Universidade Federal de Sergipe

Disciplina de Farmacognsia I

Produção de Drogas Vegetais

Profa. Dra. Cristiani Walker

 CONTROLE DE QUALIDADE DA MATÉRIA-
PRIMA VEGETAL

Etapa importante
PRODUÇÃO DA MATÉRIA-PRIMA VEGETAL

A qualidade do produto fitoterápico final depende

da qualidade da matéria-prima vegetal
Rev. Bras. Pl. Med., Campinas, v.17, n.3, p.468-472, 2015.

3
 Problemas relacionados
as plantas e drogas vegetais
• Seleção
• Cultura ou cultivo
• Colheita ou Coleta
• Preparo ou tratamento
• Estabilização
• Secagem
• Conservação
• Embalagem
• Tempo de armazenamento
 Cultura

Fatores que influenciam sobre o conteúdo de princípios

ativos de uma droga
• Temperatura - Tragacanto (goma adraganta)
Plantas com muitos alcaloides,
• Tipo de solo tem que ter solo nitrogenado.
O solo é importante, tem que ser
nitrogenado.

• Umidade Tem planta que precisa de muita umidade

e outras não

• Clima - 3 a 30 graus
• Altitude Pq afeta a pressão atmosferica e a temperatura. Ex. Coca planta

• Estado patológico - infestação de centeio com Claviceps purpurea.


OPEN
Received: 24 July 2018
Accepted: 25 November 2018
Published: xx xx xxxx
www.nature.com/scientificreports
Climatic factors control the
geospatial distribution of active
ingredients in Salvia miltiorrhiza
Bunge in China
Chenlu Zhang1,2, Dongfeng Yang3, Zongsuo Liang1,3, Jingling Liu1, Kaijing Yan4,
Yonghong Zhu4 & Shushen Yang1
Climate change profoundly influences the geospatial distribution of secondary metabolites and causes
the geographical migration of plants. We planted seedlings of the same species in eighteen ecological
regions along a latitudinal gradient in eastern and western China, in order to explore the regulation of
multi-climatic factors on active ingredient accumulation in Salvia miltiorrhiza Bunge. The correlations
between six active ingredient contents and ten climatic factors were investigated to clarify their
relationships. We found that climatic factors not only regulated active ingredient contents but also
markedly influenced their composition and led to a specific geospatial distribution of these active
ingredients in China. The main climatic factors include the air temperature, precipitation, atmospheric
vapour pressure and sunshine duration. Future warming in high-latitude regions could cause continued
northward expansion of planting areas suitable for S. miltiorrhiza. The effect of extreme climatic
conditions on active ingredients should not be overlooked. The findings of this study can help farmers
7
scientifically choose suitable cultivation regions in the future. Furthermore, this study provides an
 Related climatic factors. Data on annual c
Data Sharing Service System27 and Provincial Agr
transplanted in an approximately 1000 square metre region at every site. We collected
factors50included
individual samples
annual withhigh temperature
extreme
the scientific method at each site, divided them into five test samples on average ric pressure (AABP), annualand
(n = 10 within two year), average wind speed
removed the rhizome. Fresh root samples were rapidly cleaned with flowing water, vapourdried in a (AAVP),
pressure ventilated area, average relative h
annual
heated in a stove at a constant temperature of 50 °C, and then crushed into a fine annual
powderaccumulated
that could pass through above 10 °C (AA
temperature
65 mesh. 2013 (Table 2). Climate factors were averaged over
Voucher specimens from all populations were identified by Professor Yuejin Zhang of Northwest A&F
University through comparison with herbarium specimens of S. miltiorrhiza located Chromatographic detection
at Northwest Agriculture & analysis by re
Forestry University (WUK381982-5143). The seedlings were obtained from the phy Good (RP-HPLC). RA, SAB,
Agriculture Practice DTS, CTS, TSI, and
pro-
duction base belonging to Shaanxi Tasly Plant Pharmaceutical Co. Ltd. (ShangluoThe sum
City, of RAProvince,
Shaanxi and SAB China),
defined the total phenolic
which has been authenticated three times by China’s Food and Drug Administration. total tanshinone (TTS). The effectiveness, linearit
were confirmed to be sufficient. The results of ch
Related climatic factors. Data on annual climatic factors were obtained Pharmacy Engineering
from the China (Northwest Agriculture &
Meteorological
Data Sharing Service System and Provincial Agricultural Meteorological Service Center. The 10 main climatic
27

factors included annual extreme high temperature (AEHT), annual precipitationStatistical

(AP), annualanalysis. The results are presen
average baromet-
ric pressure (AABP), annual average wind speed (AAWS), annual average temperature (AAT), annual averageand Duncan’s mul
analysed by one-way ANOVA
vapour pressure (AAVP), annual average relative humidity (AARH), annual average Statistical
lowestsignificance
temperaturewas considered as P < 0.05.
(AALT),
annual accumulated temperature above 10 °C (AAT ≥ 10), and annual sunshine ponent analysis
duration (PCA),
(ASD) from and stepwise
2012 to multiple linea
2013 (Table 2). Climate factors were averaged over two years. Statistics 23 software 18
. The complex relationships
intuitively displayed by a heat map using HemI 1.0
Chromatographic detection analysis by reverse-phase high-performance liquid chromatogra-
phy (RP-HPLC). RA, SAB, DTS, CTS, TSI, and TSIIA were determined by HPLC Results
as described by Peng L et al.25.
The sum of RA and SAB defined the total phenolic acid (TPA), and the sum of CTS, TSI, anddistribution
Geospatial TSIIA definedcharacteristics
the of
total tanshinone (TTS). The effectiveness, linearity, repeatability, precision, andrrhiza grown
stability in the
of the 18 test
HPLC sites are shown in Figs
method
eastern and western
were confirmed to be sufficient. The results of chromatographic analysis were obtained from the Institute of sites. The change in single-co
Pharmacy Engineering (Northwest Agriculture & Forestry University, Yangling, component
China). contents. With a decrease in latitude, t
a single peak in the western sites. Although the va
Statistical analysis. The results are presented as the mean ± standard western deviation sites, the The
(SD). average
dataTTS content was similar
were
analysed by one-way ANOVA and Duncan’s multiple comparison test using IBM titude andStatistics
SPSS mid-latitude sites were evidently higher
23 software.
Statistical significance was considered as P < 0.05. Pearson’s two-tailed correlation analysis (CA), principal com-
ponent analysis (PCA), and stepwise multiple linear regression (SMLR) analysis were performed using IBM SPSS
Statistics 23 software18. The complex relationships between ecological factors and active ingredient contents were
SCIENTIFIC28REPORTS | (2019) 9:904 | DOI:10.1038/s41598-018-36729-x
intuitively displayed by a heat map using HemI 1.0 software .

Results 8
Geospatial distribution characteristics of tanshinones. The active ingredient contents of S. miltio-
17 KM 30.9 862 809 2.8 15.1 12.6 70.8 11.5 5,320 2,354
18 WS 31.8 923 844 3.5 16.4 14.4 Related
77.6 climatic
12.8 5,780factors.
2,050 Data on annual clim
Data Sharing Service System27 and Provincial Agricu
Table 2. Climatic factors examined in this study. Data were obtained factors
from theincluded annual extreme
China Meteorological Data high temperature (A
ric pressure
Sharing Service System and Provincial Agricultural Meteorological Service (AABP), annual
Center. Abbreviations: AEHT-average wind speed (A
vapour pressure (AAVP),
annual extreme high temperature, AP-annual precipitation, AABP-annual average barometric pressure, annual average relative hum
AAWS-
annualaverage
annual average wind speed, AAT-annual average temperature, AAVP-annual accumulated
atmospherictemperature
vapour above 10 °C (AAT
2013 (Table
pressure, AARH-annual average atmospheric relative humidity, AALT-annual 2).lowest
average Climate factors were averaged over tw
temperature,
ACT ≥ 10-annual cumulative temperature above 10 °C, ASD-annual sunshine duration.
Chromatographic detection analysis by reve
phy (RP-HPLC). RA, SAB, DTS, CTS, TSI, and TS
The sum of RA and SAB defined the total phenolic a
total tanshinone (TTS). The effectiveness, linearity,
were confirmed to be sufficient. The results of chro
Pharmacy Engineering (Northwest Agriculture & Fo

Statistical analysis. The results are presente

analysed by one-way ANOVA and Duncan’s multip
Statistical significance was considered as P < 0.05. Pe
ponent analysis (PCA), and stepwise multiple linear r
Statistics 23 software18. The complex relationships be
intuitively displayed by a heat map using HemI 1.0 so

Results
Geospatial
Figure 2. Active ingredient contents of S. miltiorrhiza in the eastern sites. distribution
The SAB content is presented characteristics
on the of ta
right Y axis, and the other ingredient contents are presented on the leftrrhiza
Y axis. grown
For eachin
location, values with
the 18 test sites are shown in Figs 2
different letters are significantly different according to Duncan’s test (Peastern
< 0.05), n = 10,
and mean ± sites.
western SD. This figure
The change in single-com
was created using OriginPro 8 software. RA-rosmarinic acid, SAB-salvianolic acid B, DTS-dihydrotanshinone,
CTS-cryptotanshinone, TSI-tanshinone I, TSIIA-tanshinone IIA. component contents. With a decrease in latitude, the
a single peak in the western sites. Although the vari
western sites, the average TTS content was similar be
titude and mid-latitude sites were evidently higher th
In addition, the TPA/TTS proportion generally increased with increasing ASD in the eastern and western
sites, especially in the western sites. The TPA/TTS proportion decreased with an increase in air temperature
and the AAVP. The TPA/TTS proportion showed a significant negative correlation with the AEHT and AALT
(P < 0.05) in the eastern sites and with the AAVP, AARH, and AABP (P < 0.05) in the western sites. The TPA/TTS
proportion increased with latitudeSCIENTIFIC REPORTS
and elevation |
(Fig. 7). These (2019) 9:904 | DOI:10.1038/s41598-018-36729-x
results indicated that the TPA/TTS proportion
would increase under low-temperature stress, water stress, or an excessive ASD.

Stepwise multiple linear regression (SMLR) analysis. SMLR has been applied to identify the best 9
prediction model in many studies. The standardized regression coefficient reveals the significance of an individ-
 Colheita ou Coleta

MANUAL MECANIZADA

Pesquisa
Colheita é mecanizada

DEPENDE DO MATERIAL A SER COLETADO

 Coleta

Fatores que influenciam no teor e conteúdo de

princípios ativos
• Órgão para órgão (Chamomilla recutita) A depender a planta o oleo
essencial estara presente
em uma parte mais que

• Idade da planta Planta velha não pode a não ser a camelia serenses outra.

• Estado patológico
• Período do dia em que é feita a
coletaTem que ser ao amanhecer, não pode coletar meio dia

• Época da coleta
 Coleta

Órgão Época de colheita

Raízes e rizomas Primavera e/ou
Outono
Cascas Primavera
Folhas Durante o dia
Flores Polinização
Sementes Antes da deiscência

Oliveira, 2001
 PROPORÇÃO PERCENTUAL RELATIVA ENTRE
ESCOPOLAMINA E ATROPINA
NAS FRAÇÕES DE ALCALÓIDES TOTAIS.

Proporção Percentual entre Escopolamina e Atropina

FOLHA CAULE
MÊS
Escopolamina Atropina Escopolamina Atropina
1 61,7 38,3 69,3 30,7

2 65,9 34,1 48,4 51,6

3 67.9 32,1 63,0 37,0
4 71,0 29,0 79,0 21,0
5 70,0 30,0 76,0 24,0
6 66,6 33,4 76,0 24,0
7 68,3 31,7 86,6 13,4
8 78,2 21,8 86,5 13,5
9 66,2 33,8 76,6 23,4

10 47,3 52,7 24,6

11 57,8 42,2 73,4 26,6

12 58,2 41,8 73,8 "26,2

Tab. 2.5 - Variação alcaloídica de Datura suaveolens Humboldt et Bonpland durante um ano.

13

13
 Preparo ou tratamento

• Lavagem
• Seleção
NÃO UTILIZAR
- Exemplares com manchas
- Perfurados por insetos
- Com terra
- Fora do padrão
 Estabilização

Quando for secar a planta depois do periodo estabelecido, tem que fazer a estabilização até a secagem

Impede a ação enzimática

Alteração dos compostos químicos presentes na

droga
Desnaturação protéica das enzimas celulares

Destruição das suas estruturas quaternária e terciária

 Formas de estabilização

• Aquecimento: 80°C, 15-30 minutos 80 graus diminui o teor de principio

ativo, por isso só pode de 15-30 minutos.

• Solvente: imersão do material vegetal em

etanol em ebulição

• Irradiação UV: poder de penetração dos raios

UV é pequeno
 Secagem

• Eliminar certa quantidade de água do órgão

vegetal

• Diminuição do volume da droga

• Facilita a conservação da droga

• Evita a contaminação por micro-organismos

 Secagem

% DE ÁGUA NECESSÁRIA PARA A AÇÃO DE AGENTES DELETÉRIOS

Agentes % de umidade
Bactérias 40 a 45
Enzimas 20 a 25
Fungos 15 a 20

* Quanto maior o teor de água, a droga fica mais sujeita a

agentes deletérios
Oliveira, 2001
 Secagem

• Processos naturais
- Secagem á sombra
- Secagem ao sol
- Secagem mista

• Processos artificiais
- Circulação de ar
- Aquecimento
- Vácuo
- Esfriamento
 Processos naturais

• Secagem à sombra
- Processo lento
- Pode facilitar a decomposição da droga
- Presença de enzimas
 Processos naturais

• Secagem ao sol
- Processo rápido
- Cuidar: componentes voláteis ou princípios
termolábeis
• Secagem mista
- Diminui o tempo de secagem sem alterar o teor
de princípios ativos
 Processos artificiais

• Circulação de ar: passagem de ar com velocidade

adequada. Drogas com princípios termolábeis
• Aquecimento: estufa sem circulação de ar com
temperatura controlada (35 a 40°C).
 Processos artificiais

• Aquecimento com passagem de ar: diminui o

tempo dse operação. Drogas com princípios
ativos voláteis
• Liofilização: congela-se o material e retira-se a
água à vácuo por sublimação
 Conservação
Fatores que interferem a conservação da
droga:

*Ambiente

*Estado de divisão

*Embalagem

*Tempo de armazenamento
 Ambiente
• Alvenaria com bom arejamento
• Janelas e portas programadas para
impedir a entrada de insetos e
roedores
• Iluminação pouco intensa
• Temperatura ideal: 5-15°C
 Estado de divisão
• Reduz o material vegetal a
fragmentos de pequenas dimensões
• Quanto mais dividida a droga:
- Absorção de mais umidade
- Aceleração de processos oxidativos
- Perda de substâncias voláteis
 Embalagem
• Depende da droga
• Deve permitir trocas gasosas
• Não pode reagir com as substâncias
contidas na droga
- Óleos voláteis e óleo fixos reagem
com embalagens plásticas
 Embalagem
• Drogas que se deterioram com
facilidade
- Digitalis e Esporão do Centeio
- Embaladas em latas
• Gomas, resinas e extratos
- Barris ou caixas
 Embalagem
• Em farmácias e laboratórios pequenos:
frascos de vidro âmbar hermeticamente
fechados
• F. Bras. IV: as drogas devem ser
acondicionadas em recipiente de vidro
bem fechado ao abrigo da luz e do calor,
por período não superior a 1 ano,
dependendo da droga
Tempo de armazenamento
• Máximo por um 1 ano
• Exceção: Cáscara-sagrada
• Armazenada por 1 ano ou aquecimento à
100°C por 1-2 h
• Redução do teor de antronas irritação
da mucosa gástrica, vômitos, cólicas e
diarreia sanguinolenta