WO2020186963A1 - 一种草乌甲素g晶型及其制备方法与应用 - Google Patents

一种草乌甲素g晶型及其制备方法与应用 Download PDF

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WO2020186963A1
WO2020186963A1 PCT/CN2020/076157 CN2020076157W WO2020186963A1 WO 2020186963 A1 WO2020186963 A1 WO 2020186963A1 CN 2020076157 W CN2020076157 W CN 2020076157W WO 2020186963 A1 WO2020186963 A1 WO 2020186963A1
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aconitine
crystal form
preparation
days
solution
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吴琼粉
李彪
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云南昊邦制药有限公司
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    • 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
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/22—Bridged ring systems

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  • the invention relates to the field of medicinal chemistry, in particular to a crystal form of aconitine A and its preparation method and application.
  • oxaconitine is (1 ⁇ , 6 ⁇ , 14 ⁇ , 16 ⁇ ) tetrahydro-8,13,14-triol-20-ethyl-1,6,16-trimethoxy-4-methoxymethyl- 8-Acetoxy-14-(4'-p-methoxybenzyl)-aconitine. It is a diterpene diester alkaloid extracted and isolated from the root tuber of Aconitum georgei Comber, a plant of the genus Aconitum in the Ranunculaceae family, named Crassicauline A. It was later renamed Bulleyaconitine A (T2), which is a known natural compound in plant species, and its structural formula is as follows:
  • aconitine preparations are widely used clinically to treat rheumatoid arthritis (RA), osteoarthritis, myofibritis, neck and shoulder pain, low back pain, cancer pain and chronic pain caused by various reasons.
  • RA rheumatoid arthritis
  • osteoarthritis myofibritis
  • neck and shoulder pain low back pain
  • cancer pain chronic pain caused by various reasons.
  • Drug polymorphism is a common phenomenon in drug development and an important factor affecting drug quality.
  • the same drug with different crystal forms has differences in appearance, solubility, melting point, dissolution, and bioavailability, and may even have significant differences, which will affect the stability, bioavailability and efficacy of the drug.
  • the crystal form of the drug will also affect the quality of the pharmaceutical preparation of the drug, the absorption behavior in the human body, and ultimately affect the therapeutic effect of the preparation in the human body and the benefit ratio of side effects.
  • the in-depth research of aconitine A the research on the crystal form and physicochemical properties of aconitine A is of great significance to the evaluation of the efficacy, quality and safety of aconitine A.
  • the Chinese patent with the application number 201710423005.9 discloses dissolving aconitine A with a C1-4 organic solvent, and the obtained aconidin solution is added dropwise to water, stirring while adding, after the addition, suction filtration, and the filter cake is dried. Obtained the amorphous grass Aconitum. At present, there is no relevant report on the crystalline aconitine.
  • the purpose of the present invention is to provide a new crystal form of aconitine and its preparation method.
  • An object of the present invention is to research, discover and provide the crystalline form G crystal form of aconitine by crystallographic methods.
  • the substantially pure crystal form G provided by the present invention has an X-ray powder diffraction pattern as shown in Figure 1, and its X-ray powder diffraction pattern has a 2 ⁇ value of 7.8 ⁇ 0.2, 8.9 ⁇ 0.2, 13.1 ⁇ 0.2, 14.2 ⁇ 0.2 , 17.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.5 ⁇ 0.2, 23.9 ⁇ 0.2 have obvious characteristic absorption peaks.
  • the characteristic peaks of the X-ray powder diffraction pattern may be between one machine and another machine and between one sample and another sample. There will be slight changes.
  • the value may differ by about 1 unit, or by about 0.8 unit, or by about 0.5 unit, or by about 0.3 unit, or by about 0.1 unit, so the value given cannot be considered For absolute.
  • the values given in the differential scanning calorimetry graph of the above-mentioned crystal forms cannot be regarded as absolute.
  • the invention also provides a method for preparing the crystal form of aconitine A with high purity and no residual solvent.
  • the preparation method of the crystalline form of aconitine A provided by the present invention is that after aconitine A is dissolved in a mixed solution of formic acid and n-heptane, the mixture is stirred at low temperature for 5-30 days, and then the solvent is volatilized at 40-90°C. , The obtained solid is a solid obtained by standing at room temperature for 30-120 days.
  • the volume ratio of formic acid and n-heptane in the preparation method of the crystalline form of aconitine G of the present invention is 10:1 to 1:10.
  • the low temperature in the preparation method of the crystalline form of aconitine G of the present invention is 0-8°C, and the solution should be a clear liquid after the stirring.
  • the concentration of aconitine A in the mixed solution of formic acid and n-heptane of the present invention is 1-1000 mg/ml.
  • the preparation method of the crystalline form of aconitine G of the present invention has a crystal form content of more than 99%, high purity, stable characteristic properties of X-ray powder diffraction spectrum, and good stability to light, humidity and heat.
  • the present invention also provides the application of the crystal form of aconitine A in the preparation of drugs for the prevention and/or treatment of rheumatoid arthritis RA, osteoarthritis, myofibritis, neck and shoulder pain, low back pain or cancer pain.
  • the present invention discloses the preparation method of the aconitine G crystal form and the crystalline form of aconitine A.
  • the X-ray powder diffraction spectrum of the crystal form of the present invention measured by Cu-K ⁇ rays is shown in FIG. 1.
  • the crystalline form of Aconitine A G is prepared by adding Aconitine A to a mixed solution of formic acid and n-heptane to dissolve, stirring at low temperature, and then volatilizing the solvent at high temperature, and the resulting solid is obtained after standing at room temperature.
  • the preparation process is simple, and the obtained crystal form has high purity, which is determined to be the G crystal form after XRD characterization. Stability test of the obtained crystalline form of aconitine A shows that the crystal has good stability to light, humidity and heat.
  • Figure 1 is an XRPD diagram of crystal form G
  • Figure 2 is an HPLC chart of crystal form G
  • Figure 3 shows the XRPD images of different time at room temperature.
  • test method is usually implemented under conventional conditions or conditions recommended by the manufacturer.
  • the XRPD images were collected on PANalytacal Empyrean and X’Pert3 X-ray powder diffraction analyzers. The scanning parameters are shown in Table 1.
  • aconitine A 150 mg was suspended in a mixed solution of 5 ml of formic acid and n-heptane (1:9, v/v) at room temperature and a clear solution was obtained after stirring.
  • the clear solution was still clear after stirring at 5°C for about 13 days Solution, so the clear solution was transferred to 50°C and volatilized for about 2 days to obtain a solid.
  • the solid was transferred to room temperature and left for 60 days to obtain the crystalline form of aconitine G, which was subjected to XRPD test.
  • XRPD diagram is shown in Figure 1.
  • Figure 1 shows the X-ray powder diffraction pattern of the crystalline form of aconitine A.
  • HPLC purity data of crystal form G is shown in Table 2, and the HPLC chart is shown in Fig. 2.
  • 148 mg of aconitine was suspended in a mixed solution of 5 ml of formic acid and n-heptane (1:9, v/v) at room temperature and a clear solution was obtained after stirring.
  • the clear solution was still obtained after stirring for about 13 days at 5°C Solution, so the clear solution is transferred to 50°C to volatilize the solvent to obtain a solid.
  • the sample is tested again by XRPD.
  • a clear solution was obtained after suspending and stirring 1500 mg of aconitine in a mixed solution of 1.5 ml formic acid and n-heptane (1:10, v/v) at room temperature.
  • the clear solution was still clear after stirring at 8°C for about 30 days Solution, so the clear solution was transferred to 60°C to volatilize the solvent to obtain an amorphous sample.
  • the amorphous sample was stored at room temperature, and after 70 days, the sample was subjected to XRPD test again.
  • aconitine A 150 mg was suspended in a mixed solution of 5 ml of formic acid and n-heptane (10:1, v/v) at room temperature and a clear solution was obtained after stirring. The clear solution was still obtained after stirring at 5°C for about 20 days. Therefore, the clear solution is transferred to 80°C to evaporate the solvent to obtain an amorphous sample. The amorphous sample was stored at room temperature, and after 120 days, the sample was subjected to XRPD test again.
  • a clear solution of 15000 mg of aconitine was suspended in a mixed solution of 15 ml of formic acid and n-heptane (10:2, v/v) at room temperature after stirring.
  • the clear solution was still clear after stirring for about 5 days at 4°C Solution, so the clear solution was transferred to 90°C to volatilize the solvent to obtain an amorphous sample.
  • the amorphous sample was stored at room temperature, and after 100 days, the sample was subjected to XRPD test again.
  • aconitine A 150 mg was suspended in a mixed solution of 15 ml of formic acid and n-heptane (10:5, v/v) at room temperature and a clear solution was obtained after stirring. The clear solution was still obtained after stirring at 3°C for about 25 days. Solution, so the clear solution was transferred to 46°C to volatilize the solvent to obtain an amorphous sample. The amorphous sample was stored at room temperature, and after 90 days, the sample was subjected to XRPD test again.
  • aconitine A 1500 mg was suspended in a mixed solution of 30 ml of formic acid and n-heptane (1:10, v/v) at room temperature and a clear solution was obtained after stirring.
  • the clear solution was still obtained after stirring for about 30 days at 8°C Solution, so transfer the clear solution to 40°C to volatilize the solvent to obtain an amorphous sample.
  • the amorphous sample was stored at room temperature, and after 60 days, the sample was subjected to XRPD test again.
  • HPLC results are shown in Table 3. The results show that the chemical purity of the samples have not changed in the selected test conditions; the XRPD results show that the crystal forms of the samples have not changed in the selected test conditions.
  • the crystal form G has good physical and chemical stability.

Abstract

一种草乌甲素G晶型以及草乌甲素G晶型的制备方法。草乌甲素G晶型制备是将草乌甲素加入甲酸与正庚烷的混合溶液溶解后，在低温下搅拌，再在高温挥发溶剂，最后经室温放置后得到的固体物。经XRD的表征，确定为G晶型。

Description

一种草乌甲素G晶型及其制备方法与应用
本申请要求于2019年03月15日提交中国专利局、申请号为201910197751.X、发明名称为“一种草乌甲素G晶型及其制备方法与应用”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明涉及药物化学领域，具体涉及一种草乌甲素G晶型及其制备方法与应用。
背景技术
草乌甲素化学名称为(1α，6α，14α，16β)四氢-8，13，14-三醇-20-乙基-1，6，16-三甲氧基-4-甲氧甲基-8-乙酰氧基-14-(4＇-对甲氧基苯甲酯)-乌头烷。它是从毛莨科乌头属植物——长喙乌头(Aconitum georgei Comber)块根中提取、分离出的一种二萜双酯类生物碱，定名为粗茎乌头碱(Crassicauline A)，后来更名为草乌甲素(Bulleyaconitine A，T2)，属于植物物种中的已知天然化合物，结构式如下：
Figure PCTCN2020076157-appb-000001
目前草乌甲素制剂临床上广泛用于治疗类风湿关节炎(RA)、骨关节炎、肌纤维炎、颈肩痛、腰腿痛、癌性疼痛以及各种原因导致的慢性疼痛。
药物多晶型是药品研发中的常见现象，是影响药品质量的重要因 素。晶型不同的同一药物在外观、溶解度、熔点、溶出度和生物有效性等方面有差别，甚至可能会有显著的不同，因而，会影响药物的稳定性、生物利用度及疗效等。而且药物的晶型还会影响药物的药用制剂的质量、在人体的吸收行为，并最终影响该制剂在人体中产生的治疗效果和副作用的获益比。随着草乌甲素的研究深入，开展草乌甲素晶型、理化性质等研究对于草乌甲素药效、质量、用药安全的评价意义重大。申请号为201710423005.9的中国专利公开了将草乌甲素用C1-4的有机溶剂溶解，得到的草乌甲素溶液滴加至水中，边加边搅拌，加毕，抽滤，滤饼干燥制得无定形草乌甲素。目前还没关于结晶态草乌甲素的相关报道。
发明内容
有鉴于此，本发明目的是提供草乌甲素的新晶型及其制备方法。
本发明的一个目的是通过晶体学的方法，研究、发现并提供了草乌甲素的结晶形式G晶型。
本发明采用国际上公认的X-射线粉末衍射法(XRPD)来研究和表征草乌甲素的结晶形式。测定条件与方法：Cu/K-alpha1(靶)，45KV-40mA(工作电压与电流)，2θ＝3-40(扫描范围)，每步扫描时间(s)为17.8-46.7，扫描步长(2θ)为0.0167-0.0263，
Figure PCTCN2020076157-appb-000002
本发明提供的基本上纯净的G晶型，其X-射线粉末衍射图如图1所示，其X射线粉末衍射图在2θ值为7.8±0.2，8.9±0.2，13.1±0.2，14.2±0.2，17.9±0.2，21.2±0.2，22.5±0.2，23.9±0.2处有明显的特征吸收峰。
值得注意的是，对于以上所述晶型的X-射线粉末衍射图，在一台机器和另一台机器之间以及一个样品和另一个样品之间，X-射线粉末衍射图的特征峰可能会略有变化，其数值可能相差大约1个单位，或者相差大约0.8个单位，或者相差大约0.5个单位，或者相差大约0.3个单位，或者相差大约0.1个单位，因此所给出的数值不能视为 绝对的。同样以上所述晶型的差示扫描量热分析曲线图所给出的数值也不能视为绝对的。
本发明还提供了纯度高且不含残留溶剂的草乌甲素G晶型的制备方法。
本发明提供的所述草乌甲素G晶型的制备方法为草乌甲素加入甲酸与正庚烷的混合溶液溶解后，在低温下搅拌5-30天，再在40-90℃挥发溶剂，所得固体物室温放置30-120天得到的固体物。
本发明所述草乌甲素G晶型的制备方法中所述甲酸与正庚烷的体积比为10:1-1:10。
本发明所述草乌甲素G晶型的制备方法中所述低温为0-8℃，且搅拌结束后溶液应为澄明液体。
优选的，本发明所述草乌甲素在甲酸与正庚烷的混合溶液中的浓度为1-1000mg/ml。
本发明所述草乌甲素G晶型制备方法得到晶型含量大于99％，纯度高，X-射线粉末衍射光谱特征性质稳定，对光、湿、热稳定性良好。
本发明还提供了所述草乌甲素G晶型在制备预防和/或治疗类风湿关节炎RA、骨关节炎、肌纤维炎、颈肩痛、腰腿痛或癌性疼痛药物中的应用。
由上述技术方案可知，本发明公开了草乌甲素G晶型以及草乌甲素G晶型的制备方法。本发明所述晶型使用Cu-Kα射线测量得到的X-射线粉末衍射谱图如图1所示。草乌甲素G晶型制备为，草乌甲素加入甲酸与正庚烷的混合溶液溶解后，在低温下搅拌，再在高温挥发溶剂，所得固体物室温放置后得到的固体物。制备工艺过程简单，且获得的晶型纯度高，经XRD的表征，确定为G晶型。所得草乌甲素G晶型，经稳定性试验，结果表明该晶体对光、湿、热稳定性良好。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍。
图1为晶型G的XRPD图；
图2为晶型G的HPLC图；
图3为室温放置不同时间的XRPD图。
具体实施方式
下面将结合本发明实施例，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
为了进一步理解本发明，下面结合具体实施例对本发明进行详细阐述。下述实施例中，除非另有说明，所述的试验方法通常按照常规条件或制造厂商建议的条件实施。
测试参数
XRPD图在PANalytacal Empyrean和X’Pert3 X射线粉末衍射分析仪上采集，扫描参数如表1所示。
表1 XRPD测试参数
Figure PCTCN2020076157-appb-000003
Figure PCTCN2020076157-appb-000004
实施例1、草乌甲素G晶型的制备和鉴定
草乌甲素150毫克在5毫升甲酸与正庚烷(1:9,v/v)的混合溶液中室温悬浮搅拌后获得澄清溶液，将该澄清溶液在5℃下搅拌约13天后仍获得澄清溶液，故将该澄清溶液转移至50℃下挥发约2天后获得固体物。将该固体物转移至室温放置60天后得到草乌甲素G晶型，对其进行XRPD测试。XRPD图见图1。
结果表明，在衍射角(2θ角)为7.8±0.2，8.9±0.2，13.1±0.2，14.2±0.2，17.9±0.2，21.2±0.2，22.5±0.2，23.9±0.2处有明显的特征吸收峰。
图1为草乌甲素G晶型的X-射线粉末衍射图。
实施例2、草乌甲素G晶型的纯度测定
取实施例1所得草乌甲素G晶型样品，按2015版《中国药典》草乌甲素项下其它生物碱检查方法。照高效液相色谱法(通则0512)测定。色谱条件与***适用性试验用十八烷基硅烷键合硅胶为填充剂；以0.2％三乙胺水溶液(用磷酸调节pH值至3.1±0.1)-乙腈(60:40)为流动相；检测波长为260nm。理论板数按草乌甲素峰计算不低于3000。
取本品适量，加流动相溶解并稀释制成每lml中约含0.2mg的溶液，作为供试品溶液；精密量取适量，用流动相稀释制成每lml中含4μg的溶液，作为对照溶液。照含量测定项下的色谱条件，精密量取对照溶液与供试品溶液各20μl，分别注入液相色谱仪，记录色谱图至主成分峰保留时间的2倍，供试品溶液色谱图中如有杂质峰，各杂质峰面积的和不得大于对照溶液的主峰面积(2.0％)。
晶型G的HPLC纯度数据见表2，HPLC图见图2。
表2晶型G的HPLC纯度数据
# RRT Area％
1 0.85 0.15
2 0.96 0.01
3 0.98 0.04
4 1.00 99.16
5 1.07 0.03
6 1.12 0.10
7 1.14 0.50
由表2可知，用该法制备的草乌甲素晶型G纯度为99％以上。
实施例3、草乌甲素无定型向G晶型的转化
草乌甲素148毫克在5毫升甲酸与正庚烷(1:9,v/v)的混合溶液中室温悬浮搅拌后获得澄清溶液，将该澄清溶液在5℃下搅拌约13天后仍获得澄清溶液，故将该澄清溶液转移至50℃下挥发溶剂得固体物，在室温放置0、5、15、25、30天后，对样品再次进行XRPD测试。
室温放置0、5、15、25天XRPD图见图2，室温放置30天的XRPD图与图1一致。
XRPD结果表明，在50℃下挥发溶剂所得固体为无定型，在室温放置5、15、25天后，仍为无定型，室温放置30天后转化为G晶型。
实施例4、草乌甲素G晶型的制备
草乌甲素10毫克在10毫升甲酸与正庚烷(2:8,v/v)的混合溶液中室温悬浮搅拌后获得澄清溶液，将该澄清溶液在0℃下搅拌约10 天后仍获得澄清溶液，故将该澄清溶液转移至40℃下挥发溶剂得无定形样品。将该无定形样品室温保存，在40天后，对样品再次进行XRPD测试。
XRPD结果表明，该样品的XRPD图与图1一致。
实施例5、草乌甲素G晶型的制备
草乌甲素1500毫克在1.5毫升甲酸与正庚烷(1:10,v/v)的混合溶液中室温悬浮搅拌后获得澄清溶液，将该澄清溶液在8℃下搅拌约30天后仍获得澄清溶液，故将该澄清溶液转移至60℃下挥发溶剂得无定形样品。将该无定形样品室温保存，在70天后，对样品再次进行XRPD测试。
XRPD结果表明，该样品的XRPD图与图1一致。
实施例6、草乌甲素G晶型的制备
草乌甲素150毫克在5毫升甲酸与正庚烷(10:1,v/v)的混合溶液中室温悬浮搅拌后获得澄清溶液，将该澄清溶液在5℃下搅拌约20天后仍获得澄清溶液，故将该澄清溶液转移至80℃下挥发溶剂得无定形样品。将该无定形样品室温保存，在120天后，对样品再次进行XRPD测试。
XRPD结果表明，该样品的XRPD图与图1一致。
实施例7、草乌甲素G晶型的制备
草乌甲素15000毫克在15毫升甲酸与正庚烷(10:2,v/v)的混合溶液中室温悬浮搅拌后获得澄清溶液，将该澄清溶液在4℃下搅拌约5天后仍获得澄清溶液，故将该澄清溶液转移至90℃下挥发溶剂得无定形样品。将该无定形样品室温保存，在100天后，对样品再次进行XRPD测试。
XRPD结果表明，该样品的XRPD图与图1一致。
实施例8、草乌甲素G晶型的制备
草乌甲素150毫克在15毫升甲酸与正庚烷(10:5,v/v)的混合溶液中室温悬浮搅拌后获得澄清溶液，将该澄清溶液在3℃下搅拌约25天后仍获得澄清溶液，故将该澄清溶液转移至46℃下挥发溶剂得无定形样品。将该无定形样品室温保存，在90天后，对样品再次进行XRPD测试。
XRPD结果表明，该样品的XRPD图与图1一致。
实施例9、草乌甲素G晶型的制备
草乌甲素1500毫克在30毫升甲酸与正庚烷(1:10,v/v)的混合溶液中室温悬浮搅拌后获得澄清溶液，将该澄清溶液在8℃下搅拌约30天后仍获得澄清溶液，故将该澄清溶液转移至40℃下挥发溶剂得无定形样品。将该无定形样品室温保存，在60天后，对样品再次进行XRPD测试。
XRPD结果表明，该样品的XRPD图与图1一致。
实施例10、草乌甲素G晶型的稳定性试验
为了评估G晶型的固态稳定性，分别称取适量样品在25℃/60％RH和40℃/75％RH条件下敞口放置1周和1个月，在80℃条件下密封放置24小时。对放置后的样品进行XRPD和HPLC表征，以检测G晶型变化和化学纯度。
HPLC结果见表3，结果表明在所选测试条件中样品的化学纯度均未发生变化；XRPD结果表明在所选测试条件中样品的晶型未发生变化。
表3晶型G的稳定性数据汇总
Figure PCTCN2020076157-appb-000005
结论，晶型G具有良好的物理和化学稳定性。

Claims (6)

  1. 草乌甲素G晶型，其特征在于，其X射线粉末衍射图在2θ值为7.8±0.2，8.9±0.2，13.1±0.2，14.2±0.2，17.9±0.2，21.2±0.2，22.5±0.2，23.9±0.2处有明显的特征吸收峰。
  2. 权利要求1所述的草乌甲素G晶型的制备方法，其特征在于，草乌甲素加入甲酸与正庚烷的混合溶液溶解后，在低温下搅拌5-30天，再在40-90℃挥发溶剂，所得固体室温放置30-120天得到草乌甲素G晶型。
  3. 权利要求2所述的草乌甲素G晶型的制备方法，其特征在于，所述甲酸与正庚烷的体积比为10:1-1:10。
  4. 权利要求2所述的草乌甲素G晶型的制备方法，其特征在于，所述低温为0-8℃，且搅拌结束后溶液应为澄明液体。
  5. 权利要求2所述的草乌甲素G晶型的制备方法，其特征在于，所述草乌甲素在甲酸与正庚烷的混合溶液中的浓度为1-1000mg/ml。
  6. 权利要求1所述草乌甲素G晶型在制备预防和/或治疗类风湿关节炎RA、骨关节炎、肌纤维炎、颈肩痛、腰腿痛或癌性疼痛药物中的应用。
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