Literature DB >> 21588207

Potassium clavulanate.

Kotaro Fujii, Kazuyuki Toyota, Akiko Sekine, Hidehiro Uekusa, Ilma Nugrahani, Sukmadjaja Asyarie, N Sundani Soewandhi, Slamet Ibrahim.   

Abstract

The title salt, K(+)·C(8)H(8)NO(5) (-) [systematic name: potassium (2R,5R,Z)-3-(2-hy-droxy-ethyl-idene)-7-oxo-4-oxa-1-aza-bicyclo-[3.2.0]heptane-2-carb-oxyl-ate], a widely used β-lactam anti-biotic, is usually chemically unstable even in the solid state owing to its tendency to be hydrolysed. In the crystal structure, the potassium cations are arranged along the a axis, forming inter-actions to the carboxyl-ate and hy-droxy groups, resulting in one-dimensional ionic columns. These columns are arranged along the b axis, connected by O-H⋯O hydrogen bonds, forming a layer in the ab plane.

Entities:  

Year:  2010        PMID： 21588207      PMCID： PMC3007583          DOI： 10.1107/S1600536810027984

Source DB:  PubMed          Journal:  Acta Crystallogr Sect E Struct Rep Online        ISSN： 1600-5368


Related literature

For the pharmacological activity of clavulanic acid and potassium clavulanate, see: Bird et al. (1982 ▶); Mayer & Deckwer (1996 ▶); Navarro (2005 ▶). For the hydrolysis properties of clavulanic acid and potassium clavulanate, see: Bersanetti et al. (2005 ▶); Brethauer et al. (2008 ▶); Haginaka et al. (1985 ▶); Hickey et al. (2007 ▶); Saudagar et al. (2008 ▶).

Experimental

Crystal data

K+·C8H8NO5 − M = 237.25 Orthorhombic, a = 4.3453 (6) Å b = 7.8191 (11) Å c = 27.491 (3) Å V = 934.1 (2) Å3 Z = 4 Mo Kα radiation μ = 0.57 mm−1 T = 173 K 0.24 × 0.04 × 0.01 mm

Data collection

Rigaku R-AXIS RAPID IP area-detector diffractometer Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T min = 0.876, T max = 0.994 9047 measured reflections 2138 independent reflections 1433 reflections with I > 2σ(I) R int = 0.088

Refinement

R[F 2 > 2σ(F 2)] = 0.044 wR(F 2) = 0.118 S = 1.12 2138 reflections 137 parameters H-atom parameters constrained Δρmax = 0.52 e Å−3 Δρmin = −0.56 e Å−3 Absolute structure: Flack (1983 ▶), 839 Friedel pairs Flack parameter: −0.05 (9) Data collection: PROCESS-AUTO (Rigaku, 1998 ▶); cell refinement: PROCESS-AUTO; data reduction: PROCESS-AUTO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97. Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810027984/tk2689sup1.cif Structure factors: contains datablocks I. DOI: 10.1107/S1600536810027984/tk2689Isup2.hkl Additional supplementary materials: crystallographic information; 3D view; checkCIF report
K+·C8H8NO5−F(000) = 488
Mr = 237.25Dx = 1.687 Mg m−3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71075 Å
Hall symbol: P 2ac 2abCell parameters from 9047 reflections
a = 4.3453 (6) Åθ = 3.0–27.5°
b = 7.8191 (11) ŵ = 0.57 mm−1
c = 27.491 (3) ÅT = 173 K
V = 934.1 (2) Å3Platet, colorless
Z = 40.24 × 0.04 × 0.01 mm
Rigaku R-AXIS RAPID IP area-detector diffractometer2138 independent reflections
Radiation source: rotating anode, Rigaku UltraX181433 reflections with I > 2σ(I)
graphiteRint = 0.088
ω scanθmax = 27.5°, θmin = 3.0°
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)h = −5→5
Tmin = 0.876, Tmax = 0.994k = −10→10
9047 measured reflectionsl = −35→35
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.044H-atom parameters constrained
wR(F2) = 0.118w = 1/[σ2(Fo2) + (0.0305P)2 + 0.8726P] where P = (Fo2 + 2Fc2)/3
S = 1.12(Δ/σ)max = 0.001
2138 reflectionsΔρmax = 0.52 e Å−3
137 parametersΔρmin = −0.56 e Å−3
0 restraintsAbsolute structure: Flack (1983), 839 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: −0.05 (9)
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.
xyzUiso*/Ueq
C11.2101 (11)0.3967 (6)1.20066 (15)0.0297 (11)
C21.1168 (11)0.5309 (6)1.23813 (13)0.0276 (9)
H2A1.29010.57981.25690.033*
H2B0.94470.49641.25960.033*
C31.0199 (11)0.6369 (6)1.19340 (14)0.0250 (10)
H30.80270.67901.19420.030*
C41.2417 (9)0.5363 (6)1.11851 (13)0.0192 (8)
H41.42730.46111.11630.023*
C51.0676 (9)0.5213 (6)1.06982 (13)0.0201 (8)
C61.3526 (11)0.7148 (5)1.13197 (12)0.0218 (9)
C71.5398 (10)0.8175 (6)1.10754 (14)0.0245 (10)
H71.61690.77521.07750.029*
C81.6419 (11)0.9914 (5)1.12198 (13)0.0269 (9)
H8A1.50561.03821.14760.032*
H8B1.85510.98811.13460.032*
O11.3545 (10)0.2661 (4)1.20053 (11)0.0458 (9)
O21.1415 (8)0.6217 (4)1.03630 (9)0.0258 (7)
O30.8682 (9)0.4058 (4)1.06647 (10)0.0318 (7)
O41.6262 (9)1.0947 (4)1.07905 (10)0.0321 (8)
H4A1.69581.19261.08510.038*
O51.2401 (7)0.7604 (4)1.17783 (9)0.0266 (7)
N11.0715 (8)0.4860 (5)1.16197 (10)0.0242 (8)
K10.6334 (2)0.52404 (13)0.97836 (3)0.0284 (2)
U11U22U33U12U13U23
C10.036 (3)0.027 (2)0.026 (2)−0.001 (2)0.001 (2)0.0026 (19)
C20.029 (2)0.035 (2)0.0185 (16)−0.001 (3)−0.0026 (18)0.0049 (18)
C30.026 (2)0.025 (2)0.024 (2)0.0001 (19)0.0021 (19)0.0033 (18)
C40.0183 (18)0.018 (2)0.0211 (17)−0.0025 (18)−0.0009 (15)0.0023 (17)
C50.017 (2)0.022 (2)0.0214 (17)−0.0007 (18)0.0031 (15)−0.0040 (17)
C60.020 (2)0.028 (2)0.0174 (17)0.001 (2)−0.0018 (18)−0.0019 (16)
C70.027 (2)0.026 (2)0.0204 (18)−0.0043 (19)0.0037 (18)0.0005 (17)
C80.030 (2)0.025 (2)0.0255 (18)−0.003 (2)−0.002 (2)0.0008 (18)
O10.070 (3)0.033 (2)0.0340 (16)0.020 (2)0.006 (2)0.0063 (15)
O20.0265 (16)0.0296 (17)0.0213 (12)−0.0041 (16)−0.0002 (13)0.0045 (12)
O30.0366 (19)0.0304 (17)0.0285 (14)−0.0127 (16)−0.0071 (15)0.0038 (13)
O40.046 (2)0.0201 (15)0.0304 (15)−0.0063 (17)−0.0020 (17)0.0034 (12)
O50.0328 (18)0.0248 (17)0.0221 (13)−0.0045 (13)0.0064 (13)−0.0013 (13)
N10.032 (2)0.0236 (19)0.0174 (14)0.0030 (17)0.0036 (14)0.0043 (14)
K10.0242 (4)0.0362 (5)0.0248 (4)0.0008 (5)−0.0007 (4)0.0031 (4)
C1—O11.199 (6)C7—H70.9500
C1—N11.408 (5)C8—O41.432 (5)
C1—C21.525 (6)C8—H8A0.9900
C2—C31.542 (5)C8—H8B0.9900
C2—H2A0.9900O4—H4A0.8400
C2—H2B0.9900O2—K1i2.773 (3)
C3—O51.425 (5)O2—K1ii2.799 (3)
C3—N11.480 (5)O2—K12.827 (3)
C3—H31.0000O3—K12.786 (3)
C4—N11.459 (5)O4—K1ii2.818 (4)
C4—C61.522 (6)O4—K1iii2.865 (4)
C4—C51.542 (5)O4—H4A0.8400
C4—H41.0000K1—O2iv2.773 (3)
C5—O21.252 (5)K1—O2v2.799 (3)
C5—O31.256 (5)K1—O4v2.818 (4)
C6—C71.325 (6)K1—O4vi2.865 (4)
C6—O51.398 (4)K1—C7v3.198 (4)
C7—C81.485 (6)
O1—C1—N1130.1 (4)C1—N1—C4122.4 (4)
O1—C1—C2136.7 (4)C1—N1—C391.1 (3)
N1—C1—C293.2 (3)C4—N1—C3109.9 (3)
C1—C2—C384.5 (3)O2iv—K1—O382.78 (10)
C1—C2—H2A114.6O2iv—K1—O2v79.62 (9)
C3—C2—H2A114.6O3—K1—O2v116.68 (9)
C1—C2—H2B114.6O2iv—K1—O4v176.73 (10)
C3—C2—H2B114.6O3—K1—O4v95.70 (10)
H2A—C2—H2B111.7O2v—K1—O4v103.64 (9)
O5—C3—N1105.3 (3)O2iv—K1—O2101.77 (9)
O5—C3—C2114.9 (4)O3—K1—O246.69 (9)
N1—C3—C289.7 (3)O2v—K1—O278.70 (9)
O5—C3—H3114.7O4v—K1—O279.11 (9)
N1—C3—H3114.7O2iv—K1—O4vi79.21 (9)
C2—C3—H3114.7O3—K1—O4vi130.76 (10)
N1—C4—C6102.0 (3)O2v—K1—O4vi104.54 (9)
N1—C4—C5116.2 (3)O4v—K1—O4vi99.74 (9)
C6—C4—C5115.9 (3)O2—K1—O4vi176.76 (10)
N1—C4—H4107.4O2iv—K1—C590.29 (9)
C6—C4—H4107.4O3—K1—C523.47 (10)
C5—C4—H4107.4O2v—K1—C596.56 (11)
O2—C5—O3125.0 (3)O4v—K1—C589.41 (10)
O2—C5—C4117.7 (4)O2—K1—C523.45 (9)
O3—C5—C4117.2 (3)O4vi—K1—C5154.16 (10)
O2—C5—K164.0 (2)O2iv—K1—C7v137.98 (11)
O3—C5—K162.1 (2)O3—K1—C7v124.63 (12)
C4—C5—K1171.2 (3)O2v—K1—C7v60.23 (10)
O2—C5—K1i44.8 (2)O4v—K1—C7v45.13 (10)
O3—C5—K1i115.7 (3)O2—K1—C7v83.12 (10)
C4—C5—K1i106.1 (2)O4vi—K1—C7v98.25 (10)
K1—C5—K1i81.24 (8)C5—K1—C7v105.17 (11)
C7—C6—O5121.1 (4)O2iv—K1—C8vi89.53 (10)
C7—C6—C4128.8 (4)O3—K1—C8vi154.09 (11)
O5—C6—C4110.0 (3)O2v—K1—C8vi85.89 (9)
C6—C7—C8127.1 (4)O4v—K1—C8vi90.62 (10)
C6—C7—K1ii105.7 (3)O2—K1—C8vi158.79 (11)
C8—C7—K1ii90.4 (2)O4vi—K1—C8vi23.49 (9)
C6—C7—H7116.5C5—K1—C8vi177.48 (12)
C8—C7—H7116.5C7v—K1—C8vi76.57 (11)
K1ii—C7—H771.9O2iv—K1—C5iv18.57 (9)
O4—C8—C7106.4 (3)O3—K1—C5iv68.43 (10)
O4—C8—K1iii52.9 (2)O2v—K1—C5iv96.76 (10)
C7—C8—K1iii86.5 (2)O4v—K1—C5iv158.42 (10)
O4—C8—K1ii49.2 (2)O2—K1—C5iv98.32 (9)
C7—C8—K1ii64.7 (2)O4vi—K1—C5iv81.62 (9)
K1iii—C8—K1ii76.39 (8)C5—K1—C5iv81.24 (8)
O4—C8—H8A110.5C7v—K1—C5iv156.37 (11)
C7—C8—H8A110.5C8vi—K1—C5iv97.88 (10)
K1iii—C8—H8A160.2O2iv—K1—C8v159.90 (10)
K1ii—C8—H8A101.1O3—K1—C8v115.98 (12)
O4—C8—H8B110.5O2v—K1—C8v85.05 (9)
C7—C8—H8B110.5O4v—K1—C8v22.62 (9)
K1iii—C8—H8B72.8O2—K1—C8v87.75 (10)
K1ii—C8—H8B149.1O4vi—K1—C8v92.28 (10)
H8A—C8—H8B108.6C5—K1—C8v104.40 (10)
C5—O2—K1i116.6 (3)C7v—K1—C8v24.83 (10)
C5—O2—K1ii136.3 (3)C8vi—K1—C8v76.39 (8)
K1i—O2—K1ii101.51 (10)C5iv—K1—C8v173.89 (10)
C5—O2—K192.6 (2)O2iv—K1—K1ii90.24 (7)
K1i—O2—K1101.77 (9)O3—K1—K1ii81.25 (7)
K1ii—O2—K1100.16 (10)O2v—K1—K1ii39.02 (7)
C5—O3—K194.5 (2)O4v—K1—K1ii92.38 (7)
C8—O4—K1ii108.2 (2)O2—K1—K1ii39.68 (6)
C8—O4—K1iii103.6 (3)O4vi—K1—K1ii143.56 (7)
K1ii—O4—K1iii99.74 (9)C5—K1—K1ii58.85 (8)
C8—O4—H4A109.5C7v—K1—K1ii66.94 (8)
K1ii—O4—H4A133.2C8vi—K1—K1ii123.66 (8)
K1iii—O4—H4A97.3C5iv—K1—K1ii99.19 (7)
C6—O5—C3109.4 (3)C8v—K1—K1ii85.90 (8)
O1—C1—C2—C3168.2 (6)C5—O2—K1—O3−6.0 (2)
N1—C1—C2—C3−9.2 (3)K1i—O2—K1—O3111.90 (16)
C1—C2—C3—O5−98.0 (4)K1ii—O2—K1—O3−143.96 (16)
C1—C2—C3—N18.8 (3)C5—O2—K1—O2v138.9 (2)
N1—C4—C5—O2151.2 (4)K1i—O2—K1—O2v−103.25 (11)
C6—C4—C5—O231.4 (5)K1ii—O2—K1—O2v0.89 (9)
N1—C4—C5—O3−30.8 (6)C5—O2—K1—O4v−114.7 (3)
C6—C4—C5—O3−150.6 (4)K1i—O2—K1—O4v3.21 (10)
N1—C4—C5—K152 (2)K1ii—O2—K1—O4v107.35 (10)
C6—C4—C5—K1−67.5 (19)C5—O2—K1—O4vi−45.1 (17)
N1—C4—C5—K1i−161.8 (3)K1i—O2—K1—O4vi72.8 (16)
C6—C4—C5—K1i78.4 (4)K1ii—O2—K1—O4vi177 (45)
N1—C4—C6—C7174.2 (4)K1i—O2—K1—C5117.9 (3)
C5—C4—C6—C7−58.6 (6)K1ii—O2—K1—C5−138.0 (3)
N1—C4—C6—O5−2.6 (4)C5—O2—K1—C7v−160.2 (3)
C5—C4—C6—O5124.7 (4)K1i—O2—K1—C7v−42.33 (11)
O5—C6—C7—C8−3.7 (7)K1ii—O2—K1—C7v61.82 (11)
C4—C6—C7—C8179.9 (4)C5—O2—K1—C8vi−176.9 (3)
O5—C6—C7—K1ii−106.5 (4)K1i—O2—K1—C8vi−59.1 (3)
C4—C6—C7—K1ii77.1 (5)K1ii—O2—K1—C8vi45.1 (3)
C6—C7—C8—O4−137.0 (5)C5—O2—K1—C5iv43.6 (2)
K1ii—C7—C8—O4−26.9 (3)K1i—O2—K1—C5iv161.47 (10)
C6—C7—C8—K1iii173.3 (5)K1ii—O2—K1—C5iv−94.39 (11)
K1ii—C7—C8—K1iii−76.57 (10)C5—O2—K1—C8v−135.7 (3)
C6—C7—C8—K1ii−110.1 (5)K1i—O2—K1—C8v−17.85 (11)
O3—C5—O2—K1i−92.7 (4)K1ii—O2—K1—C8v86.29 (10)
C4—C5—O2—K1i85.1 (4)C5—O2—K1—K1ii138.0 (3)
K1—C5—O2—K1i−104.54 (19)K1i—O2—K1—K1ii−104.15 (11)
O3—C5—O2—K1ii119.4 (4)O2—C5—K1—O2iv−120.1 (3)
C4—C5—O2—K1ii−62.7 (5)O3—C5—K1—O2iv70.9 (3)
K1—C5—O2—K1ii107.6 (3)C4—C5—K1—O2iv−16.8 (18)
K1i—C5—O2—K1ii−147.8 (5)K1i—C5—K1—O2iv−163.73 (9)
O3—C5—O2—K111.8 (5)O2—C5—K1—O3169.1 (4)
C4—C5—O2—K1−170.3 (3)C4—C5—K1—O3−87.6 (18)
K1i—C5—O2—K1104.54 (19)K1i—C5—K1—O3125.4 (3)
O2—C5—O3—K1−12.0 (5)O2—C5—K1—O2v−40.5 (2)
C4—C5—O3—K1170.1 (3)O3—C5—K1—O2v150.5 (3)
K1i—C5—O3—K1−63.5 (2)C4—C5—K1—O2v62.8 (18)
C7—C8—O4—K1ii32.7 (4)K1i—C5—K1—O2v−84.14 (9)
K1iii—C8—O4—K1ii105.23 (18)O2—C5—K1—O4v63.2 (2)
C7—C8—O4—K1iii−72.5 (3)O3—C5—K1—O4v−105.9 (3)
K1ii—C8—O4—K1iii−105.23 (18)C4—C5—K1—O4v166.5 (18)
C7—C6—O5—C3173.7 (4)K1i—C5—K1—O4v19.52 (9)
C4—C6—O5—C3−9.2 (4)O3—C5—K1—O2−169.1 (4)
N1—C3—O5—C616.9 (4)C4—C5—K1—O2103.3 (19)
C2—C3—O5—C6113.9 (4)K1i—C5—K1—O2−43.7 (2)
O1—C1—N1—C4−53.6 (7)O2—C5—K1—O4vi174.7 (2)
C2—C1—N1—C4124.1 (4)O3—C5—K1—O4vi5.7 (4)
O1—C1—N1—C3−168.1 (6)C4—C5—K1—O4vi−82.0 (19)
C2—C1—N1—C39.6 (3)K1i—C5—K1—O4vi131.1 (2)
C6—C4—N1—C1−91.7 (5)O2—C5—K1—C7v20.4 (3)
C5—C4—N1—C1141.3 (4)O3—C5—K1—C7v−148.7 (3)
C6—C4—N1—C313.0 (4)C4—C5—K1—C7v123.7 (18)
C5—C4—N1—C3−114.0 (4)K1i—C5—K1—C7v−23.27 (12)
O5—C3—N1—C1106.3 (3)O2—C5—K1—C8vi154 (2)
C2—C3—N1—C1−9.5 (3)O3—C5—K1—C8vi−15 (2)
O5—C3—N1—C4−18.9 (4)C4—C5—K1—C8vi−103 (3)
C2—C3—N1—C4−134.7 (3)K1i—C5—K1—C8vi110 (2)
C5—O3—K1—O2iv−107.7 (3)O2—C5—K1—C5iv−136.3 (2)
C5—O3—K1—O2v−33.2 (3)O3—C5—K1—C5iv54.6 (3)
C5—O3—K1—O4v75.2 (3)C4—C5—K1—C5iv−33.0 (19)
C5—O3—K1—O26.0 (2)K1i—C5—K1—C5iv180.0
C5—O3—K1—O4vi−176.7 (2)O2—C5—K1—C8v46.1 (3)
C5—O3—K1—C7v37.6 (3)O3—C5—K1—C8v−123.0 (3)
C5—O3—K1—C8vi178.5 (2)C4—C5—K1—C8v149.4 (18)
C5—O3—K1—C5iv−120.0 (3)K1i—C5—K1—C8v2.41 (12)
C5—O3—K1—C8v64.7 (3)O2—C5—K1—K1ii−30.0 (2)
C5—O3—K1—K1ii−16.4 (2)O3—C5—K1—K1ii161.0 (3)
C5—O2—K1—O2iv62.1 (3)C4—C5—K1—K1ii73.4 (18)
K1i—O2—K1—O2iv180.0K1i—C5—K1—K1ii−73.62 (7)
K1ii—O2—K1—O2iv−75.85 (11)
D—H···AD—HH···AD···AD—H···A
O4—H4A···O3vii0.841.902.673 (5)153
Table 1

Selected bond lengths (Å)

O2—K1i2.773 (3)
O2—K1ii2.799 (3)
O2—K12.827 (3)
O3—K12.786 (3)
O4—K1ii2.818 (4)
O4—K1iii2.865 (4)

Symmetry codes: (i) ; (ii) ; (iii) .

Table 2

Hydrogen-bond geometry (Å, °)

D—H⋯AD—HH⋯AD⋯AD—H⋯A
O4—H4A⋯O3iv0.841.902.673 (5)153

Symmetry code: (iv) .

  6 in total

Review 1.  New formulations of amoxicillin/clavulanic acid: a pharmacokinetic and pharmacodynamic review.

Authors:  Amparo Sánchez Navarro
Journal:  Clin Pharmacokinet       Date:  2005       Impact factor: 6.447

2.  A short history of SHELX.

Authors:  George M Sheldrick
Journal:  Acta Crystallogr A       Date:  2007-12-21       Impact factor: 2.290

Review 3.  Clavulanic acid: a review.

Authors:  Parag S Saudagar; Shrikant A Survase; Rekha S Singhal
Journal:  Biotechnol Adv       Date:  2008-03-26       Impact factor: 14.227

4.  Simultaneous production and decomposition of clavulanic acid during Streptomyces clavuligerus cultivations.

Authors:  A F Mayer; W D Deckwer
Journal:  Appl Microbiol Biotechnol       Date:  1996-03       Impact factor: 4.813

5.  Hydrates and solid-state reactivity: a survey of beta-lactam antibiotics.

Authors:  Magali B Hickey; Matthew L Peterson; Eric S Manas; Juan Alvarez; Fredrik Haeffner; Orn Almarsson
Journal:  J Pharm Sci       Date:  2007-05       Impact factor: 3.534

6.  High concentrations of clavulanic acid but not of its degradation products decrease glycerol consumption and oxygen uptake rates in cultures of Streptomyces clavuligerus.

Authors:  Simone Brethauer; Martin Held; Sven Panke
Journal:  Biotechnol Bioeng       Date:  2008-06-15       Impact factor: 4.530
  6 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.