CN1698650A - Arsenious acid injection for treating primary carcinoma of liver and preparation method thereof - Google Patents
Arsenious acid injection for treating primary carcinoma of liver and preparation method thereof Download PDFInfo
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- CN1698650A CN1698650A CN 200410042702 CN200410042702A CN1698650A CN 1698650 A CN1698650 A CN 1698650A CN 200410042702 CN200410042702 CN 200410042702 CN 200410042702 A CN200410042702 A CN 200410042702A CN 1698650 A CN1698650 A CN 1698650A
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- 238000002347 injection Methods 0.000 title claims abstract description 44
- 239000007924 injection Substances 0.000 title claims abstract description 44
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Disclosed is an arsenious acid injection for treating primary carcinoma of liver and preparation method, which comprises weighing 10-8000 weight parts of arsenic trioxide, charging into a reactor, charging water for injection 100-500 mass times of arsenic trioxide, heating till boiling, adjusting pH to 8-12 with NaOH, so as to dissolve the arsenic trioxide completely, adjusting the pH to 3-6.5 with hydrochloric acid, cooling down to room temperature, charging water for injection, adjusting pH to 4.5-6.5 with NaOH and hydrochloric acid solvent, charging isotonic substance, finally encapsulating and sterilizing.
Description
Technical field
The present invention relates to a kind of arsenous acid injection and preparation method thereof, this arsenious acid injection can be treated primary hepatocarcinoma, especially the primary hepatocarcinoma middle and advanced stage.
Background technology
Arsenic compound is the naturally occurring material of nature, and it has had for a long time as medicinal application.Wherein, a kind of arsenic compound-arsenic trioxide that people are familiar with very much is commonly called as arsenicum, be a kind of extremely toxic substance, but the arsenic trioxide of pharmacology concentration has excellent curative to leukemia and malignant tumor.Find after deliberation, arsenic trioxide mainly by cell growth inhibiting and tumor neogenetic blood vessels form, inducing cell partly breaks up and inducing cell is transferred performance antitumor actions such as dying.China's magazine " cancer " 2002.21 (12): 1368-1389 " arsenic trioxide study on mechanism progress " (author Feng Chunqiong, beautiful and the Zheng Wenling of Marvin's), " Chinese general surgery magazine " 2202.4 Vol.11 No.4 articles are numbered " the Arsenic Trioxide Induced solid tumor cell is transferred the progress of dying " that " Anticancer Effect and Mechanism of arsenic trioxide " (author Chen Jun is strong, and Li Shao is gloomy) of 1005-6947 (2002) 04-0236-03 and Chinese magazine " Tianjin pharmacy " the 14th volume the 2nd phase article April in 2002 be numbered 1006-5687 (2002) 02-0003-03 and have done clear to above-mentioned mechanism, describe in detail.
Hepatocarcinoma comprises primary hepatocarcinoma and secondary liver cancer (secondary liver cancer).Primary hepatocarcinoma (hereinafter to be referred as hepatocarcinoma) is China's common malignancy, since the onset concealment, middles and advanced stage that belong to when making a definite diagnosis more, therapeutic effect is relatively poor, and prognosis is abominable, is a kind of disease of serious threat people life and health.Mainly come diagnosing liver cancer by detecting alpha-fetoprotein (AFP) clinically, when lasting 4 weeks of AFP＞400 μ g/L, diagnosable usually is hepatocarcinoma.The general hepatocarcinoma clinical stages method of China is, is divided into for three phases according to the clinical manifestation of hepatocarcinoma, that is: I phase, no clear and definite hepatocarcinoma symptom and sign person; The II phase is between I phase and III person between the phase; The III phase, one of jaundice, ascites, metastasis or dyscrasia person is arranged.I phase hepatocarcinoma is early hepatocarcinoma, the excision of performing the operation mostly, and also prognosis is better.II phase hepatocarcinoma is hepatocarcinoma in mid-term, and III phase hepatocarcinoma is advanced liver cancer, and both do not have the indication of excision, and prognosis is also obviously relatively poor.Comprehensive Treatment to hepatocarcinoma mainly is divided into two kinds: first operative treatment is main Comprehensive Treatment, and this is present preferred option.This kind method mainly is applicable to the treatment early hepatocarcinoma.But the just minority that can ectome, for can not by excision hepatocarcinoma in, the advanced liver cancer patient, adopt the Comprehensive Treatment of non-operative treatment, as based on the Comprehensive Treatment of embolism chemical therapeutic, based on the Comprehensive Treatment of local alinjection therapy, based on the Comprehensive Treatment of radiation with based on the Comprehensive Treatment of Chinese medicine.The toxic and side effects of radiation and chemotherapy is very big, and is heavier to other organ injury of patient; Alinjection and Chinese medicine are applicable to the liver cancer patient of different situations respectively.Up to the present, also there is not a kind of treatment primary hepatocarcinoma, especially the specific medicament of constitutional advanced liver cancer.
The patent No. is that 95108768.1 Chinese patent discloses a kind of leukemia, hepatocarcinoma and lymphadenomatous injection, and this injection is arsenic trioxide 1-10 gram and sodium chloride 8 to be restrained be dissolved in 1000 milliliters of waters for injection, boils, filters, sterilizing forms.But its disclosed injection discloses very general, simply treatment hepatocarcinoma, only disclose this injection and can be used for the treatment of hepatocarcinoma, for primary hepatocarcinoma, the treatment details of advanced primary liver cancer especially, as using method, curative effect etc., this patent is not open.
Application number is that 98813016.5 Chinese patent application discloses a kind of preparation method of arsenic trioxide preparation and it is used for the treatment of the method for leukemia, lymphoma and hard tumour.Described preparation method is that highly purified solid-state arsenic trioxide is dissolved in the aqueous solution of pH＞12, is 8-8.5 with the hydrochloric acid residual titration to pH then, and filtration, sterilization, encapsulation form.This patent also only discloses it and has applied for that oxidation two arsenic preparations of protecting can treat a kind of hepatocarcinoma in the hard tumour; equally; this application does not disclose the said preparation treatment fully for primary hepatocarcinoma yet, especially the treatment details of advanced primary liver cancer.
Summary of the invention
Technical problem to be solved by this invention is injection that proposes a kind of arsenious acid and preparation method thereof, and this injection is used for the treatment of primary hepatocarcinoma, especially the primary hepatocarcinoma middle and advanced stage.
Main design of the present invention is based on prior art, improves the preparation technology of arsenous acid injection, proposes a kind of new preparation method, makes a kind of new arsenous acid injection; The inventor finds this injection for primary hepatocarcinoma by a large amount of work, and especially advanced primary liver cancer has excellent curative.
Technical scheme of the present invention is described in further detail below.
Take by weighing 10-8000, preferred 100-2000 weight portion arsenic trioxide, join in the reactor, adding quality then is arsenic trioxide quality 100-500 water for injection doubly, heated and boiled, with NaOH solution adjust pH is 8-12, arsenic trioxide is dissolved fully, is 3-6 with the hydrochloric acid adjust pH then, is cooled to room temperature, adding water for injection to arsenic trioxide weight concentration then is 10/1000000-8/1000, preferred 100/1000000-2/1000, reuse NaOH solution and hydrochloric acid solution adjust pH are 4.5-6.5, potting, sterilization promptly gets arsenous acid injection.When producing high-capacity injection, also can after be 4.5-6.5, adjust pH add to wait and ooze material, as the sodium chloride solution of 0.9% weight or the glucose solution of 5% weight, account for the 0.8-1.0% of medicinal liquid total amount Deng the weight of oozing material, potting again, sterilization produce haemolysis in the time of can preventing to use.
Described arsenic trioxide is a high purity material, and preferably its purity is higher than 99.9%.
During use, amount joins isosmotic solution with this injection as required, in 0.9% sodium chloride solution or 5% glucose solution, gives patient's intravenous drip or intramuscular injection.
Among the present invention, by regulating pH value 8-12, improve the dissolubility of arsenic trioxide, the re-adjustment pH value is to dilute behind the 3-6, makes solute still exist with the arsenious acid form, thereby can not produce the arsenic trioxide precipitation, last regulator solution pH value is 4.5-6.5, make the form stable existence of effective ingredient arsenic trioxide with arsenious acid, avoided the too high medicinal effects problem that influences injection that causes of acidity, the inventor is effective best by the above-mentioned condition of a large amount of evidences; And by regulating pH value, make to send out and answer system stable, regulation and control easily, thus enhance productivity.The inventor obtains following result by test, and using the patent No. is that 95108768.1 disclosed methods prepare arsenic trioxide injection, and preparation process on average took time about 8 hours, and uses the inventive method only to need about 4 hours.As seen, the preparation method that the present invention proposes can shorten the production cycle, makes production efficiency improve 1 times.
The inventor finds this injection to primary hepatocarcinoma by a large amount of clinical positions, and especially the primary hepatocarcinoma middle and advanced stage has excellent curative.
Arsenous acid injection of the present invention has been done clinical trial on tumor center of the entire PLA of Nanjing Aug. 1st hospital, Heilongjiang Prov. Tumour Hospital and first Affiliated Hospital of Dalian Medical Univ and other places, and the result is as follows:
One, the short term effect and the untoward reaction of O﹠A arsenous acid injection treatment primary hepatocarcinoma
1. test unit: tumor center of the entire PLA of Nanjing Aug. 1st hospital
2. test method: select 23 routine advanced primary liver cancer patients, 7-8mg/m is got in the arsenic trioxide injection treatment of only using the present invention to propose
2(surface, down together) this injection adds normal saline or 5% Glucose Liquid 500mL, and intravenous drip 3-4 hour, 1 time/day, treated continuously 14 days, intermittently 7-14 days, be one-period.Contact treatment is estimated after 2 cycles, for the state of an illness alleviate fully, part is alleviated, little effect and unconverted patient continue treatment, can not tolerate or disease progression up to patient, can drug withdrawal for disease progression in the therapeutic process.
3. case is selected
Inclusion criteria
(1) histopathology or cytolgical examination turn out to be Patients with Primary; To not obtaining pathology according to the person, need there be iconography+AFP to check, meet the unified clinical diagnosis standard in the whole nation;
(2) primary hepatocarcinoma patient that can't perform the operation:
(3) to observing the patient that focus or metastasis are not carried out chemotherapy (comprising the Hepatic artery intervention) and radiotherapy;
(4) have and to measure and valuable objective observation index;
(5) age was at 18 years old-65 years old;
(6) KPS (pressing medical statistics, down together) scoring is 〉=50 minutes;
(7) estimate life cycle 〉=3 month;
(8) cardiac function, liver function, kidney merit and hemogram are normal substantially before the treatment;
(9) obtain patient's informed consent;
(10) follow up a case by regular visits to possibility.
Exclusion standard
(1) gestation and nursing women;
(2) to the arsenic preparation allergy sufferers;
(3) be the patient of other antineoplastons in January;
(4) heart, liver, renal insufficiency;
(5) serious dermatosis patient;
(6) merging vertigo moves;
(7) patient of ascites is arranged;
(8) serious maincenter and peripheral nervous patient.
Reject the standard of case during evaluation
(1) do not go into group and finish therapist by the selected standard research approach that continues;
(2) be associated with hepatic arterial infusion embolism chemical therapeutic or radiotherapy person simultaneously;
(3) can not finish treatment, death or refusal of treatment by patient person midway because of serious toxicity.
4. therapeutic evaluation standard
(1) objective curative effect:, be divided into: alleviate (CR), part alleviation (PR), little effect (MR), no change (NC) and progress (PD) fully according to the recent objective efficacy assessment standard of WHO solid tumor (1981).
(2) quality of life: according to Karnofsky (KPS) scoring assessment, be improvement, reduce by 〉=10 fens persons and be decline that it is stable changing≤10 fens persons to treat the back than increasing 〉=10 fens persons before treating.
5. toxicity evaluation
Acute and subacute toxicity performance and grade scale (1981) thereof carry out observed and recorded and judgement according to WHO and NCI anticarcinogen.
6. physical data
This group is inpatient.Go into group 23 examples, male's 18 examples wherein, women's 5 examples, 29 years old-68 years old age, The median age 57 years old.9 examples are diagnosed as primary hepatocellular carcinoma (hcc) according to histopathology and/or cytodiagnosis foundation, and 14 examples meet the clinical diagnosis standard of domestic unified regulation by imaging examinations such as clinical medical history, AFP and CT.When going into to organize by domestic unified clinical stages: II phases 13 example, III phases 10 example wherein merges lung transferase 45 example, (skeleton and sub-dermal soft tissue shift) 1 example that shifts with other positions; Heterogenous liver is transplanted the back recurrence and lung shifts 1 example.
7. observation item
(1) selected preceding acquisition and recording medical history, body weight, height, body surface area in detail:
(2) before and after the treatment, check breast and anterioposterior and lateral film, abdominal part (chest in case of necessity) CT, B ultrasonic, electrocardiogram;
(3) lab testing: hemogram, hepatic and renal function; Tumor marker: CEA, AFP etc.;
(4) itemized record and fill in " case report form ";
(5) estimating short term effect and recording start treats to lesion growth time (TTP).
8. result of the test
(1) curative effect:
Go into group 23 examples, do not finish and treat out group 2 examples, valuable is 21 examples: wherein, finish 1 cycle therapy person, 3 examples, 〉=2 cycles 18 examples comprise 2 cycles 12 examples, 3 cycles 4 examples, 5 cycle 1 examples, 6 cycle 1 examples, average 2.38 cycles of administration.
The treatment post-evaluation, PR 2 examples in 21 examples, MR I example, NC 13 examples, PD 5 examples, objective effective percentage (CR+PR) 9.5%, patient's yield (CR+PR+NC) 76.2%.
Go out 2 examples of group, 1 example was at the 8th day of medication, and the state of an illness is obviously made progress, and the patient refuses to continue to use; 1 example is stopped using because of carrying out property oliguria appears in medication after 4 days.
(2) quality of life and doing well,improving:
Mark from KPS, treatment back 20 fens person's 1 examples that rise, 10 fens person's 3 examples, no change person 15 examples, 10 fens person's 1 examples that descend, 20 fens person's 1 examples, quality of life rate of descent only 9.5%.
The cardinal symptom of treatment back Most patients is obviously improved.Merge hepatic region and low-back pain person's 13 examples, treatment back 6 routine pain are improved (46.2%), wherein significantly alleviate 4 examples, total pain relief 2 examples; Other has 4 routine cancer fever treatment back heatings to disappear, and 1 routine singultus disappears, and 1 routine night sweat obviously alleviates.
(3) toxicity:
Carry out 23 examples that have of toxicity evaluation, mainly show as gastrointestinal reaction, 6 examples (26.1%) of wherein feeling sick are vomitted 1 example (4.3%), inappetence 9 examples (39.1%), abdominal distention 5 examples (21.7%); Next is a haematics toxicity, and wherein hemoglobin reduces by 7 examples (30.4%), leukopenia 6 examples (26.1%), thrombocytopenia 5 examples (21.7%); Abnormal liver function 8 examples (34.8%) are arranged.Above-mentioned toxicity mostly is I～II degree greatly, all can disappear or take a turn for the better after anti symptom treatment, does not influence the continuation medication, and is reversible after the drug withdrawal.The death of Quan Zuwu treatment dependency.See following table for details.
The toxicity of arsenic trioxide injection treatment primary hepatocarcinoma
| Toxicity | NCI toxicity (example, %) |
| 0 degree I degree II degree III degree IV degree | |
| Digestion is nausea and vomiting inappetence abdominal distention diarrhoea | ? ??17(73.9)??6(26.1)???0???????0?????????0 ??22(95.7)??1(4.3)????0???????0?????????0 ??14(60.9)??6(26.1)???3(13.0)?0?????????0 ??18(78.3)??3(13.0)???2(8.7)??0?????????0 ??22(95.7)??1(4.3)????0???????0?????????0 |
| The dry pigmentation erythra of skin change | ? ??18(78.3)??5(21.7)???0???????0?????????0 ??23(100)???0?????????0???????0?????????0 ??21(91.3)??0?????????2(8.7)??0?????????0 |
| Drug fever | ??21(91.3)??2(8.7)????0???????0?????????0 |
| Headache | ??23(100)???0?????????0???????0?????????0 |
| Peripheral neuritis | ??19(82.6)??4(17.4)???0???????0?????????0 |
| The hematology changes erythrocyte leukocyte platelet | ? ??16(69.6)??4(17.4)??2(8.7)???1(4.3)????0 ??17(73.9)??2(8.7)???2(8.7)???2(8.7)????0 ??18(78.3)??4(17.4)??1(4.3)???0?????????0 |
| Liver function glutamate pyruvate transaminase glutamic oxaloacetic transaminase, GOT | ? ??17(73.9)??4(17.4)??2(8.7)???0?????????0 ??15(65.2)??4(17.4)??4(17.4)??0?????????0 |
| Renal function blood urea nitrogen creatinine | ? ??22(95.7)??1(4.3)???0????????0?????????0 ??23(100)???0????????0????????0?????????0 |
| The ECG change myocardial ischemia | ? ??21(91.3)??1(4.3)???1(4.3)???0?????????0 |
Two, the short term effect and the untoward reaction of O﹠A arsenic trioxide injection treatment primary hepatocarcinoma
1. test unit: Heilongjiang Prov. Tumour Hospital
2. test method is the same
3. case is selected the same
4. therapeutic evaluation standard is the same
5. toxicity is estimated the same
6. physical data
21 examples are inpatient, male 18 examples, and women 3 examples, the man: the woman is 6: 1, age 37-66 year, The median age 54 years old.1 example is made a definite diagnosis through histocytology in 21 examples, and 20 examples of surplusing all are diagnosed as primary hepatocarcinoma through iconography and AFP.This 21 example is just controls the patient, II phases 13 examples (61.9%) wherein, III phases 8 examples (38.1%).
7. observation item is the same
8. result of the test
(1) objective curative effect: 1 example man trouble can not be carried out therapeutic evaluation because of treatment two cycles of less than in 21 examples.Can estimate PR 2 examples (10%) in 20 examples of curative effect, NC 12 examples (60%), PD6 example (30%).Effective percentage 10%, yield (PR+NC) is 70% (14/20).
(2) quality of life and clinical symptoms are improved: KPS observes 3 examples that show that treatment back integration rose＞10 fens, improvement rate 15%, wherein 2 routine KPS rose 15 stable examples, coefficient of stabilization 75%＞20 fens, 2 examples descend, each 1 example of＞10 minutes and＞20 minutes, quality of life rate of descent be 10%, right season rib and the lumbago and backache treatment before be 16 examples, treatment back 12 examples alleviate (75%), wherein 3 routine total pain reliefs (18.8%).
(3) toxicity: clinical observation arsenic trioxide injection toxicity is light, is mainly digestive tract (feeling sick or inappetence), secondly for liver function changes, xerosis cutis.More rare is (seeing the following form) such as headache, drug fevers.
| Toxicity | NCI toxicity (example, %) |
| 0 degree I degree II degree III degree IV degree | |
| Digestion is nausea and vomiting inappetence abdominal distention diarrhoea | ? ??11(52.4)?7(33.3)3(14.3)0?????0 ??18(85.7)?3(14.3)?0?????0?????0 ??15(71.4)?6(28.6)?0?????0?????0 ??17(80.9)?2(9.5)??2(8.7)0?????0 ??21(100)??0???????0?????0?????0 |
| The dry pigmentation erythra of skin change | ? ??15(71.4)?6(28.6)?0?????0?????0 ??21(100)??0???????0?????0?????0 ??21(100)??0???????0?????0?????0 |
| Drug fever | ??18(85.7)?3(14.3)?0?????0?????0 |
| Headache | ??17(80.9)?4(19.1)?0?????0?????0 |
| Peripheral neuritis | ??21(100)??0???????0?????0?????0 |
| The hematology changes erythrocyte leukocyte platelet | ? ??18(85.7)?1(4.8)??2(9.5)0?????0 ??18(85.7)?3(14.3)?0?????0?????0 ??19(90.5)?2(9.5)??0?????0?????0 |
| Liver function glutamate pyruvate transaminase glutamic oxaloacetic transaminase, GOT | ? ??17(80.9)?4(19.1)?0?????0?????0 ??14(66.7)?7(33.34)0?????0?????0 |
| Renal function blood urea nitrogen creatinine | ? ??20(95.2)?1(4.8)??0?????0?????0 ??20(95.2)?1(4.8)??0?????0?????0 |
| The ECG change myocardial ischemia | ? ??20(95.2)?1(4.8)??0?????0?????0 |
From The above results as can be seen, the injection that uses the present invention's proposition is to the advanced primary liver cancer patient treatment, can effectively stablize the state of an illness, improve patients ' life quality, and can significantly alleviate hepatic region and low-back pain, has excellent curative, and this poison of drug side reaction is lighter and reversible, and patient easily accepts.
The specific embodiment
Embodiment 1
Take by weighing 1000mg purity and be 99.99% arsenic trioxide, join in the reactor, adding quality is the water for injection of 300 times of arsenic trioxide quality, heated and boiled, with NaOH solution adjust pH is 11, arsenic trioxide is dissolved fully, with the hydrochloric acid adjust pH is 4, be cooled to room temperature, adding water for injection to arsenic trioxide weight concentration then is 1/1000, and reuse NaOH solution and hydrochloric acid solution adjust pH are 5.5, the sodium chloride solution 8.5g that adds 0.9% weight then, potting, sterilization promptly gets arsenous acid injection.
Embodiment 2
Take by weighing 10mg purity and be 99.99% arsenic trioxide, join in the reactor, adding quality is the water for injection of 400 times of arsenic trioxide quality, heated and boiled, with NaOH solution adjust pH is 10, and arsenic trioxide is dissolved fully, is 5 with the hydrochloric acid adjust pH, be cooled to room temperature, adding water for injection to arsenic trioxide weight concentration then is 100/1000000, and reuse NaOH solution and hydrochloric acid solution adjust pH are 6, potting, sterilization promptly gets arsenous acid injection.
Embodiment 3
Take by weighing 5000mg purity and be 99.99% arsenic trioxide, join in the reactor, adding quality is the water for injection of 200 times of arsenic trioxide quality, heated and boiled, with NaOH solution adjust pH is 9, arsenic trioxide is dissolved fully, with the hydrochloric acid adjust pH is 3, be cooled to room temperature, adding water for injection to arsenic trioxide weight concentration then is 5/1000, and reuse NaOH solution and hydrochloric acid solution adjust pH are 5, the glucose solution 9.5g that adds 5% weight then, potting, sterilization promptly gets arsenous acid injection.
Model case
Korea Spro * *, the man, 35 years old, because of upper right abdomen discomfort with the dry cough first quarter moon about, in December in 2000 12 days at Nanjing Aug. 1st hospital admission.The multiple occupy-place of two lung is down shown in the occupy-place of imaging examination CT prompting right lobe of liver, rabat, in conjunction with the HBsAg positive, AFP＞400 μ g/L, is diagnosed as the primary hepatocarcinoma III phase.December was gone into group on the 15th in 2000, and December in 2000 played examination on the 26th and gives 20 days (total amount 280mg) of arsenous acid injection treatment of the present invention, and process is smooth, and slight night sweat is only arranged in the patient treatment, and treatment back leukocyte worker degree descends, and does not have other discomforts.CT shows liver occupy-place 8.3cm * 5.7cm before the treatment, and the check of treatment back before dwindles 54.1% for 5.3cm * 4.1cm, and the state of an illness obtains part to be alleviated, and reexamine focus is 4.6cm * 3.9cm after January, still is in the relieved state.The back patient institute that do not come in time continues treatment, uses instead in the outer court voluntarily strongly to select the scheme chemotherapy with PDD, and the state of an illness is made progress on the contrary, and existing a large amount of ascites are invalid through active treatment when being admitted to hospital once more at the beginning of 5 months calendar year 2001s, and 26 die from the hepatocarcinoma liver failure May calendar year 2001.
The king * *, the man, 64 years old, because of the uncomfortable first quarter moon of upper right abdomen dull pain surplus, on October 28th, 1998 CT examination find: the occupy-place of right lobe of liver massive type, the HBsAg positive, AFP＜20 μ g/L through the cytolgical examination of fine needle liver puncture, is diagnosed as the primary hepatoma II phase.Use the treatment of Mifurol Tab associating cinobufacin to December 23 twice-daily interventional therapys instead because of more serious post embolizatiou syndrome occurring November 6 the same year, and the state of an illness is slowly made progress.Check on March 4th, 1999 CT shows right lobe of liver focus 15cm * 13cm, the upper right abdomen pain of patient obviously, poor appetite, weak companion's skin blackout, be unwilling to continue chemotherapy, use arsenous acid injection of the present invention on March 12nd, 1999 and treat one-period, process is smooth, stomachache, weak symptom and skin blackout obviously alleviate after the medication, and appetite takes a turn for the better.Gave the 2nd cycle therapy again on April 15th, 1999, treatment back check CT shows right lobe of liver focus 11.0cm * 8.5cm, calculates liver lesion and dwindles 52.1% before than medication, and the state of an illness obtains part and alleviates.Patient's right hypochondrial region disappears, and the KPS scoring was risen to 90 fens by treatment in preceding 70 minutes.Check CT once more after the medication of the 3rd cycle finishes and show right lobe of liver focus 9.5cm * 8.6cm, still be in the part relieved state.In January, 2002 state of an illness repeatedly, it was invalid to use low dosage 5-Fu persistent intravenous injection instead, in death on February 17 in 2002.Survived after making a definite diagnosis in April, 4.
In * *, the man 66 years old, goes into Heilongjiang Prov. Tumour Hospital October 15 calendar year 2001.This suffered from abdominal pain 3 months, and is invalid through multi-treatment, and after CT is diagnosed as primary hepatocarcinoma, the focus size is about 44.0 * 54.7mm
2, the AFP value is normal, and patient's physically-draining is become thin.Begin to use arsenous acid injection treatment of the present invention, an intravenous drip of 10mg, logotype 31 days, accumulated dose 310mg October 19 calendar year 2001, therapeutic process is comparatively smooth, obvious adverse reaction do not occur, and only leukocyte slightly descends, but symptom is alleviated gradually, and stomachache alleviates, and appetite is cumulative.Treatment back upper abdominal pain disappears substantially, check CT, and focus is reduced into 25.7 * 29.1mm
2, the state of an illness obtains part and alleviates.20 patients of calendar year 2001 December are through check, and focus size no change has no adverse reaction.This patient is survived so far.
Poplar * *, the man, 65 years old, Augusts 15 in 2000, Nikkei MPI and CT were diagnosed as primary hepatocarcinoma, liver caudal lobe focus 4.5cm * 6.5cm, abdominal distention is serious, have an effect, KPS scoring 80 is respectively on November 9,12 days to 2000 October in 2000 and December 23 days to 2000 November in 2000 use on the 21st arsenous acid injection intravenous drip treatment of the present invention, each 10mg, once a day, accumulated dose is 280mg.After the treatment, focus is 2.2cm * 2.2cm, slight abdominal distention, weak, and KPS scoring 80, untoward reaction has slight gastrointestinal reaction, peripheral neuritis and skin change.The state of an illness is alleviated 6 months.This patient was admitted to hospital once more July 10 calendar year 2001, and tumor takes place to shift in the liver, and is dead after 2 months.
The king * *, man 64 years old, detect through CT and cytology and be diagnosed as primary hepatocarcinoma in October, 1997, and liver occupy-place 15cm * 13cm is unable, become thin, the uncomfortable KPS scoring 70 of upper right abdomen dull pain, respectively at March in 1999 on March 31st, 1 1999 on the 12nd and April 15 in 1999 saying on May 5th, 1 1999, use arsenous acid injection intravenous drip treatment of the present invention, each 15mg, once a day, accumulated dose is respectively 300mg and 315mg.Treatment back liver occupy-place 11.0cm * 8.5cm, uncomfortable basic disappearance of upper right abdomen dull pain, untoward reaction is that erythrocyte, platelet and liver function have the II level to change, KPS scoring 90, the state of an illness obtains part and alleviates.Treatment back survival 2 years 10 months.
Claims (7)
1, a kind of arsenous acid injection for the treatment of primary hepatocarcinoma, it is characterized in that, this injection contains the arsenious acid aqueous solution, and arsenious acid content is wherein amounted to into the 10/1000000-8/1000 that arsenic trioxide weight accounts for the injection gross weight, and the pH value of this injection is 4.5-6.5.
2, arsenous acid injection as claimed in claim 1 is characterized in that, arsenious acid content is amounted to into the 100/1000000-2/1000 that arsenic trioxide weight accounts for the injection gross weight.
3, a kind of preparation method as claim 1 arsenous acid injection is characterized in that, this method may further comprise the steps:
Take by weighing 10-8000 weight portion arsenic trioxide, join in the reactor, adding quality is arsenic trioxide 100-500 water for injection doubly, heated and boiled, with NaOH solution adjust pH is 8-12, and arsenic trioxide is dissolved fully, is 3-6 with the hydrochloric acid adjust pH, be cooled to room temperature, adding water for injection to arsenic trioxide weight concentration then is 10/1000000-8/1000, and reuse NaOH solution and hydrochloric acid solution adjust pH are 4.5-6.5, potting, sterilization promptly gets arsenous acid injection.
4, the preparation method of arsenous acid injection as claimed in claim 3 is characterized in that, described be 4.5-6.5 with NaOH solution and hydrochloric acid solution adjust pH after, add to wait and to ooze material, its weight is the 0.8-1.0% of medicinal liquid gross weight, potting then, sterilization.
5, the preparation method of arsenous acid injection as claimed in claim 4 is characterized in that, described grade is oozed the sodium chloride solution that material is 0.9% weight or the glucose solution of 5% weight.
6, the application of arsenous acid injection as claimed in claim 1 in the medicine of preparation treatment primary hepatocarcinoma.
7, the application of arsenous acid injection as claimed in claim 1 in the medicine of preparation treatment advanced primary liver cancer.
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| CN102989011A (en) * | 2012-12-06 | 2013-03-27 | 哈尔滨医科大学 | Medicine composition for treating liver caner and application thereof |
| WO2013082875A1 (en) * | 2011-12-07 | 2013-06-13 | 浙江中医药大学 | Arsenic compound solution and albumin nanoparticle and lyophilized preparation entrapping arsenic compound prepared using same |
| CN103393719A (en) * | 2013-08-07 | 2013-11-20 | 刘怀振 | Production method of arsenic trioxide oral liquid |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2013082875A1 (en) * | 2011-12-07 | 2013-06-13 | 浙江中医药大学 | Arsenic compound solution and albumin nanoparticle and lyophilized preparation entrapping arsenic compound prepared using same |
| US9271943B2 (en) | 2011-12-07 | 2016-03-01 | Zhejiang Chinese Medical University | Arsenic compound solution and albumin nanoparticle and lyophilized preparation entrapping arsenic compound prepared using same |
| CN102989011A (en) * | 2012-12-06 | 2013-03-27 | 哈尔滨医科大学 | Medicine composition for treating liver caner and application thereof |
| CN103393719A (en) * | 2013-08-07 | 2013-11-20 | 刘怀振 | Production method of arsenic trioxide oral liquid |
| CN103393719B (en) * | 2013-08-07 | 2014-07-23 | 骆红宇 | Production method of arsenic trioxide oral liquid |
| US10111836B2 (en) | 2015-02-01 | 2018-10-30 | Orsenix Holdings Bv | High surface-area lyophilized compositions comprising arsenic for oral administration in patients |
| US10272045B2 (en) | 2015-02-01 | 2019-04-30 | Orsenix Holdings Bv | High surface-area lyophilized compositions comprising arsenic for oral administration in patients |
| US10653628B2 (en) | 2015-02-01 | 2020-05-19 | Orsenix Holdings Bv | High surface-area lyophilized compositions comprising arsenic for oral administration in patients |
| US12364664B2 (en) | 2015-02-01 | 2025-07-22 | Quetzal Therapeutics, Llc | Lyophilized compositions comprising arsenic |
| CN108261422A (en) * | 2018-01-09 | 2018-07-10 | 广西大学 | A kind of drug for inhibiting tumor cell proliferation |
| CN108670977A (en) * | 2018-07-23 | 2018-10-19 | 广西大学 | A kind of drug inhibiting tumor cell proliferation |
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