carcinoma 25 examples, digestive system cancer 5 examples, other cancer 6 examples; Matched group 19 examples, pulmonary carcinoma 7 examples, digestive system cancer 5 examples, other cancer 7 examples.

Observation group adopts identical embolic chemotherapy with matched group, observation group gives this preparation oral liquid simultaneously, matched group gives high poly-golden Portugal element simultaneously, observes situations such as treatment front and back leukocyte, t lymphocyte subset group, NK cell, hepatic and renal function and chemotherapy side effect etc., observes for 4 weeks.

After 4 weeks of medication, the NK of observation group cell is preceding rising person's 29 row of treatment, and rate of rise is 80.56%; Matched group 10 examples that raise, rate of rise is 52.63%.

Digestive tract side reaction between group in the chemotherapy process, a situation arises for nausea and vomiting etc. relatively:

A situation arises is for nausea and vomiting: 13 examples take place in observation group's nausea and vomiting, and incidence rate is 36.11%: 15 examples take place the matched group nausea and vomiting, and incidence rate is 78.95%; Observation group's digestive tract side reaction obviously is less than matched group;

Conclusion (of pressure testing) is: this preparation is in tumor combined chemotherapy process, and the routine number of leukopenia obviously is less than matched group, and (P＜0.05 points out it that marrow function is had obvious protective effect; Can significantly improve the NK cell activity, show that it can improve the immunity of body under the chemotherapy state; Can alleviate the gastrointestinal reaction due to the chemotherapy to a certain extent, incidence of nausea and vomiting is evident as low than matched group.

Tentative confirmation, this preparation can alleviate the inhibition of chemotherapy to bone marrow, improve patient's immunologic function, alleviate gastral side reaction, make the patient can finish combined chemotherapy smoothly, thereby are the anticancer preventative and valuable Chinese medicine preparation of auxiliary therapy of chemotherapy.

No. 2 Clinic Institute of the Medical University of China has done treatment clinical trial to cancer patient's qi-blood deficiency syndrome with this oral liquid formulations.

The case of being tried that will meet diagnosing tumor and include the case standard in is divided into treatment at random and organizes 21 examples, matched group 21 examples.Sick kind aspect, treatment group pulmonary carcinoma 8 examples, digestive system carcinoma 3 examples, anxious leukemia 3 examples, other cancer 6 examples of drenching slowly: matched group pulmonary carcinoma 5 examples, digestive system carcinoma 4 examples, anxious leukemia 4 examples, other cancer 8 examples of drenching slowly.

This oral liquid formulations of treatment group, matched group medication FUFANG EJIAO JIANG oral liquid.Treatment group produce effects 9 examples, obvious effective rate is 42.86%, effective 10 examples, effective percentage is 47.62%, invalid 2 examples, total effective rate 90.48%; Effective 9 examples of matched group, effective percentage is 42.86%, invalid 12 examples, total effective rate 42.86%.

The result shows: oral liquid has the symptom and sign of tumor post-operation deficiency of both QI and blood under the chemotherapy state to be adjusted and the improvement effect preferably, especially to pale complexion, refreshing particularly remarkable by symptom curative effects such as weak, deficiency of QI with disinclination to talk.Its total effective rate is 90.48%, obviously is better than control drug.Patient's appetite increases, and gastrointestinal side effect alleviates.

Oral liquid and chemotherapy combined administration can improve patients undergoing chemotherapy autoimmune ability, improve CD ₃And CD ₄/ CD ₈Ratio can make patient's leukocyte that to a certain degree rising is arranged, and knowing this preparation thus by inference has the certain protection effect to marrow function, and liver, renal function are had the certain protection effect.Can alleviate or alleviate the toxic and side effects that chemotherapy causes, safe and reliable.

Claims (3)

1, prevent or slow down the preparation of chemotherapy side effect, it is characterized in that it is made by following materials of weight proportions medicine:

Radix Ginseng Rubra 15g-24g Radix Astragali 15g-24g Radix Angelicae Sinensis 6g-12g

Radix Asparagi 15g-24g Fructus Psoraleae 10g-15g Fructus Lycii 9g-15g

Cortex Acanthopancis 6g-10g Radix Salviae Miltiorrhizae 8g-12g Flos Lonicerae 8g-12g

Radix Glycyrrhizae 5g-8g.

2, prevent or slow down the preparation method of the preparation of chemotherapy side effect, its feature in concrete steps is:

1) the 15g-24g red ginseng powder is broken into fine powder, the CO2 supercritical extraction,

2) the 15g-24g Radix Astragali, 6g-12g Radix Angelicae Sinensis, 8g-12g Radix Salviae Miltiorrhizae, 10g-15g Fructus Psoraleae, 6g-10g Cortex Acanthopancis add 80% alcohol reflux secondary, add 8 times of amounts for the first time, extract 2 hours, add 6 times of amounts for the second time, extract 1.5 hours, filter, and get filtrate 1, filtering residue;

3) filtering residue and 15g-24g Radix Asparagi, 9g-15g Fructus Lycii, 8g-12g Flos Lonicerae, 5g-8g Radix Glycyrrhizae decoct with water twice, add 8 times of water gagings for the first time, decoct 2 hours, add 8 times of water gagings for the second time, decoct 1.5 hours, filter, and get filtrate 2;

4) filtrate 1,2 is merged, the relative density that is evaporated to 60 ℃ under is a 1.30-1.32 extractum, extractum and Radix Ginseng Rubra fine powder mixing, 60-70 ℃ time drying, pulverize product.

3, preparation method according to claim 2 is characterized in that product adds dextrin, and mixing adds ethanol and makes granular preparation, gets tablet, powder or capsule by pharmaceutical technology.