CN115154423B - Ibandronate sodium injection and preparation method thereof - Google Patents
Ibandronate sodium injection and preparation method thereof Download PDFInfo
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- CN115154423B CN115154423B CN202210936030.8A CN202210936030A CN115154423B CN 115154423 B CN115154423 B CN 115154423B CN 202210936030 A CN202210936030 A CN 202210936030A CN 115154423 B CN115154423 B CN 115154423B
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- ibandronate sodium
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- 238000002347 injection Methods 0.000 title claims abstract description 41
- 239000007924 injection Substances 0.000 title claims abstract description 41
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 229960005236 ibandronic acid Drugs 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 239000003549 soybean oil Substances 0.000 claims abstract description 24
- 235000012424 soybean oil Nutrition 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000008215 water for injection Substances 0.000 claims abstract description 16
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims abstract description 14
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 14
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 14
- 239000003921 oil Substances 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 4
- 238000003756 stirring Methods 0.000 claims description 32
- 238000010438 heat treatment Methods 0.000 claims description 15
- 238000005303 weighing Methods 0.000 claims description 11
- 239000007788 liquid Substances 0.000 claims description 10
- 235000019198 oils Nutrition 0.000 claims description 7
- 238000007920 subcutaneous administration Methods 0.000 claims description 7
- 239000003708 ampul Substances 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 6
- 230000001954 sterilising effect Effects 0.000 claims description 6
- 229940015872 ibandronate Drugs 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 230000007794 irritation Effects 0.000 abstract description 13
- 238000010254 subcutaneous injection Methods 0.000 abstract description 8
- 239000007929 subcutaneous injection Substances 0.000 abstract description 8
- 239000012071 phase Substances 0.000 description 26
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 2
- 206010040880 Skin irritation Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000036556 skin irritation Effects 0.000 description 2
- 231100000475 skin irritation Toxicity 0.000 description 2
- 231100000430 skin reaction Toxicity 0.000 description 2
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010060891 General symptom Diseases 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Dispersion Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an ibandronate sodium injection and a preparation method thereof, wherein the injection is a water-in-oil injection composed of ibandronate sodium, water, soybean oil, span 80 and tween 80, and is characterized in that: the ratio of soybean oil to water for injection is 3.0:1-4.0:1, the content of span 80 is 4.0-6.0%, and the content of tween 80 is 0.7-1.0%, both in weight percent. Compared with the prior art, the method remarkably reduces the irritation of subcutaneous injection of the ibandronate sodium.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a water-in-oil ibandronate sodium injection and a preparation method thereof.
Background
The ibandronate sodium injection is a third generation bisphosphonate medicament, and is mainly used for treating postmenopausal osteoporosis, preventing bone related events of patients suffering from breast cancer bone metastasis, and treating hypercalcemia caused by malignant tumors with or without bone metastasis. However, the currently marketed ibandronate sodium injection has strong irritation during injection, so slow drip transfusion is required, and the one-time administration time is up to 2 hours. Not only the administration time is long, but also the irritation side effects such as pain still exist. Causing severe discomfort and poor compliance to the patient.
In order to solve the defects of the existing ibandronate sodium injection, a novel water-in-oil ibandronate sodium injection is provided.
Disclosure of Invention
The invention aims to provide an ibandronate sodium injection and a preparation method thereof, wherein the injection is a water-in-oil injection, and can remarkably reduce the irritation of ibandronate sodium, especially the irritation during subcutaneous injection.
To achieve the object of the present invention, the following embodiments are provided:
the invention discloses an ibandronate sodium injection, which is a water-in-oil injection composed of ibandronate sodium, water, soybean oil, span 80 and tween 80, and is characterized in that: the ratio of soybean oil to water for injection is 3.0:1-4.0:1, the content of span 80 is 4.0-6.0%, and the content of tween 80 is 0.7-1.0%.
Preferably, in the injection of the present invention, the ratio of soybean oil to water for injection is 3.4:1, the content of span 80 is 5.5%, and the content of tween 80 is 0.9%.
Preferably, in the injection of the present invention, the weight ratio of ibandronate sodium to soybean oil is 1:164-1:188, preferably 1:170.
the invention also provides a preparation method of the injection, which comprises the following steps:
1) Weighing the water for injection with the prescription amount, placing the water for injection in a liquid preparation container 1, adding the ibandronate with the prescription amount, and stirring and dissolving completely to obtain a phase A;
2) Weighing soybean oil with a prescription amount, placing the soybean oil into a liquid preparation container 2, adding span 80 and tween 80 with the prescription amount, and stirring and dissolving completely to obtain phase B;
3) Heating the phase A and the phase B to 70+/-3 ℃, adding the water phase to the oil phase under the conditions of stirring speed of 300-500r/min and heating maintaining temperature of 70+/-3 ℃, stirring for 0.5 hour, stopping heating, continuously stirring for 1 hour under the conditions of stirring speed of 100-200r/min, and filtering;
4) Filling the filtrate obtained in the step 3) into ampoule bottles, and sterilizing to obtain the product.
The ibandronate sodium injection of the present invention may be used for intravenous administration and subcutaneous administration, preferably subcutaneous administration.
The ibandronate sodium injection is prepared by dissolving ibandronate sodium in water for injection to obtain an aqueous phase containing ibandronate sodium, dissolving span 80 and tween 80 in soybean oil to obtain an oil phase containing soybean oil, adding the aqueous phase containing ibandronate sodium into the oil phase containing soybean oil under stirring, and emulsifying. Compared with the prior art, the method remarkably reduces the irritation of subcutaneous injection of the ibandronate sodium. Can improve the safety of injection and the compliance of patients.
Detailed Description
The essence of the invention will be better understood by the following examples. The following examples are provided to illustrate and understand the spirit of the present invention, but should not be construed as limiting the scope of the invention.
Example 1
Prescription:
the preparation process comprises the following steps:
1) Weighing the water for injection with the prescription amount, placing the water for injection in a liquid preparation container 1, adding the ibandronate with the prescription amount, and stirring and dissolving completely to obtain a phase A;
2) Weighing soybean oil with a prescription amount, placing the soybean oil into a liquid preparation container 2, adding span 80 and tween 80 with the prescription amount, and stirring and dissolving completely to obtain phase B;
3) Heating the phase A and the phase B to 70+/-3 ℃, adding the water phase to the oil phase under the conditions of stirring speed of 300-500r/min and heating maintaining temperature of 70+/-3 ℃, stirring for 0.5 hour, stopping heating, continuously stirring for 1 hour under the conditions of stirring speed of 100-200r/min, and filtering;
4) Filling the filtrate obtained in the step 3) into ampoule bottles, and sterilizing to obtain the product.
Example 2
Prescription:
the preparation process comprises the following steps:
1) Weighing the water for injection with the prescription amount, placing the water for injection in a liquid preparation container 1, adding the ibandronate with the prescription amount, and stirring and dissolving completely to obtain a phase A;
2) Weighing soybean oil with a prescription amount, placing the soybean oil into a liquid preparation container 2, adding span 80 and tween 80 with the prescription amount, and stirring and dissolving completely to obtain phase B;
3) Heating the phase A and the phase B to 70+/-3 ℃, adding the water phase to the oil phase under the conditions of stirring speed of 300-500r/min and heating maintaining temperature of 70+/-3 ℃, stirring for 0.5 hour, stopping heating, continuously stirring for 1 hour under the conditions of stirring speed of 100-200r/min, and filtering;
4) Filling the filtrate obtained in the step 3) into ampoule bottles, and sterilizing to obtain the product.
Example 3
Prescription:
the preparation process comprises the following steps:
1) Weighing the water for injection with the prescription amount, placing the water for injection in a liquid preparation container 1, adding the ibandronate with the prescription amount, and stirring and dissolving completely to obtain a phase A;
2) Weighing soybean oil with a prescription amount, placing the soybean oil into a liquid preparation container 2, adding span 80 and tween 80 with the prescription amount, and stirring and dissolving completely to obtain phase B;
3) Heating the phase A and the phase B to 70+/-3 ℃, adding the water phase to the oil phase under the conditions of stirring speed of 300-500r/min and heating maintaining temperature of 70+/-3 ℃, stirring for 0.5 hour, stopping heating, continuously stirring for 1 hour under the conditions of stirring speed of 100-200r/min, and filtering;
4) Filling the filtrate obtained in the step 3) into ampoule bottles, and sterilizing to obtain the product.
Example 4 animal irritation experiments
According to the technical guidelines of Chinese medicine irritation, allergy and hemolysis research, the ibandronate sodium injection is subjected to an irritation test, an experimental animal is a rabbit, a test group (the ibandronate sodium injection of the invention, examples 1-3 and the injection of example 3 are represented), a positive control group (selected reference preparation, bang Luo Li (Bondronate) 2ml:2 mg), a raw material group and a blank group (normal saline) are arranged. The dosage of the product to be used for clinical application is 4mg once, subcutaneous injection, and the highest dosage of single use is 0.067mg/kg (calculated by weight of 60kg per adult). The reference formulation, the raw material set and the example 3 set of this test were administered subcutaneously back-injection at a dose of 1.2mg/kg.
Grouping and administration
9 rabbits were divided into 3 groups, and a homozygote left and right side self-comparison method was used. The number and dosing regimen of each group of animals are shown in the following table:
preparing raw material group samples:
prescription: ibandronate sodium 2.000g
498.000g of physiological saline
Made into 1000 pieces
The preparation process comprises the following steps:
weighing normal saline with a prescription amount, adding ibandronate sodium with the prescription amount, stirring and dissolving completely, filtering, filling the filtrate into ampoule bottles, and sterilizing.
Experimental observation
(1) General condition observation of rabbits
The general symptoms of rabbits were observed before and 6, 24, 48 and 72 hours after the administration. The content includes central and motor nervous system, autonomic nervous system, respiratory system, cardiovascular system, digestive system, genitourinary system, skin and fur, eye, etc.
(2) Subcutaneous irritation symptom observation
The animals were observed for a fizzy and evasive pain response during and after the injection and for thickening at the injection site.
The injection sites were visually observed before and 24, 48 and 72 hours after the administration, the reactions at the subcutaneous injection sites were scored with reference to skin irritation response evaluation criteria, and the irritation intensity of the subcutaneous injections was evaluated with reference to skin irritation intensity classification criteria. Skin response scoring criteria are shown in Table 1, subcutaneous injection stimulation intensity grading criteria are shown in Table 2, and experimental results are shown in Table 3.
TABLE 1 scoring criteria for skin reactions
TABLE 2 subcutaneous irritation intensity grading criteria
Table 3 subcutaneous irritation test results for ibandronate sodium injection administration
The results in Table 3 show that the ibandronate sodium injection of the invention adopts water-in-oil type, has very good safety compared with the existing injection on the market, can realize subcutaneous injection, shortens injection time and can improve patient compliance.
Any simple modification and variation substantially within the spirit of the present invention is also within the scope of the present invention.
Claims (7)
1. The ibandronate sodium injection consists of ibandronate sodium, water, soybean oil, span 80 and Tween 80, and is characterized in that: the ratio of soybean oil to water for injection is 3.0:1-4.0:1, the content of span 80 is 4.0-6.0%, the content of tween 80 is 0.7-1.0%, and the weight ratio of ibandronate sodium to soybean oil is 1:164-1:178, said injection being prepared by a process comprising the steps of:
1) Weighing the water for injection with the prescription amount, placing the water for injection in a liquid preparation container 1, adding the ibandronate with the prescription amount, and stirring and dissolving completely to obtain a phase A;
2) Weighing soybean oil with a prescription amount, placing the soybean oil into a liquid preparation container 2, adding span 80 and tween 80 with the prescription amount, and stirring and dissolving completely to obtain phase B;
3) Heating the phase A and the phase B to 70+/-3 ℃, adding the water phase to the oil phase under the conditions of stirring speed of 300-500r/min and heating maintaining temperature of 70+/-3 ℃, stirring for 0.5 hour, stopping heating, continuously stirring for 1 hour under the conditions of stirring speed of 100-200r/min, and filtering;
4) Filling the filtrate obtained in the step 3) into ampoule bottles, and sterilizing to obtain the product.
2. The injection of claim 1, wherein the ratio of soybean oil to water for injection is 3.4:1.
3. The injection as claimed in claim 1, wherein the span 80 is 5.5%.
4. The injection according to claim 1, wherein the tween 80 is present in an amount of 0.9%.
5. The injection as claimed in claim 1, wherein the weight ratio of ibandronate sodium to soybean oil is 1:170.
6. the injection according to any one of claims 1-5 for intravenous or subcutaneous administration.
7. The injection according to claim 6 for subcutaneous administration.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210936030.8A CN115154423B (en) | 2022-08-05 | 2022-08-05 | Ibandronate sodium injection and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210936030.8A CN115154423B (en) | 2022-08-05 | 2022-08-05 | Ibandronate sodium injection and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115154423A CN115154423A (en) | 2022-10-11 |
| CN115154423B true CN115154423B (en) | 2024-02-23 |
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| CN202210936030.8A Active CN115154423B (en) | 2022-08-05 | 2022-08-05 | Ibandronate sodium injection and preparation method thereof |
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Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2128166A1 (en) * | 2008-05-20 | 2009-12-02 | Chemo Ibérica, S.A. | Polymorphic forms of Ibandronate sodium and processes for preparation thereof |
| IT1396937B1 (en) * | 2009-11-26 | 2012-12-20 | Bruzzese | FORMULATIONS OF BISPHOSPHONATES AND VITAMIN D SUITABLE FOR INTERMITTENT ADMINISTRATION BY INTRAMUSCULAR AND SUBCUTANEOUS |
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2022
- 2022-08-05 CN CN202210936030.8A patent/CN115154423B/en active Active
Non-Patent Citations (3)
| Title |
|---|
| Site-Specific human breast cancer (MDA-MB-231) metastases in nude rats:model characterisation and in vivo effects of ibandronate on tumour growth;Marcus neudret et al.;《Int. J. Cancer》;第107卷;第468–477页 * |
| 张天胜 等.《表面活性剂应用技术》.化学工业出版社,2001,(第1版),第148页. * |
| 胡容峰 等.《工业药剂学》.中国中医药出版社,2010,(第1版),第397页. * |
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